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Sample records for rheumatoid arthritis a role

  1. 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 ...

  2. Rheumatoid Arthritis

    MedlinePlus

    ... Rheumatoid Arthritis What Is Rheumatoid Arthritis? An Inflammatory, Autoimmune Disease Rheumatoid arthritis is an inflammatory disease that causes ... sometimes feverish. Rheumatoid arthritis is classified as an autoimmune disease. An autoimmune disease occurs when the immune system ...

  3. Role of immunity to mycobacterial stress proteins in rheumatoid arthritis.

    PubMed Central

    McLean, L.; Winrow, V.; Blake, D.

    1990-01-01

    'Stress Proteins in Inflammation' provided a forum for the discussion of topical issues in this rapidly moving field. The mycobacterial 65 kDa stress proteins play a key role in certain animal models of inflammatory arthritis. However, the impression emerging is that the mechanism probably involves more than a simple cross-reaction between mycobacterial SP65 and either the host SP65 or a cartilage antigen, and that evidence for a primary role in human rheumatoid arthritis is lacking. A realistic role for immune responses against stress proteins might be the amplification or perpetuation of inflammation. If so, this is unlikely to be limited to arthritis. PMID:2184873

  4. What Is Rheumatoid Arthritis?

    MedlinePlus

    ... Information Arthritis Find a Clinical Trial Journal Articles Rheumatoid Arthritis PDF Version Size: 57 KB Audio Version Time: ... Size: 9.7 MB November 2014 What Is Rheumatoid Arthritis? Fast Facts: An Easy-to-Read Series of ...

  5. Rheumatoid Arthritis and the Cervical Spine: A Review on the Role of Surgery

    PubMed Central

    Gillick, John L.; Wainwright, John; Das, Kaushik

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease affecting a significant percentage of the population. The cervical spine is often affected in this disease and can present in the form of atlantoaxial instability (AAI), cranial settling (CS), or subaxial subluxation (SAS). Patients may present with symptoms and disability secondary to these entities but may also be neurologically intact. Cervical spine involvement in RA can pose a challenge to the clinician and the appropriate role of surgical intervention is controversial. The aim of this paper is to describe the pathology, pathophysiology, clinical manifestations, and diagnostic evaluation of rheumatoid arthritis in the cervical spine in order to provide a better understanding of the indications and options for surgery. Both the medical and surgical treatment options for RA have improved, so has the prognosis of the cervical spine disease. With the advent of disease modifying antirheumatic drugs (DMARDs), fewer patients are presenting with cervical spine manifestations of RA; however, those that do, now have improved surgical techniques available to them. We hope that, by reading this paper, the clinician is able to better evaluate patients with RA in the cervical spine and determine in which patients surgery is indicated. PMID:26351458

  6. 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 ...

  7. Role of Leukotriene B4 Receptors in Rheumatoid Arthritis

    PubMed Central

    Mathis, Steven; Jala, Venkatakrishna R.; Haribabu, Bodduluri

    2007-01-01

    The purpose of this review is to summarize the role that murine models of arthritis are playing in the understanding of human rheumatoid arthritis and how leukotriene B4 (LTB4) is emerging as an important target in this field. Both the collagen-induced arthritis (CIA) model and the K/BxN serum transfer arthritis model have contributed to outline the potential mechanisms involved in inflammatory arthritis. Indeed, the CIA model has contributed to the development of effective anti-TNF and anti-IL-1β based treatments for RA that are currently in the clinic. Many recent studies in mouse models have suggested a critical role for LTB4 and its receptors in the development of inflammatory arthritis. Inhibitors of LTB4 biosynthesis as well as LTB4 receptors are protective in mouse models of RA and mice deficient in the LTB4 biosynthetic enzymes or LTB4 receptors are resistant to disease development suggesting several promising targets for RA in this pathway. PMID:17967719

  8. Rheumatoid arthritis

    MedlinePlus

    ... rheumatoid arthritis drugs. However, because they are very expensive, insurance approval is generally required. Most of them ... rich in fish oils (omega-3 fatty acids). Smoking cigarettes should be stopped. Excessive alcohol should also ...

  9. 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. PMID:17225486

  10. MRI appearance of retrocalcaneal bursitis and rheumatoid nodule in a patient with rheumatoid arthritis.

    PubMed

    Mutlu, Hakan; Sildiroglu, Huseyin; Pekkafali, Zekai; Kizilkaya, Esref; Cermik, Hakan

    2006-09-01

    Rheumatoid arthritis is an autoimmune disorder of unknown etiology characterized by symmetric, erosive synovitis and sometimes multisystem involvement. Rheumatoid nodules have been reported in as many as 20-30% of patients with rheumatoid arthritis; however, they are not commonly seen in the feet. We present magnetic resonance (MR) findings of a rarely seen case of rheumatoid bursitis in the retrocalcaneal bursa associated with a subcutaneous rheumatoid nodule inferior to the calcaneus which histologically confirmed the rheumatoid arthritis. To the best of our knowledge, this is the first case that rheumatoid bursitis in the retrocalcaneal bursa associated with the rheumatoid nodule in the foot was revealed by MR imaging. PMID:16222409

  11. Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis

    PubMed Central

    Nguyen, Nam Trung; Nakahama, Taisuke; Nguyen, Chi Hung; Tran, Trang Thu; Le, Van Son; Chu, Hoang Ha; Kishimoto, Tadamitsu

    2015-01-01

    Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen-induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes. Consistent with these findings, several Ahr antagonists such as α-naphthoflavone, resveratrol, and GNF351 reverse the effect of Ahr ligands in RA pathogenesis. In this review, we summarize the current knowledge of Ahr function in the immune system and the potential clinical benefits of Ahr antagonism in treating RA. PMID:27186143

  12. Is yoga a suitable treatment for rheumatoid arthritis: current opinion.

    PubMed

    Telles, Shirley; Singh, Nilkamal

    2012-01-01

    We reviewed published literature regarding the use of yoga for managing rheumatoid arthritis to determine whether adequate evidence exists to suggest its usefulness as a therapy. A search for previous studies involving yoga and rheumatoid arthritis in PubMed yielded eight reports. These studies reported the benefits of yoga in the physical and mental health of patients with rheumatoid arthritis (RA), suggesting that yoga is a useful add-on therapy for RA patients. However, all studies showed limitations with respect to sample size, study design, description and duration of yoga intervention, and assessment tools and statistical methods used. Additionally, the studies did not attempt to understand the mechanisms underlying observed benefits. Hence, evidence suggests a definite role of yoga in RA improvement, reducing pain, improving function, and creating a positive mental state. However, detailed analysis and additional studies are necessary to verify these observations. PMID:24198591

  13. 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. PMID:26178249

  14. Genetics of rheumatoid arthritis - a comprehensive review.

    PubMed

    Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T; Mikecz, Katalin; Szekanecz, Zoltán

    2013-10-01

    The "Bermuda triangle" of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11-37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci - Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively - have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics. PMID:23288628

  15. Towards a stratified targeted approach with biologic treatments in rheumatoid arthritis: role of synovial pathobiology.

    PubMed

    Astorri, Elisa; Nerviani, Alessandra; Bombardieri, Michele; Pitzalis, Costantino

    2015-01-01

    Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disease affecting diarthrodial joints and extra-articular tissues; in the absence of an effective treatment, it is characterized by persistent symmetrical and erosive synovitis which leads to structural joint damage and lifelong disability. Several autoantibodies have been associated with RA such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). B cells have been shown to play a crucial role in the pathogenesis of RA by producing autoantibodies and promoting synovial inflammation through antigen presentation, T cells activation and cytokines production [1]. Although biologic agents have notably improved disease outcome and patients' quality of life, currently around 30-40% of subjects do not respond to treatment and the mechanisms leading to resistance are still not known [2]. For this reason, new prognostic biomarkers and predictors of response are needed. We and others have postulated that the development of biomarkers for patients' stratification prior therapeutic intervention may be possible through a better understanding of the different histopathological patterns present both in early and established individual RA patient and the related underlying cellular and molecular mechanisms. To date, Tumor Necrosis Factor (TNF)-α has been shown to be one of the master elements of inflammation in RA; however, even though therapies aimed at blocking this key cytokine have emerged as a major tool in the treatment of RA, a large proportion of patients (approximately 30-40%) do not achieve a meaningful clinical response assessed by either the American College of Rheumatology (ACR) or the European League Against Rheumatism (EULAR) criteria. The same limitation can be applied to the use of rituximab, a chimeric monoclonal antibody directed against CD20, which is uniquely expressed by all B-lymphocytes during the maturation process from late stage pro-B cells to memory cells. The

  16. Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases. Perspectives and therapeutic aspects.

    PubMed

    Harifi, Ghita; Sibilia, Jean

    2016-04-01

    Well-recognized for their role in vascular homoeostasis, platelets may play a major role in inflammation and immunomodulation. Substantial data are emerging on the pathogenic involvement of platelets in inflammatory arthritis and autoimmune diseases, indicating the existence of crosstalk between the coagulation and inflammation system. Upon activation, platelets release pro-inflammatory platelets microparticles, which interact with leucocytes leading to joint and systemic inflammation in rheumatoid arthritis. Platelets activation by immune complexes activate dendritic cells promoting the secretion of interferon alpha, which has a key role in the development of systemic lupus erythematous. In this review, we discuss the current data on the role of platelets in the pathophysiology of inflammatory arthritis and various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. PMID:27052277

  17. Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases

    PubMed Central

    Harifi, Ghita; Sibilia, Jean

    2016-01-01

    Well-recognized for their role in vascular homoeostasis, platelets may play a major role in inflammation and immunomodulation. Substantial data are emerging on the pathogenic involvement of platelets in inflammatory arthritis and autoimmune diseases, indicating the existence of crosstalk between the coagulation and inflammation system. Upon activation, platelets release pro-inflammatory platelets microparticles, which interact with leucocytes leading to joint and systemic inflammation in rheumatoid arthritis. Platelets activation by immune complexes activate dendritic cells promoting the secretion of interferon alpha, which has a key role in the development of systemic lupus erythematous. In this review, we discuss the current data on the role of platelets in the pathophysiology of inflammatory arthritis and various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. PMID:27052277

  18. 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

  19. 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.

  20. Bronchiolitis obliterans organizing pneumonia in a patient with rheumatoid arthritis.

    PubMed

    Pommepuy, I; Farny, M; Billey, T; Olivier, P; Lassoued, S

    1998-01-01

    A 75-year old man with rheumatoid arthritis developed bronchiolitis obliterans organizing pneumonia (BOOP), which responded to treatment with prednisolone (1 mg/kg/d) and cyclophosphamide (100 mg/d). PMID:9523389

  1. Juvenile rheumatoid arthritis

    MedlinePlus

    ... joints. This form of JIA may turn into rheumatoid arthritis. It may involve five or more large and ... no known prevention for JIA. Alternative Names Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ...

  2. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis.

    PubMed

    Gonzalo-Gil, Elena; Galindo-Izquierdo, María

    2014-01-01

    Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis. PMID:24685296

  3. Ultrasound Detection of Salmonella Septic Arthritis in a Rheumatoid Arthritis Patient on Anti-TNF Treatment

    PubMed Central

    Kelly, Stephen

    2014-01-01

    We report a case of Salmonella septic arthritis detected by ultrasound in a 40-year-old man with rheumatoid arthritis while he was on anti–tumor necrosis factor-α monoclonal antibody certolizumab. An aspirate of his left elbow joint showed Salmonella enteritidis infection that was sensitive to ceftraixone. This was preceded by a brief episode of loose stools following a visit to the Far East. He was treated with antibiotics and made a good recovery. There have only been a few case reports of Salmonella septic arthritis in a rheumatoid arthritis patient on anti–tumor necrosis factor treatment but none previously in association with certolizumab. PMID:26425605

  4. Towards an understanding of the role of DNA methylation in rheumatoid arthritis: therapeutic and diagnostic implications

    PubMed Central

    Cribbs, Adam; Feldmann, Marc; Oppermann, Udo

    2015-01-01

    The term ‘epigenetics’ loosely describes DNA-templated processes leading to heritable changes in gene activity and expression, which are independent of the underlying DNA sequence. Epigenetic mechanisms comprise of post-translational modifications of chromatin, methylation of DNA, nucleosome positioning as well as expression of noncoding RNAs. Major advances in understanding the role of DNA methylation in regulating chromatin functions have been made over the past decade, and point to a role of this epigenetic mechanism in human disease. Rheumatoid arthritis (RA) is an autoimmune disorder where altered DNA methylation patterns have been identified in a number of different disease-relevant cell types. However, the contribution of DNA methylation changes to RA disease pathogenesis is at present poorly understood and in need of further investigation. Here we review the current knowledge regarding the role of DNA methylation in rheumatoid arthritis and indicate its potential therapeutic implications. PMID:26425149

  5. Anti-inflammatory functions of Houttuynia cordata Thunb. and its compounds: A perspective on its potential role in rheumatoid arthritis

    PubMed Central

    LI, JUN; ZHAO, FUTAO

    2015-01-01

    The aim of this review was to take a look at the anti-inflammatory functions of Houttuynia cordata Thunb. (HCT) that have been illustrated in the literature and to explore new fields in which HCT could be used in the future. The use of HCT has been described in broad inflammatory domains, where it has exhibited a variety of activities, including antiviral, antibacterial, antiparasitic and immunostimulant activity, with high efficiency, mild features and definite therapeutic effects. The numerous anti-inflammatory functions of HCT have demonstrated that HCT has wide application prospects. New uses of HCT and the full extent of its utilization await further investigation. The basic pathological change of rheumatoid arthritis (RA) is synovial proliferation which leads to joint destruction in the long-term. There are types of drugs that have been used clinically for patients with RA, however, due to their side-effects or high prices their broad usage is limited. A safe and low-cost drug is urgently required to be developed for the clinical usage of patients with RA. Thus, HCT has the potential to be a good candidate in the treatment of rheumatoid arthritis. PMID:26170903

  6. 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. PMID:413361

  7. Experimental Drug for Rheumatoid Arthritis Shows Promise

    MedlinePlus

    ... news/fullstory_158076.html Experimental Drug for Rheumatoid Arthritis Shows Promise Baricitinib helped patients who failed other ... HealthDay News) -- An experimental drug to treat rheumatoid arthritis showed promise in a new six-month trial. ...

  8. Treating Rheumatoid Arthritis: Are Biologic Drugs Right for You?

    MedlinePlus

    Treating Rheumatoid Arthritis: Are Biologic Drugs Right for You? What is rheumatoid arthritis (RA)? Rheumatoid arthritis (RA) is a serious condition. The body’s immune system attacks the lining of ...

  9. Interleukin-34 in rheumatoid arthritis: potential role in clinical therapy

    PubMed Central

    Zhang, Fangze; Ding, Rui; Li, Ping; Ma, Cuili; Song, Ding; Wang, Xuetong; Ma, Tianjiao; Bi, Liqi

    2015-01-01

    Objective: To investigate, whether interleukin (IL)-34 can be used as marker for treatment effectiveness in rheumatoid arthritis (RA). Methods: Serum samples were collected from 35 healthy participants and 83 patients with RA before as well as 4 weeks and 12 weeks after treatment initiation with the tumor necrosis factor α (TNF-α) inhibitor Etanercept. Related clinical data and hand radiograms of the patients were evaluated and serum IL-34, IL-6, IL-8, TNF-α, matrix metalloproteinase-3 (MMP-3) in addition to anti-cyclic citrullinated peptide (CCP) antibody concentrations were measured by ELISA. Results: Serum concentrations of IL-34, IL-6, IL-8, TNF-α, MMP-3 and anti-CCP antibodies were markedly elevated in RA patients compared with controls (P<0.001), significantly decreased during treatment and correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and RA disease activity (P<0.05). IL-34 correlated withIL-6, IL-8, TNF-α, MMP-3 and anti-CCP antibodies in RA patients at baseline (P<0.01) and also with IL-8, MMP-3, IL-6, and DAS28 changes during therapy. Patients in stage III of hand X-ray RA scores had higher IL-34 serum concentrations than in stage II (P<0.05). IL-34 level decreased significantly (P<0.01) starting from 4 weeks after therapy initiation. Conclusions: IL-34 serum concentrations correlated with inflammatory cytokines before and during therapy and were significantly higher in stage III of hand X-ray score patients than in stage II participants. IL-34 might be used both as a biomarker for RA diagnosis and therapy efficiency. PMID:26221333

  10. [Imaging of rheumatoid arthritis: role of MR imaging and CT].

    PubMed

    Sugimoto, Hideharu

    2013-07-01

    An increasing aggressive therapeutic strategy has attracted growing attention to the potentials of MR imaging in the diagnosis, prognostication, and outcome measure of rheumatoid arthritis (RA). In the diagnosis of RA, skeletal destructions are the key to the diagnosis and assessment of long-term prognosis in RA. Marginal bone erosion is still recognized as an important finding in the 2010 RA criteria, and erosions typical of RA are deemed to have prima facie evidence of RA. MR imaging can detect erosions better than radiolography. In this regard, erosions detected by CT are considered to be reference standard to evaluate diagnostic accuracy of erosion in MR imaging and other imaging modalities. Further, to assess therapeutic effect of therapeutic agents involving the control of bone remodeling, CT may be used to evaluate bone formation and improvement of osteoporosis. PMID:23961666

  11. 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. PMID:26758436

  12. [Pyoderma gangrenosum associated with rheumatoid arthritis: a case report].

    PubMed

    Beber, André Avelino Costa; Knob, Cristiane Faccin; Shons, Karen Regina Rosso; Neumaier, Walter; da Silva, João Carlos Nunes; Monticielo, Odirlei André

    2014-01-01

    Pyoderma gangrenosum is a chronic inflammatory dermatosis, which is associated with non-infectious systemic diseases such as rheumatoid arthritis and inflammatory bowel disease. It is more common in adults and may present with four distinct clinical forms, all leading to ulceration of the skin affected. Its diagnosis is clinical and demands exclusion of other causes. Treatment should be performed with local care and systemic therapy. PMID:25627229

  13. [Recent progress of radiology in rheumatoid arthritis: a role of magnetic resonance imaging].

    PubMed

    Sugimoto, Hideharu; Takeda, Akira

    2002-12-01

    Since MR imaging directly visualizes all articular components with excellent contrast resolution, it allows the joint to be viewed as a whole organ. An increasing aggressive therapeutic strategy has attracted growing attention to the potentials of MR imaging in the diagnosis, prognostication, and outcome measure of RA. The introduction of MR imaging into the diagnostic criteria for early RA contributes to more accurate diagnosis in patients suspected of having RA and thus allow an earlier decision to start proper medication. Quantification of inflammatory synovitis by MR imaging can assess treatment outcome in fewer subjects than with traditional measures. We believe MR imaging can be cost-effectively incorporated in the treatment trial. PMID:12510356

  14. Examination of Hearing in a Rheumatoid Arthritis Population: Role of Extended-High-Frequency Audiometry in the Diagnosis of Subclinical Involvement

    PubMed Central

    Lasso de la Vega, Mar; Villarreal, Ithzel Maria; Lopez-Moya, Julio; Garcia-Berrocal, Jose Ramon

    2016-01-01

    Objective. The aim of this study is to analyze the high-frequency hearing levels in patients with rheumatoid arthritis and to determine the relationship between hearing loss, disease duration, and immunological parameters. Materials and Methods. A descriptive cross-sectional study including fifty-three patients with rheumatoid arthritis was performed. The control group consisted of 71 age- and sex-matched patients from the study population (consecutively recruited in Madrid “Area 9,” from January 2010 to February 2011). Both a pure tone audiometry and an extended-high-frequency audiometry were performed. Results. Extended-high-frequency audiometry diagnosed sensorineural hearing loss in 69.8% of the patients which exceeded the results obtained with pure tone audiometry (43% of the patients). This study found significant correlations in patients with sensorineural hearing loss related to age, sex, and serum anti-cardiolipin (aCL) antibody levels. Conclusion. Sensorineural hearing loss must be considered within the clinical context of rheumatoid arthritis. Our results demonstrated that an extended-high-frequency audiometry is a useful audiological test that must be performed within the diagnostic and follow-up testing of patients with rheumatoid arthritis, providing further insight into a disease-modifying treatment or a hearing loss preventive treatment. PMID:27239375

  15. Management of the early and late presentations of rheumatoid arthritis: a survey of Ontario primary care physicians.

    PubMed Central

    Glazier, R H; Dalby, D M; Badley, E M; Hawker, G A; Bell, M J; Buchbinder, R; Lineker, S C

    1996-01-01

    OBJECTIVE: To examine primary care physicians' management of rheumatoid arthritis, ascertain the determinants of management and compare management with that recommended by a current practice panel. DESIGN: Mail survey (self-administered questionnaire). SETTING: Ontario. PARTICIPANTS: A stratified computer-generated random sample of 798 members of the College of Family Physicians of Canada. OUTCOME MEASURES: Proportions of respondents who chose various items in the management of two hypothetical patients, one with early rheumatoid arthritis and one with late rheumatoid arthritis. Scores for investigations, interventions and referrals for each scenario were generated by summing the recommended items chosen by respondents and then dividing by the total number of items recommended in that category. The scores were examined for their association with physician and practice characteristics and physician attitudes. RESULTS: The response rate was 68.3% (529/775 eligible physicians). Recommended investigations were chosen by more than two thirds of the respondents for both scenarios. Referrals to physiotherapy, occupational therapy and rheumatology, all recommended by the panel, were chosen by 206 (38.9%), 72 (13.6%) and 309 (58.4%) physicians respectively for early rheumatoid arthritis. These proportions were significantly higher for late rheumatoid arthritis (p < 0.01). In multiple regression analysis, for early rheumatoid arthritis, internship or residency training in rheumatology was associated with higher investigation and intervention scores, for late rheumatoid arthritis, older physicians had higher intervention scores and female physicians had higher referral scores. CONCLUSIONS: Primary care physicians' investigation of rheumatoid arthritis was in accord with panel recommendations. However, rates of referral to rheumatologists and other health care professionals were very low, especially for the early presentation of rheumatoid arthritis. More exposure to

  16. Rheumatoid Arthritis

    MedlinePlus

    ... cold treatment. However, you should not use these methods if you have poor circulation. What can I do? Exercise regularly. Lose weight if you are overweight. Eat a healthy diet. Use heat to reduce pain and stiffness (such as a hot shower or a heating ...

  17. Rheumatoid arthritis

    MedlinePlus

    ... that is often combined with methotrexate and hydroxychloroquine (triple therapy). These drugs may have serious side effects, ... treatment with a three-drug combination known as "triple therapy", or with the biologic drugs, can decrease ...

  18. Genetics of Rheumatoid ArthritisA Comprehensive Review

    PubMed Central

    Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T.; Mikecz, Katalin

    2013-01-01

    The “Bermuda triangle” of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11–37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci — Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively — have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics. PMID:23288628

  19. Microbial Infection and Rheumatoid Arthritis

    PubMed Central

    Li, Song; Yu, Yangsheng; Yue, Yinshi; Zhang, Zhixin; Su, Kaihong

    2014-01-01

    Rheumatoid arthritis (RA) is a complex autoimmune disease affecting 1–2% of general worldwide population. The etiopathogenesis of RA involves the interplay of multiple genetic risk factors and environmental triggers. Microbial infections are believed to play an important role in the initiation and perpetuation of RA. Recent clinical studies have shown the association of microbial infections with RA. Accumulated studies using animal models have also found that microbial infections can induce and/or exaggerate the symptoms of experimental arthritis. In this review, we have identified the most common microbial infections associated with RA in the literature and summarized the current evidence supporting their pathogenic role in RA. We also discussed the potential mechanisms whereby infection may promote the development of RA, such as generation of neo-autoantigens, induction of loss of tolerance by molecular mimicry, and bystander activation of the immune system. PMID:25133066

  20. Juvenile rheumatoid arthritis with cardiac tamponade.

    PubMed Central

    Majeed, H A; Kvasnicka, J

    1978-01-01

    A 4-year-old girl with seronegative systemic juvenile rheumatoid arthritis developed acute cardiac tamponade. Pericardiocentesis and systemic corticosteroids resulted in complete recovery of the pericardial involvement. This was followed by complete remission of rheumatoid disease. Images PMID:686861

  1. Lipoprotein (a), lipids, and lipoproteins in patients with rheumatoid arthritis.

    PubMed Central

    Rantapää-Dahlqvist, S; Wållberg-Jonsson, S; Dahlén, G

    1991-01-01

    Lipoprotein (a), (Lp(a)), an independent atherogenic factor, was significantly increased in 93 patients with classical, seropositive rheumatoid arthritis of median disease activity. In the patients with Lp(a) concentrations above the upper reference value of 480 mg/l there was a significant correlation between Lp(a) and the concentration of orosomucoid, erythrocyte sedimentation rate, and the platelet count. The plasma concentrations of cholesterol and high density lipoprotein-cholesterol in both male and female patients were significantly lower than in controls. Apolipoprotein B and apolipoprotein AI in the patients correlated significantly with total cholesterol and high density lipoprotein-cholesterol respectively. PMID:1829348

  2. Atherosclerosis and Rheumatoid Arthritis: More Than a Simple Association

    PubMed Central

    Cavagna, Lorenzo; Boffini, Nicola; Cagnotto, Giovanni; Inverardi, Flora; Grosso, Vittorio; Caporali, Roberto

    2012-01-01

    In the last decades a large amount of evidence linked rheumatoid arthritis (RA) to atherosclerosis. In fact, RA patients have an increased risk of cardiovascular events that is not fully explained by other classic cardiovascular risk factors. RA and atherosclerosis may share several common pathomechanisms and inflammation undoubtedly plays a primary role. The proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, involved in the pathogenesis of RA, are also independently predictive of subsequent cardiovascular disease (CVD). In RA, inflammation alters HDL constituents and the concentration of LDL and HDL, thus facilitating atherosclerosis and CVD events. On the other hand, also the increase of oxidative processes, frequently observed in RA, induces atherosclerosis. Interestingly, some genetic polymorphisms associated with RA occurrence enhance atherosclerosis, however, other polymorphisms associated with RA susceptibility do not increase CVD risk. Several other mechanisms may influence atherosclerotic processes in RA. Moreover, atherosclerosis may be directly mediated also by underlying autoimmune processes, and indirectly by the occurrence of metabolic syndrome and impaired physical activity. Finally, the effects of RA therapies on cardiovascular system in general and on atherosclerosis in particular are really wide and different. However, the starting point of every RA treatment is that disease control, or better remission, is the best way we have for the reduction of CVD occurrence. PMID:23024462

  3. Platelet and red blood cell interactions and their role in rheumatoid arthritis.

    PubMed

    Olumuyiwa-Akeredolu, Oore-Ofe O; Pretorius, Etheresia

    2015-12-01

    Cytokines, lymphocytes, platelets and several biomolecules have long been implicated in the pathology of rheumatoid arthritis (RA), and the influences of antibody production and tagging, and cytokine, chemokine and enzyme production at specific rheumatoid joints were thought to be exclusive to the advancement of disease parameters. Another role player in RA is red blood cells (RBCs) which, of late, have been found to be involved in RA pathobiology, as there is a positive correlation between RBC counts and joint pathology, as well as with inflammatory biomarkers in the disease. There is also an association between RBC distribution width and the incidence of myocardial infarction amongst RA patients, and there is a change in the lipid distribution within RBC membranes. Of late, certain RBC-associated factors with previously obscure roles and cell-derived particles thought to be inconsequential to the other constituents of plasma were found to be active biomolecular players. Several of these have been discovered to be present in or originating from RBCs. Their influences have been shown to involve in membrane dynamics that cause structural and functional changes in both platelets and RBCs. RBC-derived microparticles are emerging entities found to play direct roles in immunomodulation via interactions with other plasma cells. These correlations highlight the direct influences of RBCs on exacerbating RA pathology. This review will attempt to shed more light on how RBCs, in the true inflammatory milieu of RA, are playing an even greater role than previously assumed. PMID:26059943

  4. Is Hearing Impairment Associated with Rheumatoid Arthritis? A Review

    PubMed Central

    Emamifar, Amir; Bjoerndal, Kristine; Hansen, Inger M.J.

    2016-01-01

    Background: Rheumatoid arthritis (RA) is a systemic, inflammatory disease that affects 1% of the population. The auditory system may be involved during the course of disease; however the association of RA and hearing impairment has not been clearly defined. Objective: The objective of this review is to evaluate published clinical reports related to hearing impairment in patients with RA. Furthermore, we discuss possible pathologies and associated factors as well as new treatment modalities. Method: A thorough literature search was performed using available databases including Pubmed, Embase, Cochrane and ComDisDome to cover all relative reports. The following keywords were used: hearing loss, hearing difficulties, hearing disorders, hearing impairment, sensorineural hearing loss, conductive hearing loss, mixed hearing loss, autoimmune hearing loss, drug ototoxicity, drug-induced hearing loss, hearing test, audiometry, auditory dysfunction and rheumatoid arthritis. Conclusion: Based on our review it can be postulated that patients with RA are at higher risk of hearing impairment compared to healthy subjects in their course of the disease. The hearing impairment in RA seems to be a multifactorial condition; however the mechanisms of injury, as well as the relative risk factors, are not completely clear. This review can aid to clarify this condition and is a guide for further evaluation. To the best of our knowledge, this is the first review of hearing impairment in RA. PMID:27053970

  5. Pyogenic infection and rheumatoid arthritis.

    PubMed Central

    Rowe, I. F.; Deans, A. C.; Keat, A. C.

    1987-01-01

    Ten episodes of severe pyogenic infection occurring in nine patients with rheumatoid arthritis are reported. There was a wide range of presenting features including pyoarthrosis in 7 episodes. Three cases presented with meningitis, bacterial endocarditis and probable multiple abscesses respectively. Infection was caused by Staphylococcus aureus in 7 episodes and by Staphylococcus epidermidis, Streptococcus pneumoniae and beta-haemolytic Streptococcus in each of one episode. Three infective episodes were fatal. Pyogenic, especially staphylococcal, infection should be considered in patients with rheumatoid arthritis with unexplained illness with or without sudden deterioration in joint symptoms. It is important to recognize and treat infection rapidly. Images Figure 1 Figure 2 PMID:3671222

  6. Leflunomide for rheumatoid arthritis.

    PubMed

    2000-07-01

    Disease-modifying antirheumatic drugs (DMARDs) are given to patients with rheumatoid arthritis (RA) to prevent synovitis, slow destruction of articular cartilage and bone, preserve function and control systemic manifestations of the disease. Recognition that irreversible joint damage often occurs early in RA has led to much prompter use of DMARDs, with sulfasalazine or methotrexate commonly considered the treatment of first choice. Leflunomide (Arava-Aventis) is a new DMARD, licensed for the treatment of adults with active RA. The manufacturer claims that leflunomide has "comparable efficacy to methotrexate and sulphasalazine", with a "faster onset of action", and an "acceptable tolerability profile". Here, we consider the place of leflunomide in the management of patients with RA. PMID:11027115

  7. Smoking and Rheumatoid Arthritis

    PubMed Central

    Chang, Kathleen; Yang, So Min; Kim, Seong Heon; Han, Kyoung Hee; Park, Se Jin; Shin, Jae Il

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs), there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF) therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper. PMID:25479074

  8. Physiotherapy in Rheumatoid Arthritis

    PubMed Central

    Kavuncu, Vural; Evcik, Deniz

    2004-01-01

    Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented. PMID:15266230

  9. [Rheumatoid arthritis and malignancy].

    PubMed

    Kameda, Tomohiro; Dobashi, Hiroaki

    2016-06-01

    Rheumatoid arthritis (RA) is associated with excess mortality. Especially, malignancy is a major cause of mortality. According to previous reports, the overall incidence of malignancies in RA patients has been reported to be comparable or slightly higher than that in general population. The increased incidence of malignant lymphoma and lung cancer has been reported to be consistent in most studies. The use of some csDMARD was also reported as risk factors for malignancy. Recently, MTX associated lymphoproliferative disorder(MTX-LPD) is one of the important complications in RA treatment. We revealed the mean MTX dose was demonstrated to be an independent risk factor regarding MTX-LPD onset in RA patients. This data suggest that the treatment with higher MTX dose promotes LPD onset in Japanese RA patients. PMID:27311195

  10. Physiotherapy in rheumatoid arthritis.

    PubMed

    Kavuncu, Vural; Evcik, Deniz

    2004-01-01

    Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented. PMID:15266230

  11. Spontaneous talar and calcaneal fracture in rheumatoid arthritis: a case report

    PubMed Central

    Spina, Antonio; Clemente, Alberto; Vancini, Chiara; Fejzo, Majlinda; Campioni, Paolo

    2011-01-01

    Rheumatoid arthritis (RA) leads to a progressive weakening of the skeleton which may result in bone fractures. However, spontaneous fractures (exclusive of stress fractures, vertebral collapse, and superficial articular fragmentation) in patients with rheumatoid arthritis have been only occasionally reported in the medical literature. A case of spontaneous talar and calcaneal fracture in rheumatoid arthritis is described. Bone lesions were identified on radiographs, MR images and scintigraphy in a patient with right ankle pain. The absence of episodes of acute trauma, and the presence of acute clinical manifestations should guide the clinical suspicion. PMID:22470803

  12. A study of the effects of pulsed electromagnetic field therapy with respect to serological grouping in rheumatoid arthritis.

    PubMed

    Ganguly, K S; Sarkar, A K; Datta, A K; Rakshit, A

    1998-09-01

    The positive role of pulsed electromagnetic field (PEMF) therapy in rheumatoid arthritis (RA) is known. The differential role of serological status of patients in RA is also well known. This paper presents a study of the differential effects of PEMF therapy on the two serological groups of patients. The responses of the seropositive patients are found to be more subdued. Varying effects of the therapy in alleviating the different symptomatologies indicate that the rheumatoid factor (RF) is more resistant to PEMF. PMID:10063282

  13. Effects of rehabilitation for pain relief in patients with rheumatoid arthritis: a systematic review

    PubMed Central

    Park, Youngju; Chang, Moonyoung

    2016-01-01

    [Purpose] The purpose of this study was to find evidence for the effectiveness of rehabilitation for pain relief in patients with rheumatoid arthritis. [Subjects and Methods] A systematic review was conducted of MEDLINE, The Cochrane Central Register of Controlled Trials (CENTRAL), and OVID, for studies published from July 2005 to July 2015. We extracted data regarding patients, intervention, comparison, and outcomes, and assessed the methodological quality of the data. [Results] Nine randomized controlled trials comparing the effects of pain relief in patients with rheumatoid arthritis were found. [Conclusion] Physical therapy and occupational therapy can reduce pain in rheumatoid arthritis. PMID:26957779

  14. Interleukin-1β and Interleukin-6 in Arthritis Animal Models: Roles in the Early Phase of Transition from Acute to Chronic Inflammation and Relevance for Human Rheumatoid Arthritis

    PubMed Central

    Ferraccioli, Gianfranco; Bracci-Laudiero, Luisa; Alivernini, Stefano; Gremese, Elisa; Tolusso, Barbara; De Benedetti, Fabrizio

    2010-01-01

    Tumor necrosis factor-α (TNF-α) is the major target of the therapeutic approach in rheumatoid arthritis. A key issue in the approach to chronic arthritis is the understanding of the crucial molecules driving the transition from the acute phase to the chronic irreversible phase of the disease. In this review we analyzed five experimental arthritis animal models (antigen-induced arthritis, adjuvant-induced arthritis, streptococcal cell wall arthritis, collagen-induced arthritis and SKG) considered as possible scenarios to facilitate interpretation of the biology of human rheumatoid arthritis. The SKG model is strictly dependent on interleukin (IL)-6. In the other models, IL-1β and IL-6, more than TNF-α, appear to be relevant in driving the transition, which suggests that these should be the targets of an early intervention to stop the course toward the chronic form of the disease. PMID:20683549

  15. [Rheumatoid arthritis and autoimmune hemolysis: B-cell depletion for remission induction in a patient with rheumatoid arthritis and cold agglutinin disease].

    PubMed

    Lehmann, P; Hartung, W; Ehrenstein, B; Schölmerich, J; Fleck, M

    2010-08-01

    Autoimmune hemolysis is a rare complication of systemic rheumatic diseases. We report on a 68-year-old female patient with established, long-standing rheumatoid arthritis, who complained of progressive weakness and worsening of her arthralgia under therapy with leflunomide. Physical and laboratory examination revealed autoimmune hemolysis due to cold agglutinin disease. As hemolysis and arthritis were refractory to steroid treatment, B-cell depletion with rituximab was performed leading to a marked reduction of hemolytic parameters as well as remission of her rheumatoid arthritis. PMID:20213090

  16. The Role of Different Subsets of Regulatory T Cells in Immunopathogenesis of Rheumatoid Arthritis

    PubMed Central

    Gol-Ara, Maryam; Jadidi-Niaragh, Farhad; Sadria, Reza; Azizi, Gholamreza; Mirshafiey, Abbas

    2012-01-01

    Rheumatoid arthritis (RA) is a common autoimmune disease and a systemic inflammatory disease which is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion and hyperplasia of synovial tissues. Considering the role of autoreactive T cells (particularly Th1 and Th17 cells) in pathophysiology of RA, it might be assumed that the regulatory T cells (Tregs) will be able to control the initiation and progression of disease. The frequency, function, and properties of various subsets of Tregs including natural Tregs (nTregs), IL-10-producing type 1 Tregs (Tr1 cells), TGF-β-producing Th3 cells, CD8+ Tregs, and NKT regulatory cells have been investigated in various studies associated with RA and collagen-induced arthritis (CIA) as experimental model of this disease. In this paper, we intend to submit the comprehensive information about the immunobiology of various subsets of Tregs and their roles and function in immunopathophysiology of RA and its animal model, CIA. PMID:23133752

  17. [Early rheumatoid arthritis].

    PubMed

    Babić-Naglić, Durdica

    2008-01-01

    Rheumatoid arthritis (RA) is chronic joint disease which if untreated leads to permanent structural damage and disability. Early diagnosis and therapy are the main requests for good clinical practice. Early diagnosis tools include specific clinical assesment, serological, immunogenetic and radiological evaluation. Disease activity score is cornerstone in clinical assesment, rheumatoid factor and anti-cyclic citrullinated peptide antibodies (anti-CCP) are very specific serological parameters. The shared epitope containing HLA-DRB1* alleles represent the most significant genetic risk for RA. Magnetic resonance and ultrasound imaging are very sensitive methods in early phase of disease. PMID:19024271

  18. Medicines to Treat Rheumatoid Arthritis

    MedlinePlus

    ... and 55, but it can happen at any age. Rheumatoid arthritis affects women more than men. Visit your doctor to talk about your health and the medicines you may need. This factsheet will give you information about a type of medicine. You will learn ...

  19. Balneotherapy in rheumatoid arthritis-a systematic review.

    PubMed

    Santos, Isabel; Cantista, Pedro; Vasconcelos, Carlos

    2016-08-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent inflammation of synovial joints with pain, often leading to joint destruction and disability, and despite intensive research, the cause of RA remains unknown. Balneotherapy-also called mineral baths or spa therapy-uses different types of mineral water compositions like sulphur, radon, carbon dioxin, etc. The role of balneotherapy is on debate; Sukenik wrote that the sulphur mineral water has special proprieties to rheumatologic diseases, including in the course of active inflammatory phases in RA. The aim of this review is to summarize the available evidence on the effects of balneotherapy on patients with rheumatoid arthritis. We have made a systematic search of the articles published from 1980 to 2014 on this topic in PubMed, Scopus, CRD, PEDro, Web of Science and Embase databases. We have followed the method set by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). These that have compared balneotherapy with other therapeutic modalities or with no intervention were considered. The inclusion criteria of these papers were randomized control trial (RCT); languages: English, French, Spanish, Italian and Portuguese; evaluation of efficacy (analysis of outcomes); use of natural mineral water baths; and participants with RA. A total of eight articles documenting RCTs were found and included for full review and critical appraisal involving a total of 496 patients. The studies selected highlighted an important improvement and statistically significant in several clinical parameters, in spite of their heterogeneity between the various studies. One study emphasized an important improvement on functional capacity up to 6 months of follow-up (FU). Some of the studies (std.) reveal an improvement on morning stiffness (5 std.), number of active joints (3 std.), Ritchie index (2 std.) and activities of daily living (2 std.) up to 3 months of FU. Three

  20. Restless legs syndrome as a comorbidity in rheumatoid arthritis.

    PubMed

    Gjevre, John A; Taylor Gjevre, Regina M

    2013-01-01

    Rheumatoid arthritis (RA) is a multisystem disease with a complex immunologic pathophysiology. Likewise, sleep disorders can involve a complicated interplay between the neurologic pathways, immune system, and respiratory system. Recent studies have shown an elevated prevalence of sleep abnormalities in connective tissue disorders compared to the general population. Restless legs syndrome (RLS) may be present in up to 30% of RA patients. These findings may be related to cytokine release and other immunomodulatory responses. TNF- α levels relate to sleep physiology and anti-TNF- α therapy may improve sleep patterns. Most of the patients with this disorder can distinguish their RLS sensations from their arthritic symptoms. RLS is a common comorbidity seen with RA, and prompt recognition and treatment can improve patient quality of life. PMID:23840943

  1. 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.

  2. Rheumatoid Arthritis Educational Video Series

    MedlinePlus Videos and Cool Tools

    ... to take a more active role in your care. The information in these videos should not take ... She is a critical member of our patient care team. Managing Your Arthritis Managing Your Arthritis Managing ...

  3. Simultaneous thrombosis of multiple coronary arteries in a patient with rheumatoid arthritis

    PubMed Central

    Kalayci, Arzu; Arslan, Erol; Bakar, Salih Murat; Guneri, Mahmut; Dizman, Rafet; Kivanc, Eylem; Karabay, Can Yucel

    2016-01-01

    We present a case of simultaneous coronary thrombosis of the left main, the left anterior descending artery and the right coronary artery in a patient, recently diagnosed with rheumatoid arthritis. PMID:27489603

  4. Simultaneous thrombosis of multiple coronary arteries in a patient with rheumatoid arthritis.

    PubMed

    Kalayci, Arzu; Arslan, Erol; Bakar, Salih Murat; Guneri, Mahmut; Dizman, Rafet; Kivanc, Eylem; Karabay, Can Yucel

    2016-01-01

    We present a case of simultaneous coronary thrombosis of the left main, the left anterior descending artery and the right coronary artery in a patient, recently diagnosed with rheumatoid arthritis. PMID:27489603

  5. Zingiber officinale: A Potential Plant against Rheumatoid Arthritis

    PubMed Central

    Al-Nahain, Abdullah; Jahan, Rownak

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease particularly affecting elderly people which leads to massive bone destruction with consequent inflammation, pain, and debility. Allopathic medicine can provide only symptomatic relief. However, Zingiber officinale is a plant belonging to the Zingiberaceae family, which has traditionally been used for treatment of RA in alternative medicines of many countries. Many of the phytochemical constituents of the rhizomes of this plant have therapeutic benefits including amelioration of RA. This review attempts to list those phytochemical constituents with their reported mechanisms of action. It is concluded that these phytochemicals can form the basis of discovery of new drugs, which not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction. As the development of RA is a complex process, further research should be continued towards elucidating the molecular details leading to RA and drugs that can stop or reverse these processes by phytoconstituents of ginger. PMID:24982806

  6. [Legionella pneumonia after infliximab in a patient with rheumatoid arthritis].

    PubMed

    Giassi, Karina de Souza; Furlanetto, Vilson; Fialho, Sonia; Gomes Ribeiro, Giovana; Pereira, Ivânio Alves

    2014-01-01

    The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients. PMID:25627305

  7. Common Therapy for Rheumatoid Arthritis Reduces Risk of Death

    MedlinePlus

    ... Research 2013 April 2013 (historical) Common Therapy for Rheumatoid Arthritis Reduces Risk of Death Taking methotrexate—a commonly ... reduce the risk of death among patients with rheumatoid arthritis (RA), according to recently-published research in the ...

  8. [Genetics and genomics in rheumatoid arthritis (RA): An update].

    PubMed

    Rodríguez-Elías, Ana Karen; Maldonado-Murillo, Karina; López-Mendoza, Luis Fernando; Ramírez-Bello, Julián

    2016-01-01

    Rheumatoid arthritis is a chronic inflammatory autoimmune disease that affects approximately 0.5-1% of the general population and leads to chronic synovial inflammation, destruction of cartilage and bone, and disability. The heritability of rheumatoid arthritis has been estimated to be about 60%, while the contribution of HLA to heritability has been estimated to be 11-37%. Other genes, such as PTPN22, STAT4, CTLA4, TRAF1, PADI4, IRF5, FCRL3, TNFIP3, TNF-α, miRNAs, CD28, CD40, TYK2, etc., have been associated with susceptibility, severity, activity, and treatment response of rheumatoid arthritis. The aim of this review is to describe the role of gene variants located in immune system genes associated with susceptibility to rheumatoid arthritis. PMID:27160622

  9. PTPome profile of rheumatoid arthritis fibroblast-like synoviocytes: a novel role for SHP-2 as a modulator of invasion and survival

    PubMed Central

    Stanford, Stephanie M.; Maestre, Michael F.; Campbell, Amanda M.; Bartok, Beatrix; Kiosses, William B.; Boyle, David L.; Arnett, Heather A.; Mustelin, Tomas; Firestein, Gary S.; Bottini, Nunzio

    2013-01-01

    OBJECTIVE The fibroblast-like synoviocytes (FLS) in the synovial intimal lining of the joint are key mediators of inflammation and joint destruction in rheumatoid arthritis (RA). In RA, these cells aggressively invade the extracellular matrix, producing cartilage-degrading proteases and inflammatory cytokines. The behavior of FLS is controlled by multiple interconnected signal transduction pathways involving reversible phosphorylation of proteins on tyrosine residues. However, little is known about the role of the protein tyrosine phosphatases (PTPs) in FLS function. The objective of this study was to explore the expression of all the PTP genes (PTPome) in FLS. METHODS A comparative screening was conducted of the expression of the PTPome in FLS from patients with RA or osteoarthritis (OA). The functional effect of a PTP up-regulated in RA, SHP-2, was then analyzed by knock-down using cell-permeable antisense oligonucleotides in RA FLS. RESULTS PTPN11 was over-expressed in RA compared to OA FLS. Knock-down of PTPN11, which encodes SHP-2, using a cell-permeable antisense oligonucleotide, decreased the invasion, migration, adhesion, spreading and survival of RA FLS. Additionally, signaling in response to growth factors and inflammatory cytokines was impaired by the knock-down of SHP-2. RA FLS deficient in SHP-2 displayed decreased activation of focal adhesion kinase and mitogen-activated protein kinases. CONCLUSION These findings indicate a novel role for SHP-2 in mediating human FLS function, and suggest that SHP-2 promotes the invasiveness and survival of RA FLS. Further investigation may reveal SHP-2 to be a candidate therapeutic target for RA. PMID:23335101

  10. Sedentary behaviour in patients with rheumatoid arthritis: A qualitative study

    PubMed Central

    Thomsen, Tanja; Beyer, Nina; Aadahl, Mette; Hetland, Merete L.; Løppenthin, Katrine; Midtgaard, Julie; Esbensen, Bente A.

    2015-01-01

    Background Despite increasing interest in investigating sedentary behaviour (SB) in the general population and in patients with rheumatoid arthritis (RA), there is little documentation of the subjective experiences of SB in patients with RA. This study aimed to examine how patients with RA describe their daily SB. Methods Fifteen patients with RA (10 women and 5 men) from 23 to 73 years of age and with a disease duration ranging from 4 to 27 years were interviewed following a semi-structured interview guide. Data were analysed using the content analysis method described by Graneheim. Results SB appeared in three categories covering: 1) A constant battle between good and bad days; SB could be a consequence of RA in terms of days with pronounced pain and fatigue resulting in many hours of SB. 2) Adaptation to everyday life; living with the unpredictability of RA included constant modification of physical activity level causing increase in SB, especially during periods of disease flare. Prioritizing and planning of SB also functioned as part of self-management strategies. 3) It has nothing to do with my arthritis; for some patients, SB was not related to RA, but simply reflected a way of living independent of the disease. Conclusions SB is perceived, motivated, and performed differently in patients with RA. An individually tailored approach may be essential in understanding and encouraging patients’ motivation towards sustainable change in SB and activity patterns. PMID:26462971

  11. Rapidly progressive aortic valve incompetence in a patient with rheumatoid arthritis.

    PubMed

    Camilleri, J P; Douglas-Jones, A G; Pritchard, M H

    1991-10-01

    A 27-year-old female with seropositive rheumatoid arthritis of onset at age 18 years developed progressive aortic valve incompetence requiring urgent aortic valve replacement. Rheumatoid aortic valve disease may be more rapidly progressive than aortic valve disease from other causes and awareness of this by the monitoring physicians may help to avoid the possible complications. PMID:1913010

  12. Rheumatoid arthritis affecting temporomandibular joint

    PubMed Central

    Sodhi, Amandeep; Naik, Shobha; Pai, Anuradha; Anuradha, Ardra

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory disorder that is characterized by joint inflammation, erosive properties and symmetric multiple joint involvement. Temporomandibular joint (TMJ) is very rare to be affected in the early phase of the disease, thus posing diagnostic challenges for the dentist. Conventional radiographs fail to show the early lesions due to its limitations. More recently cone-beam computed tomography (CBCT) has been found to diagnose the early degenerative changes of TMJ and hence aid in the diagnosis of the lesions more accurately. Our case highlights the involvement of TMJ in RA and the role of advanced imaging (CBCT) in diagnosing the bony changes in the early phase of the disease. PMID:25684928

  13. TRAF1-C5 as a Risk Locus for Rheumatoid ArthritisA Genomewide Study

    PubMed Central

    Plenge, Robert M.; Seielstad, Mark; Padyukov, Leonid; Lee, Annette T.; Remmers, Elaine F.; Ding, Bo; Liew, Anthony; Khalili, Houman; Chandrasekaran, Alamelu; Davies, Leela R.L.; Li, Wentian; Tan, Adrian K.S.; Bonnard, Carine; Ong, Rick T.H.; Thalamuthu, Anbupalam; Pettersson, Sven; Liu, Chunyu; Tian, Chao; Chen, Wei V.; Carulli, John P.; Beckman, Evan M.; Altshuler, David; Alfredsson, Lars; Criswell, Lindsey A.; Amos, Christopher I.; Seldin, Michael F.; Kastner, Daniel L.; Klareskog, Lars; Gregersen, Peter K.

    2009-01-01

    BACKGROUND Rheumatoid arthritis has a complex mode of inheritance. Although HLA-DRB1 and PTPN22 are well-established susceptibility loci, other genes that confer a modest level of risk have been identified recently. We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis. METHODS We genotyped 317,503 single-nucleotide polymorphisms (SNPs) in a combined case-control study of 1522 case subjects with rheumatoid arthritis and 1850 matched control subjects. The patients were seropositive for autoantibodies against cyclic citrullinated peptide (CCP). We obtained samples from two data sets, the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Results from NARAC and EIRA for 297,086 SNPs that passed quality-control filters were combined with the use of Cochran-Mantel-Haenszel stratified analysis. SNPs showing a significant association with disease (P<1×10-8) were genotyped in an independent set of case subjects with anti-CCP-positive rheumatoid arthritis (485 from NARAC and 512 from EIRA) and in control subjects (1282 from NARAC and 495 from EIRA). RESULTS We observed associations between disease and variants in the major-histocompatibility-complex locus, in PTPN22, and in a SNP (rs3761847) on chromosome 9 for all samples tested, the latter with an odds ratio of 1.32 (95% confidence interval, 1.23 to 1.42; P = 4×10-14). The SNP is in linkage disequilibrium with two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5). CONCLUSIONS A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis. PMID:17804836

  14. Mouse Models of Rheumatoid Arthritis.

    PubMed

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients. PMID:26063174

  15. Acral vesicles and bullae in a patient with severe rheumatoid arthritis

    PubMed Central

    Soza, Gabriela M.

    2015-01-01

    We present the case of a 56-year-old black woman with rheumatoid arthritis who developed worsening fatigue, fever, weight loss, and a vesiculobullous skin eruption while being treated with certolizumab pegol for her arthritis. Microscopic findings confirmed the diagnosis of a neutrophilic dermatosis. PMID:26424941

  16. Brief Report: Chikungunya viral arthritis in the United States: A mimic of seronegative rheumatoid arthritis

    PubMed Central

    Fox, Julie M.; Taffner, Samantha; Malkova, Olga N.; Oh, Stephen T.; Kim, Alfred H.J.; Diamond, Michael S.; Lenschow, Deborah J.; Yokoyama, Wayne M.

    2015-01-01

    OBJECTIVE Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted alphavirus that spread to the Caribbean in 2013 and the United States in 2014. CHIKV-infected patients develop inflammatory arthritis that can persist for months to years, but little is known about the rheumatologic and immunologic features of CHIKV arthritis in humans, particularly as compared to rheumatoid arthritis (RA). Here, we describe these features in a group of 10 American travelers who were nearly simultaneously infected while visiting Haiti in June 2014. METHODS Patients were assessed by history, physical examination, and laboratory studies. All patients with CHIKV arthritis had detectable anti-CHIKV IgG. Using cytometry by time of flight (CyTOF), we analyzed peripheral blood mononuclear cells in CHIKV-infected patients, healthy controls, and patients with untreated, active RA. RESULTS Among ten CHIKV-infected individuals, eight developed persistent symmetric polyarthritis, who otherwise met the 2010 ACR/EULAR criteria for (seronegative) RA. CyTOF analysis revealed that RA and CHIKV-infected patients had greater percentages of activated and effector CD4+ and CD8+ T cells than healthy controls. CONCLUSION In addition to similar clinical features, patients with CHIKV infection and RA develop highly similar peripheral T cell phenotypes. These overlapping clinical and immunologic features highlight a need for rheumatologists to consider CHIKV infection when evaluating patients with new, symmetric polyarthritis. PMID:25605621

  17. [Regaining quality of life despite rheumatoid arthritis].

    PubMed

    A, Madame

    2016-01-01

    A patient aged 32 who had been living with her partner for a few years, is diagnosed with rheumatoid arthritis. They both needed to understand and adapt. The caregivers had a frontline role in the multidisciplinary care but addressing the impact on the patient's sexual quality of life remains difficult. The patient describes her experience and how harmony and desire were re-established. PMID:27317820

  18. [Osteoporosis in Rheumatoid Arthritis: role of the vitamin D/parathyroid hormone system].

    PubMed

    Bellan, Mattia; Pirisi, Mario; Sainaghi, Pier Paolo

    2015-01-01

    Osteoporosis is a well-established extra-articular feature of Rheumatoid Arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/β catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH) system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression. PMID:25582993

  19. Vaccinations for Rheumatoid Arthritis

    PubMed Central

    Perry, Lisa M.; Winthrop, Kevin L.; Curtis, Jeffrey R.

    2014-01-01

    Patients with rheumatoid arthritis (RA) suffer an increased burden of infectious disease-related morbidity and mortality and have twice the risk of acquiring a severe infection compared to the general population. This increased risk is not only a result of the autoimmune disease but is also attributed to the immunosuppressive therapies that are commonly used in this patient population. Given the increase in infection-related risks in RA, there is great interest in mitigating such risk. A number of vaccines are available to the rheumatologist, with a handful that are of importance for RA patients in the United States. The goal of this paper is to highlight the most recent literature on the key vaccines and the specific considerations for the rheumatologist and their RA patients, with a particular focus on influenza, pneumococcal, and herpes zoster vaccines. It is important for rheumatologist to understand and be aware of which vaccines are live and what potential contraindications exist for giving vaccines to RA patients. PMID:24925587

  20. Limited T-cell receptor beta-chain heterogeneity among interleukin 2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis.

    PubMed Central

    Howell, M D; Diveley, J P; Lundeen, K A; Esty, A; Winters, S T; Carlo, D J; Brostoff, S W

    1991-01-01

    Rheumatoid arthritis (RA) is a disease affecting the synovial membranes of articulating joints that is thought to result from T-cell-mediated autoimmune phenomena. T cells responsible for the pathogenesis of RA are likely present in that fraction of synovial T cells that expresses the interleukin 2 receptor (IL-2R), one marker of T-cell activation. We report herein an analysis of T-cell receptor (TCR) beta-chain gene expression by IL-2R-positive synovial T cells. These T cells were isolated from uncultured synovial tissue specimens by using IL-2R-specific monoclonal antibodies and magnetic beads, and TCR beta-chain transcription was analyzed by PCR-catalyzed amplification using a panel of primers specific for the human TCR beta-chain variable region (V beta). Multiple V beta gene families were found to be transcribed in these patients samples; however, three gene families, V beta 3, V beta 14, and V beta 17, were found in a majority of the five synovial samples analyzed, suggesting that T cells bearing these V beta s had been selectively retained in the synovial microenvironment. In many instances, the V beta 3, V beta 14, or V beta 17 repertoires amplified from an individual patient were dominated by a single rearrangement, indicative of clonal expansion in the synovium and supportive of a role for these T cells in RA. Of note is a high sequence similarity between V beta 3, V beta 14, and V beta 17 polypeptides, particularly in the fourth complementarity-determining region (CDR). Given that binding sites for superantigens have been mapped to the CDR4s of TCR beta chains, the synovial localization of T cells bearing V beta s with significant CDR4 homology indicates that V beta-specific T-cell activation by superantigen may play a role in RA. PMID:1660155

  1. Natural killer cells and their role in rheumatoid arthritis: friend or foe?

    PubMed

    Shegarfi, Hamid; Naddafi, Fatemeh; Mirshafiey, Abbas

    2012-01-01

    Rheumatoid arthritis (RA) is a long-term disease that leads to inflammation of the joints and surrounding tissues. Natural killer (NK) cells are an important part of the innate immune system and are responsible for the first line of defense against pathogens during the initial immune challenge before the adaptive immune system eventually eliminates the infectious burden. NK cells have the capacity to damage normal cells or through interaction with other cells such as dendritic cells, macrophages, and T cells cause autoimmune diseases, such as RA. NK cells isolated from the joints of patients with RA suggest that they may play a role in this disease. However, the involvement of NK cells in RA pathology is not fully elucidated. Both protective and detrimental roles of NK cells in RA have recently been reported. A better understanding of NK cells' role in RA might help to develop new therapeutic strategies for treatment of the RA or other autoimmune diseases. We have decided in this paper to focus on the NK cell biology, and attempt to bring the interested readership of this Journal up to date on the NK cell, specifically its possible relation to RA. PMID:22547986

  2. Parasympathetic dysfunction in rheumatoid arthritis patients with ocular dryness.

    PubMed Central

    Barendregt, P J; van der Heijde, G L; Breedveld, F C; Markusse, H M

    1996-01-01

    OBJECTIVE: To determine whether abnormalities in the function of the autonomic nervous system are associated with oral and ocular dryness in rheumatoid arthritis. METHODS: Pupillography was done using an infrared light reflection method (IRIS) to measure both parasympathetic function (constriction latency and the latency of maximum constriction velocity (MCV)) and sympathetic function (dilatation latency) in rheumatoid arthritis patients with and without ocular dryness. The Schirmer and Saxon tests were used to measure the tear and saliva production respectively. RESULTS: The Schirmer and Saxon test results in rheumatoid arthritis patients with ocular dryness were reduced (P < 0.05) compared with rheumatoid arthritis patients without ocular dryness and healthy controls. Constriction latency and MCV latency were prolonged in rheumatoid arthritis patients with ocular dryness compared to the other two groups (P < 0.05). A negative correlation was found between the degree of ocular dryness and both constriction latency and MCV latency. No correlation was found between the results of pupillography and saliva production. CONCLUSIONS: Parasympathetic dysfunction may play a role in ocular dryness in patients with rheumatoid arthritis. PMID:8882130

  3. Patient-Reported Outcomes in Rheumatoid Arthritis.

    PubMed

    van Tuyl, Lilian H D; Michaud, Kaleb

    2016-05-01

    Patient-reported outcomes (PROs) and their measures have a long and important history for determining the status and treatment of patients with rheumatoid arthritis (RA). This article describes the history and evolution of PROs for RA and the current state of the field, with key examples of accepted and widely used measures, and offers some reflection on the roles of PROs for the study and management of RA. PMID:27133486

  4. Rheumatoid arthritis and pregnancy.

    PubMed

    Klipple, G L; Cecere, F A

    1989-05-01

    The activity of RA is significantly altered by pregnancy with approximately 70 per cent of patients experiencing substantial improvement in symptoms, signs and sometimes extra-articular manifestations. This lessening of disease activity occurs in association with an almost complete cessation of medications. However, whether partial or complete this remission is short-lived with more than 90 per cent of women who improved relapsing by 6 to 8 months postpartum. Further, in approximately 30 per cent of RA patients the course remains unchanged or worsens during gestation and indeed the first symptoms of RA may develop during pregnancy or shortly thereafter. Conversely active rheumatoid arthritis seems to little influence the maternal course or fetal outcome of pregnancy. The multiple and complex immunologic alterations of the pregnant state are designed to ensure survival of the fetal allograft in a foreign host. A number of these alterations particularly involving modulation of cell-mediated immunity, immunoglobulin composition, immune complex generation, or the inflammatory response have the potential to interfere with the pathophysiology of RA. In short, although the specific mechanism remains an enigma, the reason for the amelioration of RA during pregnancy is probably an incidental and fortuitous reaction to one or more of these immunomodulatory factors. PMID:2657889

  5. Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes

    PubMed Central

    Garcia-Carbonell, Ricard; Divakaruni, Ajit S.; Lodi, Alessia; Vicente-Suarez, Ildefonso; Saha, Arindam; Cheroutre, Hilde; Boss, Gerry R.; Tiziani, Stefano; Murphy, Anne N.; Guma, Monica

    2016-01-01

    Objective Up-regulation of glucose metabolism has been implicated not only in tumor cell growth but also in immune cells upon activation. However, little is known about the metabolite profile in rheumatoid arthritis (RA), particularly in fibroblast-like synoviocytes (FLS). This study was undertaken to evaluate whether changes in glucose metabolism in RA FLS could play a role in inflammation and joint damage. Methods Synovium and FLS were obtained from patients with RA and patients with osteoarthritis (OA). The rate of glycolysis after stimulation of FLS with lipopolysaccharide and platelet-derived growth factor BB was measured using glycolysis stress test technology. FLS function was evaluated using a glycolysis inhibitor, 2-deoxy-D-glucose (2-DG). After stimulation of the FLS, a migration scratch assay, MTT assay, and enzyme-linked immunosorbent assay were performed to measure the effect of 2-DG on FLS migration, viability of the FLS, and cytokine secretion, respectively. IRDye 800CW 2-DG was used to assess glucose uptake in the arthritic joints and stromal cells of mice after K/BxN mouse serum transfer. The mice were injected daily, intraperitoneally, with 3-bromopyruvate (BrPa; 5 mg/kg) to assess the effect of inhibition of glycolysis in vivo. Results Compared to human OA FLS, the balance between glycolysis and oxidative phosphorylation was shifted toward glycolysis in RA FLS. Glucose transporter 1 (GLUT1) messenger RNA (mRNA) expression correlated with baseline functions of the RA FLS. Glucose deprivation or incubation of the FLS with glycolytic inhibitors impaired cytokine secretion and decreased the rate of proliferation and migration of the cells. In a mouse model of inflammatory arthritis, GLUT1 mRNA expression in the synovial lining cells was observed, and increased levels of glucose uptake and glycolytic gene expression were detected in the stromal compartment of the arthritic mouse joints. Inhibition of glycolysis by BrPa, administered in vivo

  6. Characteristics of rheumatoid arthritis in Algeria: a multicenter study.

    PubMed

    Slimani, Samy; Abbas, Abdelmalek; Ben Ammar, Amina; Kebaili, Djemaa; Ali, El Hadi; Rahal, Fadia; Khamari, Mohamed Choukri; Baltache, Ayada; Khider, Imene; Chiheub, Riad; Khelif, Khireddine; Akbi, Sabrina; Rahmani, Salima; Dahou-Makhloufi, Chafia; Brahimi-Mazouni, Nadjia; Abtroun-Benmadi, Sabira; Ladjouze-Rezig, Aicha

    2014-09-01

    The aim of this study was to compare the epidemiology of rheumatoid arthritis (RA) in North Africa to that of Western countries. We have enrolled in a cross-sectional study all consecutive patients presenting with the diagnosis of RA according to the 1987 ACR criteria, and during a 5-month period, patients were included in 11 centers across northern Algeria. Demographics, clinical data, and health assessment questionnaires (HAQ) were collected for each patient. We have estimated means, standard deviations, and 95 % confidence intervals for all parameters. Of the 249 patients (213 females and 36 males) enrolled in the study, 10 (4 %) had juvenile onset of the disease. The mean age was 50.1 ± 14.5 years, and the mean duration of RA was 8.4 ± 7.8 years. In terms of comorbidities, 18.9 % of patients reported hypertension and 5.2 % had diabetes. The mean DAS28 at inclusion was 4.3 (95 % CI 4.1-4.5); 14.0 % were in remission (DAS28 ≤ 2.6). The mean HAQ score was 0.81 ± 0.82. Rheumatoid factor was positive in 78.5 % of cases, and anti-citrullinated protein/peptide antibodies, when measured, was positive in 69.0 % of cases. Seronegative patients were older and had a relatively less severe disease. For treatment, 89.7 % of patients were taking disease-modifying anti-rheumatic drugs and only 4 % were taking biologics (rituximab); 90.8 % of patients were taking glucocorticoids, and none of the patients satisfied the recommended calcium intake guidelines. RA in Algeria is more common in women. Compared to reports from Western countries, RA in Algeria appears to be less aggressive, with more dominant seronegative oligoarthritis forms. The remission rate is comparable to that of Western populations. PMID:24633899

  7. Immune modulation of rheumatoid arthritis.

    PubMed

    Pappas, Dimitrios A; Geraldino-Pardilla, Laura; Bathon, Joan M

    2011-12-01

    The approval - several years ago - of the first tumour necrosis factor-α (TNF-α) inhibitor for the management of rheumatoid arthritis launched a new era in the therapeutics of rheumatology. Since then an almost cataclysmic discovery of new treatment targets and corresponding biologic agents ensued. Nowadays, the rheumatologist and the rheumatologic patient have the luxury of several immune modulators available to successfully treat the majority of patients with RA or other inflammatory arthritides and conditions. In this review we focus on a discussion of the approved immune modulators/biologic agents available for the treatment of rheumatoid arthritis. We also present an overview of agents under development. For the immune modulators discussed, we describe their mechanism of action and summarise initial data and recent updates on efficacy and safety. PMID:22265267

  8. Chemokines and angiogenesis in rheumatoid arthritis

    PubMed Central

    Szekanecz, Zoltan; Pakozdi, Angela; Szentpetery, Agnes; Besenyei, Timea; Koch, Alisa E.

    2010-01-01

    In rheumatoid arthritis, chemokines mediate the migration of inflammatory leukocytes into the synovium. Among the four known chemokine families, CXC, CC chemokines and fractalkine seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important during the perpetuation of inflammation underlying rheumatoid arthritis. In this review, authors discuss the role of the most important chemokines and chemokine repetors in arthritis-associated neovascularization. The process and regulation of angiogenesis are described in this context as well. Apart from discussing the pathogenic role of chemokines and chemokine receptors in arthritic vessel formation, authors also review the important relevance of chemokines and angiogenesis for therapeutic intervention. PMID:19482623

  9. Diagnosis and management of rheumatoid arthritis.

    PubMed

    Wasserman, Amy M

    2011-12-01

    Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis. Women, smokers, and those with a family history of the disease are most often affected. Criteria for diagnosis include having at least one joint with definite swelling that is not explained by another disease. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved. In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents. Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities. Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management. PMID:22150658

  10. Rheumatoid arthritis and sexuality: A patient survey in France

    PubMed Central

    2012-01-01

    Background The objective of this study was to evaluate the impact of rheumatoid arthritis (RA) on patients’ sexuality and identify disease and other factors such as fatigue that most influence sexual relationships. Methods A specific pretested questionnaire was sent to all members of a French patient association (ANDAR). Questions related to demographics, disease status, quality of life (utility, EQ-5D), pain, psychological status (mood), fatigue and emotional and sexual relationships. To isolate the impact of RA, an attempt was made to include a matched sample from the general population. Results The analysis included 1271 patients, but only 70 controls agreed to participate and comparisons should therefore be considered with caution. The two groups were similar in terms of age, gender distribution, living conditions and diseases other than RA. However, patients scored worse for global health, mood, fatigue, had a lower utility (0.55 versus 0.65). Controls were more active sexually (69% versus 63%), in particular women (71% versus 60%). Age, gender, living alone, physical function and mood were significant predictors for being sexually active for patients; for controls, age and overall quality of life (utility) were significant predictors. Conclusions While it is known that RA has a negative impact on patients’ sexuality, there have been few attempts to quantify the problem. Our study highlights the negative impact of RA on patients’ sexuality, and triggers the question how to include this aspect into care. PMID:22963081

  11. Autoimmune Thyroid Disease in Rheumatoid Arthritis: A Global Perspective

    PubMed Central

    Cárdenas Roldán, Jorge; Amaya-Amaya, Jenny; Castellanos-de la Hoz, Juan; Giraldo-Villamil, Juliana; Montoya-Ortiz, Gladys; Cruz-Tapias, Paola; Rojas-Villarraga, Adriana; Mantilla, Rubén D.; Anaya, Juan-Manuel

    2012-01-01

    Objective. To determine the prevalence and impact of autoimmune thyroid disease (AITD) in patients with rheumatoid arthritis (RA). Methods. Eight-hundred patients were included. The association between AITD and RA was analyzed was analyzed by bivariate and multivariate analysis. In addition, a literature review was done focusing on geographical variations. Results. In our cohort the prevalence of AITD was 9.8% while the presence of antibodies was 37.8% for antithyroperoxidase enzyme (TPOAb) and 20.8% for antithyroglobulin protein (TgAb). The presence of type 2 diabetes, thrombosis, abnormal body mass index, and a high educational level was positively associated with AITD. The literature review disclosed a geographical variation of AITD in RA ranging from 0.5% to 27%. Autoantibody prevalence ranges from 6% to 31% for TgAb, 5% to 37% for TPOAb, and from 11.4% to 32% for the presence of either of the two. Conclusion. AITD is not uncommon in RA and should be systematically assessed since it is a risk factor for developing diabetes and cardiovascular disease. These results may help to further study the common mechanisms of autoimmune diseases, to improve patients' outcome, and to define public health policies. An international consensus to accurately diagnose AITD is warranted. PMID:23209899

  12. [A case of rheumatoid arthritis involving disseminated torichosporonosis].

    PubMed

    Ueda, Yo; Yamashita, Hiroyuki; Yoshida, Yuji; Takahashi, Yuko; Mimori, Akio

    2011-09-01

    A 75-year-old man who developed disseminated trichosporonosis had a long history of immunosuppressive therapy with weekly methotrexate and low-dose prednisolone for rheumatoid arthritis (RA). He had been administered 30 mg of prednisolone per day for organizing pneumonia, probably due to the RA, for about 3 months before admission for a lumbar compression fracture. He then developed bilateral aspiration pneumonia with pleural effusion, treated successfully with broad-spectrum antibiotics meropenem and ciprofloxacin, and fluid management. He then developed acute, progressive respiratory failure with changes in both lung lobes in chest computed tomography (CT). Meropenem, ciprofloxacin, micafungin, and pulsed steroid administration were ineffective. He died of respiratory failure, after which Trichosporon asahii was first detected in blood and urine culture. Disseminated trichosporonosis was determined based on positive blood culture, elevated serum glucuronoxylomannan antigen and beta-D glucan, and the man's lack of clinical progress. He had numerous risk factors for trichosporonosis, including neutrophilic dysfunction due to prolonged steroid therapy, administration of broad-spectrum antibiotics and micafungin, and central venous catheterization. Disseminated trichosporonosis is a chiefly hematological infection and case reports without hematological disorders are rare, so we report this instructive case. PMID:22117385

  13. Current therapies in rheumatoid arthritis: a Latin American perspective.

    PubMed

    Burgos-Vargas, Rubén; Catoggio, Luis Jose; Galarza-Maldonado, Claudio; Ostojich, Kasmir; Cardiel, Mario H

    2013-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting the synovium of joints, tendons, and some extra-articular sites. RA prevalence in Latin America ranges from 0.4 to 1.6%. Early treatment of RA translates into a substantial reduction in the cost to society. In light of this, early disease clinics are being established in some countries. Barriers to RA management, such as delay in referral to rheumatologists and limited access to therapy, have been identified. Evidence-based treatment guidelines have been adapted by countries according to their own situations. The need for keeping accurate records of biologics prescribed has been addressed by biologic registries, thereby contributing toward a better understanding of rheumatic diseases and their treatment. Current biologics include the tumor necrosis factor (TNF)-α inhibitors (etanercept, infliximab, and adalimumab), B-cell depletion agent (rituximab), interleukin-6 receptor blocker (tocilizumab), and T-cell co-stimulatory blocker (abatacept). Future therapies include kinase inhibitors (tofacitinib and fostamatinib), alternative TNF-α inhibitors (golimumab and certolizumab), and biosimilars. PMID:23337169

  14. Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review.

    PubMed

    Nevius, Erin; Gomes, Ana Cordeiro; Pereira, João P

    2016-08-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Self-reactive B and T lymphocytes cooperate to promote antibody responses against self proteins and are major drivers of disease. T lymphocytes also promote RA independently of B lymphocytes mainly through the production of key inflammatory cytokines, such as IL-17, that promote pathology. While the innate signals that initiate self-reactive adaptive immune responses are poorly understood, the disease is predominantly caused by inflammatory cellular infiltration and accumulation in articular tissues, and by bone erosions driven by bone-resorbing osteoclasts. Osteoclasts are giant multinucleated cells formed by the fusion of multiple myeloid cells that require short-range signals, such as the cytokines MCSF and RANKL, for undergoing differentiation. The recruitment and positioning of osteoclast precursors to sites of osteoclast differentiation by chemoattractants is an important point of control for osteoclastogenesis and bone resorption. Recently, the GPCR EBI2 and its oxysterol ligand 7a, 25 dihydroxycholesterol, were identified as important regulators of osteoclast precursor positioning in proximity to bone surfaces and of osteoclast differentiation under homeostasis. In chronic inflammatory diseases like RA, osteoclast differentiation is also driven by inflammatory cytokines such as TNFa and IL-1, and can occur independently of RANKL. Finally, there is growing evidence that the chemotactic signals guiding osteoclast precursors to inflamed articular sites contribute to disease and are of great interest. Furthering our understanding of the complex osteoimmune cell interactions should provide new avenues of therapeutic intervention for RA. PMID:26511861

  15. Sexual dysfunction in rheumatoid arthritis: a hot but sensitive issue.

    PubMed

    Palmer, Deborah; El Miedany, Yasser

    Rheumatoid arthritis (RA) has considerable personal impact for sufferers and their families. Those with RA suffer from pain, restricted joint movements, and fatigue, and can have problems with self-esteem and body image. It is also possible that medication causes sexual problems. Research on the subject is limited, and shows a divergent picture. Assessment for sexual dysfunction in clinical practice might be another hurdle, as patients and health professionals are reluctant to discuss this issue face to face. The aim of the work carried out and described in this article was to study the possibility of implementing sexual dysfunction assessment into standard rheumatology clinical practice. Results revealed that the multidimensional patient-reported outcome measures questionnaire offered the opportunity to assess the disease activity parameters, functional disability, quality of life, sexual dysfunction, and self-helplessness in one format. The patients appeared willing to complete questionnaires and this may be an acceptable tool for assessment. Improving patient education, as well as nurse-patient communication, through discussions about available options may minimize patients' feelings of isolation in addressing the problem and could help compensate for negative effects resulting from the disease. PMID:22067584

  16. Role of reactive oxygen and nitrogen species in etiopathogenesis of rheumatoid arthritis.

    PubMed

    Bauerová, K; Bezek, A

    1999-10-01

    Rheumatoid arthritis (RA) is a chronic disease affecting up to 3% of the population in most countries. The causes of RA have not been completely elucidated. This paper aims to review the role of reactive oxygen and nitrogen species in the etiopathogenesis of RA. Reactive oxygen species (ROS), such as superoxide radical, hydrogen peroxide, hydroxyl radical and hypochlorous acid, as well as reactive nitrogen species (RNS), such as nitric oxide and peroxynitrite, contribute significantly to tissue injury in RA. Several mechanisms are involved in the generation and action of ROS and RNS. Superoxide radical, hydrogen peroxide and nitric oxide do not directly damage the majority of biological molecules. They are however converted into the highly reactive hydroxyl radical, which reacts with almost all molecules in living cells. The resulting chronic inflammation process can be reduced with antioxidant therapy. To date, scavenging, preventive, and enzyme antioxidants are available. The most important mode is scavenging of the hydroxyl radical and of hypochlorous acid. Another important way is to inhibit production of RNS and ROS by neutrophils, monocytes, and macrophages. The control of inflammation in arthritic patients by natural as well as synthetic antioxidants could become a relevant component of antirheumatic prevention and therapy. PMID:10703714

  17. 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. PMID:26555550

  18. A Case of REM Sleep Behavior Disorder, Narcolepsy-Cataplexy, Parkinsonism, and Rheumatoid Arthritis

    PubMed Central

    Cosentino, Filomena I. I.; Distefano, Angela; Plazzi, Giuseppe; Schenck, Carlos H.

    2014-01-01

    A patient is reported in whom signs and symptoms of REM sleep behavior disorder (RBD) and narcolepsy have been associated for almost two decades with a late development of parkinsonism and rheumatoid arthritis. A 78-year-old male patient in whom RBD was first diagnosed was followed-up by clinical examination, video-polysomnography, multiple sleep latency test, cerebral magnetic resonance imaging, and dopamine transporter imaging by single-photon emission computerized tomography. The patient was found to present for almost two decades, in addition to RBD, also narcolepsy. Moreover, a late development of parkinsonism and the occurrence of rheumatoid arthritis were detected and clinically and instrumentally characterized. Patients predisposed to RBD and later parkinsonism might be susceptible to a variety of triggers that, in our patient, might have been represented by a possible latent autoimmune process leading to the development of narcolepsy with cataplexy and rheumatoid arthritis, later. PMID:24825961

  19. Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial

    PubMed Central

    van Jaarsveld, C H M; Jacobs, J; van der Veen, M J; Blaauw, A; Kruize, A; Hofman, D; Brus, H; van Albada-Kuiper..., G A; Heurkens, A; ter Borg, E J; Haanen, H; van Booma-Frankfo..., C; Schenk, Y; Bijlsma, J

    2000-01-01

    OBJECTIVES—To compare three therapeutic strategies using slow acting antirheumatic drugs (SAARDs) in early rheumatoid arthritis (RA), for their disease modifying properties, toxicity, and lag time until treatment effect.
METHODS—Patients with recent onset RA from six hospitals were randomly assigned to immediate initiation of one of three treatment strategies: (I) a "mild SAARD with a long lag time" (hydroxychloroquine, if necessary replaced by auranofin); (II) a "potent SAARD with a long lag time" (intramuscular gold, if necessary replaced by D-penicillamine); (III) a "potent SAARD with a short lag time" (methotrexate, if necessary replaced by sulfasalazine). Comparisons included two years of follow up.
RESULTS—All SAARD strategies reduced mean disease activity. A greater percentage of patients improved clinically with strategies II and III than with strategy I: percentages of patients improved on joint score with strategies II and III (79% and 82%, respectively), which was statistically different from strategy I (66%). The same was true for remission percentages: 31% and 24% v 16%, respectively). Longitudinal analysis showed significantly less disability with strategy III, and a lower erythrocyte sedimentation rate with strategy II than with strategy I. In addition, radiological damage after one and two years, was significantly lower in strategies II and III (at two years median scores were 11 and 10 v 14 in strategy I, p<0.05). Toxicity was increased in strategy II compared with the other strategies.
CONCLUSION—Strategy III, comprising methotrexate or sulfasalazine, produced the best results weighing effectiveness and toxicity. Strategy I (hydroxychloroquine or auranofin) was slightly less effective, and strategy II (intramuscular gold or D-penicillamine) was associated with increased toxicity.

 PMID:10834865

  20. New onset psoriasis in a patient receiving abatacept for rheumatoid arthritis

    PubMed Central

    Jost, Christina; Hermann, Josef; Caelen, Laila El-Shabrawi; Graninger, Winfried

    2009-01-01

    Administration of abatacept is a new treatment modality for rheumatoid arthritis (RA). We describe a patient in whom psoriasiform skin lesions developed 4 months after the initiation of abatacept therapy for longstanding, rheumatoid factor positive RA. Histological findings were consistent with psoriasis. The skin lesions subsided after discontinuation of abatacept and reappeared after re-exposure to the drug, suggesting a causal connection between abatacept and the development of psoriasis. PMID:21686603

  1. 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

  2. The occurrence of a geode in the olecranon of a patient with rheumatoid arthritis.

    PubMed

    Torikai, Eiji; Kageyama, Yasunori; Sugiyama, Eiji; Ogiwara, Yoshihiro; Irisawa, Satoshi; Nagano, Akira

    2006-03-01

    Geode, a subchondral cyst, is sometimes seen in the femur, knee, or wrist in a patient with rheumatoid arthritis (RA). But the onset of a giant geode at the olecranon is extremely rare in a patient with RA. We describe herein a rare case of a giant geode at the olecranon in a patient with RA. PMID:16402200

  3. The Role of Citrullinated Protein Antibodies in Predicting Erosive Disease in Rheumatoid Arthritis: A Systematic Literature Review and Meta-Analysis

    PubMed Central

    Jilani, A. A.; Mackworth-Young, C. G.

    2015-01-01

    Background. Autoantibodies to citrullinated peptides have been shown to be valuable in the diagnosis of rheumatoid arthritis (RA). The expanding repertoire of antibodies to citrullinated peptide antigens (ACPA) has been a topic of great interest in recent reviews and research studies, as has the ability of these autoantibodies to predict disease outcome. Objectives. The aim of this review was to provide an update on the relevance of ACPA as prognostic markers in RA. The ability to identify patients predisposed to an aggressive outcome at the time of initial diagnosis greatly facilitates the selection of appropriate and cost-effective treatment. Methods. A systematic review of the literature was carried out. Studies from 1967 up to June 2014 with data on prognostic value of ACPA were included. Quality assessment was done by using the modified Hayden list for prognostic studies. Meta-analysis was performed using BioStat software. Results. The results of 25 studies were selected for the final review. A total of 6421 patients with RA were included, mainly in inception cohorts, with follow-up duration ranging from one year to ten years. All studies carried prognostic data on all available isotypes of anticyclic citrullinated protein (CCP), while four had data on antimutated citrullinated vimentin (MCV). There was a single relevant study each on anticitrullinated enolase peptide 1 (CEP1) and antichimaeric fibrin/filaggrin citrullinated peptide 1 (CFFCP1). All studies showed ACPA to be strong predictors of joint erosions in RA. Other factors, particularly baseline erosions, showed an additive effect. Anti-MCV appeared to be a marker of a more aggressive form of disease. Ten studies had data on which a meta-analysis could be performed. This gave an overall odds ratio of 4.85 for ACPA (anti-CCP/MCV) positivity being predictive for the development of joint erosions. Two studies with data on anti-CEP1 and anti-CFFCP1 also showed this positive predictive role of ACPA for joint

  4. Ulcerative colitis and rheumatoid arthritis: a rare association--case report.

    PubMed

    Cruz, Vitor Alves; Yamaguchi, Lúcio; Ribeiro, Carolina Nazeozeno; Magalhães, Vanessa de Oliveira; Rego, Jozelia; Silva, Nilzio Antonio da

    2012-08-01

    Ulcerative colitis is an autoimmune disorder of unknown etiology. Although the large intestine is the major focus of autoimmunity, resulting in chronic diarrhea, that is actually a systemic disease, with numerous extraintestinal manifestations, such as articular involvement. The frequent association of a number of autoimmune diseases in the same patient has been described. However, the coexistence of ulcerative colitis and rheumatoid arthritis is rare. The authors report a case of ulcerative colitis associated with rheumatoid arthritis, in which colitis occurred 12 years before the onset of inflammatory arthropathy. PMID:22885429

  5. Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin.

    PubMed Central

    Hoet, R M; Boerbooms, A M; Arends, M; Ruiter, D J; van Venrooij, W J

    1991-01-01

    The antiperinuclear factor, an autoantibody specific for rheumatoid arthritis, was found in 51/63 (81%) patients with rheumatoid arthritis by indirect immunofluorescence on human buccal mucosa cells. The sensitivity of the antiperinuclear factor test was increased by pretreating the buccal mucosa cells with 0.5% Triton-X100. The specificity of the test for rheumatoid arthritis as compared with control serum samples was maintained. The localisation of the perinuclear factor in the keratohyalin granules of the buccal mucosa cells was verified by immunoelectron microscopy. The perinuclear factor was found to be an insoluble protein whose antigenicity was sensitive to various fixation procedures. In serum samples from patients with rheumatoid arthritis there was a positive correlation between the presence of antiperinuclear factor and the presence of the so called antikeratin antibodies as detected by immunofluorescence on unfixed rat oesophagus cryostat sections. No relation was found between the presence of the perinuclear factor and either the rheumatoid factor, Epstein-Barr virus components, or any cytokeratin. By double immunofluorescence an exact colocalisation of the perinuclear factor and profilaggrin was found. Although the precise biochemical identity of the perinuclear factor remains unclear, our results suggest that it is a protein only present in the fully differentiated squamous epithelial cell layer. Images PMID:1718228

  6. Fluorescence imaging of experimental rheumatoid arthritis in vivo using a fast flying-spot scanner

    NASA Astrophysics Data System (ADS)

    Berger, J.; Voigt, J.; Seifert, F.; Ebert, B.; Macdonald, R.; Gemeinhardt, I.; Gemeinhardt, O.; Schnorr, J.; Taupitz, M.; Vater, A.; Vollmer, S.; Licha, K.; Schirner, M.

    2007-07-01

    We have developed a flying-spot scanner for fluorescence imaging of rheumatoid arthritis in the near infrared (NIR) spectral range following intravenous administration of contrast agents. The new imaging system has been characterized with respect to linearity, dynamic range and spatial resolution with the help of fluorescent phantoms. In vivo experiments were performed on an animal model of rheumatoid arthritis. Finally, NIR-fluorescence images of early stages of joint inflammation have been compared with findings from contrast enhanced MR imaging and histology.

  7. Changes of lymphocyte membrane fluidity in rheumatoid arthritis: a fluorescence polarisation study.

    PubMed Central

    Beccerica, E; Piergiacomi, G; Curatola, G; Ferretti, G

    1988-01-01

    Fluorescence polarisation of 1,6-diphenyl-1,3,5-hexatriene was used to study the lymphocyte membrane in rheumatoid arthritis. The increase of polarisation value in the patients (n = 27) compared with healthy controls (n = 32) suggests a decrease of membrane fluidity. Moreover, erythrocyte sedimentation rate (ESR) and plasma fibrinogen concentrations were positively correlated with lymphocyte fluorescence polarisation values (r = 0.66 and r = 0.76 respectively). The results suggest that the changes in lymphocyte membrane fluidity could be involved in the pathogenetic mechanism of rheumatoid arthritis. PMID:3382266

  8. The role of free radicals in the pathogenesis of rheumatoid arthritis.

    PubMed

    Hadjigogos, K

    2003-03-01

    Free radicals are reactive chemical species that differ from other compounds in that they have unpaired electrons in their outer orbitals. They are capable of damaging cellular components, and accumulating evidence suggests that they may contribute to various disease entities including inflammatory joint disease. Reactive oxygen species (ROS) as well as reactive nitrogen species (RNS) can directly or indirectly damage basic articular constituents and lead to the clinical expression of the inflammatory arthritis. Hydroxyl radicals degrade isolated proteoglycans, and HOCl fragments collagen. Hydrogen peroxide, which is very diffusible, readily inhibits cartilage proteoglycan synthesis, e.g. by interfering with ATP synthesis, in part by inhibiting the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase in chondrocytes, aggravating the effects of proteolytic and free-radical-mediated cartilage degradation. Peroxynitrite and HOCl may facilitate cartilage damages by inactivating TIMPs. TIMP-1 inhibits stromelysins, collagenases and gelatinases and this ability is lost after ONOO(-) or HOCl treatment. HOCl can also activate latent forms of neutrophil collagenases and gelatinase with obvious consequences. Hypochlorous acid, ONOO(-) and O(2)(*-) react with ascorbate, which is essential for cartilage function, leading to low levels of ascorbate in synovial fluid. Low concentrations of H2O(2), O(2)(*-) or both, accelerate bone resorption by osteoclasts, whereas NO. inhibits it. NO. promotes chondrocyte apoptosis, inhibits proteoglycan synthesis and activates latent metalloproteinases and cyclooxygenase. ROS, produced by activated phagocytes, could alter the antigenic behaviour of immunoglobulin G, producing fluorescent protein aggregates that can further activate phagocytic cells. Radical-exposed IgG is able to bind rheumatoid factor and results in the generation of C3alpha. This reaction may be self-perpetuating within the rheumatoid joint, suggesting that free

  9. 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 ...

  10. Interleukin 6 and rheumatoid arthritis.

    PubMed

    Yoshida, Yuji; Tanaka, Toshio

    2014-01-01

    Interleukin-6 (IL-6) is a representative cytokine featuring pleiotropic activity and redundancy. A transient synthesis of IL-6 contributes to host defense against infectious agents and tissue injuries by inducing acute phase reactions and immunological and hematopoietic responses. However, uncontrolled persistent production of IL-6 may lead to the development of several immune-mediated diseases. Rheumatoid arthritis (RA) is a chronic disease with joint and systemic inflammation resulting from immunological abnormalities and it has been found that IL-6 plays a key role in the development of this disease. Clinical trials in various parts of the world of tocilizumab, a humanized anti-IL-6 receptor antibody, have proved its efficacy and tolerable safety either as monotherapy or in combination with disease-modifying antirheumatic drugs. As a result, it is currently used as a first-line biologic for the treatment of moderate-to-severe RA in more than 100 countries. Clarification of the mechanism(s) through which tocilizumab exerts its effect on RA and of the reason(s) why IL-6 is continuously produced in RA can be expected to lead to the best use of this agent for RA patients and aid in investigations into the pathogenesis of RA. PMID:24524085

  11. No rheumatoid arthritis in ancient Egypt: a reappraisal.

    PubMed

    Kwiecinski, Jakub; Rothschild, Bruce M

    2016-06-01

    Antiquity of rheumatoid arthritis (RA) remains controversial, and its origins in Americas or in the Old World are disputed. Proponents of the latter frequently refer to RA in ancient Egypt, but validity of those claims has never been examined. Review of all reported RA cases from ancient Egypt revealed that none of them represent real RA, instead being either examples of changing naming conventions or of imprecise diagnostic criteria. Most cases represented osteoarthritis or spondyloarthropathies. Also review of preserved ancient Egyptian medical writings revealed many descriptions of musculoskeletal disorders, but none of them resembled RA. This suggests that RA was absent in ancient Egypt and supports the hypothesis of the New World origin of RA and its subsequent global spread in the last several centuries. PMID:26650735

  12. The supplementary therapeutic DMARD role of low-dose glucocorticoids in rheumatoid arthritis

    PubMed Central

    2014-01-01

    The management of rheumatoid arthritis (RA) is primarily based on the use of disease-modifying antirheumatic drugs (DMARDs), mainly comprising synthetic chemical compounds (that is, methotrexate or leflunomide) and biological agents (tumor necrosis factor inhibitors or abatacept). On the other hand, glucocorticoids (GCs), used for decades in the treatment of RA, are effective in relieving signs and symptoms of the disease, but also interfere with radiographic progression, either as monotherapy or in combination with conventional synthetic DMARDs. GCs exert most of their biological effects through a genomic action, using the cytosolic GC receptor and then interacting with the target genes within target cells that can result in increased expression of regulatory - including anti-inflammatory - proteins (transactivation) or decreased production of proinflammatory proteins (transrepression). An inadequate secretion of GCs from the adrenal gland, in relation to stress and inflammation, seems to play an important role in the pathogenesis and disease progression of RA. At present there is clear evidence that GC therapy, especially long-term low-dose treatment, slows radiographic progression by at least 50% when given to patients with early RA, hence satisfying the conventional definition of a DMARD. In addition, long-term follow-up studies suggest that RA treatment strategies which include GC therapy may favorably alter the disease course even after their discontinuation. Finally, a low-dose, modified night-release formulation of prednisone, although administered in the evening (replacement therapy), has been developed to counteract the circadian (night) rise in proinflammatory cytokine levels that contributes to disease activity, and might represent the way to further optimize the DMARD activity exerted by GCs in RA. PMID:25608624

  13. The microbiome and rheumatoid arthritis

    PubMed Central

    Scher, Jose U.; Abramson, Steven B.

    2012-01-01

    Humans are not (and have never been) alone. From the moment we are born, millions of micro-organisms populate our bodies and coexist with us rather peacefully for the rest of our lives. This microbiome represents the totality of micro-organisms (and their genomes) that we necessarily acquire from the environment. Micro-organisms living in or on us have evolved to extract the energy they require to survive, and in exchange they support the physiological, metabolic and immune capacities that have contributed to our evolutionary success. Although currently categorized as an autoimmune disorder and regarded as a complex genetic disease, the ultimate cause of rheumatoid arthritis (RA) remains elusive. It seems that interplay between predisposing genetic factors and environmental triggers is required for disease manifestation. New insights from DNA sequence-based analyses of gut microbial communities and a renewed interest in mucosal immunology suggest that the microbiome represents an important environmental factor that can influence autoimmune disease manifestation. This Review summarizes the historical clues that suggest a possible role for the microbiota in the pathogenesis of RA, and will focus on new technologies that might provide scientific evidence to support this hypothesis. PMID:21862983

  14. Oxidative Stress Relevance in the Pathogenesis of the Rheumatoid Arthritis: A Systematic Review

    PubMed Central

    Quiñonez-Flores, Celia María; González-Chávez, Susana Aideé; Del Río Nájera, Danyella; Pacheco-Tena, César

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease whose pathogenic mechanisms remain to be elucidated. The oxidative stress and antioxidants play an important role in the disease process of RA. The study of oxidants and antioxidants biomarkers in RA patients could improve our understanding of disease pathogenesis; likely determining the oxidative stress levels in these patients could prove helpful in assessing disease activity and might also have prognostic implications. To date, the usefulness of oxidative stress biomarkers in RA patients is unclear and the evidence supporting them is heterogeneous. In order to resume and update the information in the status of oxidants and antioxidants and their connection as biomarkers in RA, we performed a systematic literature search in the PubMed database, including clinical trials published in the last five years using the word combination “rheumatoid arthritis oxidative stress”. In conclusion, this review supports the fact that the oxidative stress is an active process in RA pathogenesis interrelated to other better known pathogenic elements. However, some controversial results preclude a definite conclusion. PMID:27340664

  15. Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts

    PubMed Central

    Müller-Ladner, Ulf; Ospelt, Caroline; Gay, Steffen; Distler, Oliver; Pap, Thomas

    2007-01-01

    For some time synovial fibroblasts have been regarded simply as innocent synovial cells, mainly responsible for synovial homeostasis. During the past decade, however, a body of evidence has accumulated illustrating that rheumatoid arthritis synovial fibroblasts (RASFs) are active drivers of joint destruction in rheumatoid arthritis. Details regarding the intracellular signalling cascades that result in long-term activation and synthesis of proinflammatory molecules and matrix-degrading enzymes by RASFs have been analyzed. Molecular, cellular and animal studies have identified various interactions with other synovial and inflammatory cells. This expanded knowledge of the distinct role played by RASFs in the pathophysiology of rheumatoid arthritis has moved these fascinating cells to the fore, and work to identify targeted therapies to inhibit their joint destructive potential is underway. PMID:18177509

  16. A Crossover Trial Evaluating an Educational-Behavioral Joint Protection Programme for People with Rheumatoid Arthritis.

    ERIC Educational Resources Information Center

    Hammond, A.; Lincoln, N.; Sutcliffe, L.

    1999-01-01

    Joint protection, a self-management technique taught to people with rheumatoid arthritis, was used in a group education program. A crossover trial (N=35) was conducted. No significant changes in measures of pain, functional disability, grip strength, self-efficacy or helplessness occurred post-education, although this may have been due to the…

  17. [Vasculitis in rheumatoid arthritis].

    PubMed

    Bély, M; Apáthy, A

    1996-07-21

    The frequency and histopathological characteristics of systemic vasculitis were studied in the autopsy material of 161 patients with rheumatoid arthritis. Systemic vasculitis was observed in 36 case (22.4%). In percentage of all cases with systemic vasculitis, the most frequently involved organs were the heart (66.7%), skeletal muscles (54.8%), and peripheral nerves (52%). The skin was involved only in about one third of 36 cases (36%). In most cases the arterioles and the small arteries were affected by vasculitis. Three types of vasculitis (non specific, fibrinoid necrotic, granulomatous) could be observed simultaneously in different vessels or combined in the same vessel. Different stages of inflammation could be found simultaneously, reflecting the relapsing nature of vasculitis. The frequency, the severity, and the recurrence of vasculitis are different aspects of the same phenomenon running usually parallel to each other in different organs and on different vessels. Vasculitis lead to local ischaemia and regressive changes depend on the number and size of the involved vessels. Systemic vasculitis led to death in 19 of 36 cases. Vasculitis was detected clinically in 7 of 36 cases. Exitus lethalis depend on the localization of the involved vessels. Vasculitis in the heart and brain are more life threatening, than that of localized to the skin. PMID:8757068

  18. Overexpression of P-glycoprotein on fibroblast-like synoviocytes in refractory rheumatoid arthritis patients: a potential mechanism for multidrug resistance in rheumatoid arthritis treatment.

    PubMed

    Liu, Y M; Chen, J W; Chen, L X; Xie, X; Mao, N

    2016-01-01

    This study aims to investigate the role of P-glycoprotein (P-gp) expression level in drug resistance to disease-modifying anti-rheumatic drugs in refractory rheumatoid arthritis (RRA). We evaluated and compared the expression levels of P-gp in fibroblast-like synoviocyte (FLS) cells in patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and investigated the potential mechanism of P-gp-induced multidrug resistance in RRA. Ten patients were enrolled and divided into two groups: six in the RA group and four in the OA group. The expression level of P-gp in FLS cells was detected by western blotting following cell culture. A linear correlation algorithm was used to assess the association between the level of P-gp and disease activity  (using DAS28 scoring), as well as the duration of methotrexate (MTX) treatment in the RRA patients. The level of P-gp in the RRA patients was markedly higher than that in the OA patients (P < 0.05, t = -4.179). There was a positive linear correlation between the P-gp level in FLS cells and the duration of MTX treatment in the RRA group (Г = 0.733, P < 0.05), whereas there was no significant correlation between the P-gp level and DAS28 scoring (Г = 0.206, P > 0.05). P-gp might be upregulated during the progression of RRA, which possibly correlates with the development of resistance to MTX. PMID:27323187

  19. Patient Preferences Regarding Rheumatoid Arthritis Therapies: A Conjoint Analysis

    PubMed Central

    Louder, Anthony M.; Singh, Amitabh; Saverno, Kim; Cappelleri, Joseph C.; Aten, Aaron J.; Koenig, Andrew S.; Pasquale, Margaret K.

    2016-01-01

    Background Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments. Objective To investigate patient preferences for attributes associated with RA treatments. Methods A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21–80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had ≥2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to perform daily tasks; and medication burden. Mean attribute importance scores were calculated after adjusting for patient demographics (eg, age, sex, years since diagnosis) using a hierarchical Bayes model. Patient preferences for each treatment attribute were ranked by the importance score. Part-worth utilities (ie, preference scores) were used to perform a conjoint market simulation. Results A total of 380 patients (response rate, 27.1%) returned the survey. Their mean age (± standard deviation) was 54.9 (± 9.3) years. Nonrespondents were 2 years younger (mean, 52.9 years; P = .002) but did not differ significantly from respondents in known clinical characteristics. After adjustment for demographic characteristics, mean patients' ranking of treatment attribute importance, in decreasing order, was route of administration, 34.1 (± 15.5); frequency of administration, 16.4 (± 6.8); serious adverse events, 12.0 (± 9.3); cost, 10.1 (± 6.2); medication

  20. The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview.

    PubMed

    Clapp, Carmen; Adán, Norma; Ledesma-Colunga, María G; Solís-Gutiérrez, Mariana; Triebel, Jakob; Martínez de la Escalera, Gonzalo

    2016-08-01

    Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits. PMID:27026299

  1. 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

  2. Do You Have a Child with Juvenile Rheumatoid Arthritis in Your Class?

    ERIC Educational Resources Information Center

    Ferris, Jean; Fujishige, Carole

    The booklet provides information to help teachers understand juvenile rheumatoid arthritis (JRA). JRA is a chronic disease involving one or more joint(s); its cause is unknown. The five types of JRA are monarticular, pauciarticular of young girls, pauciarticular of boys, polyarticular, and systemic. Aspirin is the main treatment medication and…

  3. Therapeutic implications of autoantibodies in rheumatoid arthritis

    PubMed Central

    Aletaha, Daniel; Blüml, Stephan

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by the presence of autoantibodies. Their value for diagnostic/prognostic purposes has been well established. In contrast, their role in established disease and their associations with disease activity is less clear. Moreover, as evidence is accumulating that these autoantibodies are causally involved in certain key aspects of the disease, such as the initiation and perpetuation of joint inflammation or join destruction, autoantibodies in RA can no longer be regarded as mere epiphenomena, but are integral elements of the pathophysiology of RA. PMID:27252890

  4. Comparative Persistence of the TNF Antagonists in Rheumatoid ArthritisA Population-Based Cohort Study

    PubMed Central

    Fisher, Anat; Bassett, Ken; Wright, James M.; Brookhart, M. Alan; Freeman, Hugh; Dormuth, Colin R.

    2014-01-01

    Objective To compare persistence with tumor necrosis factor alpha (TNF) antagonists among rheumatoid arthritis patients in British Columbia. Treatment persistence has been suggested as a proxy for real-world therapeutic benefit and harm of treatments for chronic non-curable diseases, including rheumatoid arthritis. We hypothesized that the different pharmacological characteristics of infliximab, adalimumab and etanercept cause statistically and clinically significant differences in persistence. Methods We conducted a population-based cohort study using administrative health data from the Canadian province of British Columbia. The study cohort included rheumatoid arthritis patients who initiated the first course of a TNF antagonist between 2001 and 2008. Persistence was measured as the time between first dispensing to discontinuation. Drug discontinuation was defined as a drug-free interval of 180 days or switching to another TNF antagonist, anakinra, rituximab or abatacept. Persistence was estimated and compared using survival analysis. Results The study cohort included 2,923 patients, 63% treated with etanercept. Median persistence in years (95% confidence interval) with infliximab was 3.7 (2.9–4.9), with adalimumab 3.3 (2.6–4.1) and with etanercept 3.8 (3.3–4.3). Similar risk of discontinuation was observed for the three drugs: the hazard ratio (95% confidence interval) was 0.98 (0.85–1.13) comparing infliximab with etanercept, 0.95 (0.78–1.15) comparing infliximab with adalimumab and 1.04 (0.88–1.22) comparing adalimumab with etanercept. Conclusions Similar persistence was observed with infliximab, adalimumab and etanercept in rheumatoid arthritis patients during the first 9 years of use. If treatment persistence is a good proxy for the therapeutic benefit and harm of these drugs, then this finding suggests that the three drugs share an overall similar benefit-harm profile in rheumatoid arthritis patients. PMID:25141123

  5. Autonomic Dysfunction Precedes Development of Rheumatoid Arthritis: A Prospective Cohort Study

    PubMed Central

    Koopman, F.A.; Tang, M.W.; Vermeij, J.; de Hair, M.J.; Choi, I.Y.; Vervoordeldonk, M.J.; Gerlag, D.M.; Karemaker, J.M.; Tak, P.P.

    2016-01-01

    Background Heart rate variability (HRV) is a validated method to establish autonomic nervous system (ANS) activity. Rheumatoid arthritis (RA) is accompanied by ANS imbalance. We hypothesized that ANS dysfunction may precede the development of RA, which would suggest that it plays a role in its etiopathogenesis. Methods First, we assessed HRV parameters in supine (resting) and upright (active) position in healthy subjects (HS, n = 20), individuals at risk of developing arthritis (AR subjects, n = 50) and RA patients (RA, n = 20). Next, we measured resting heart rate (RHR), a parasympathetic HRV parameter, in an independent prospective cohort of AR subjects (n = 45). We also evaluated expression levels of the parasympathetic nicotinic acetylcholine receptor type 7 (α7nAChR) on circulating monocytes. Findings Both AR subjects (68 beats per minute (bpm), interquartile range (IQR) 68–73) and RA patients (68 bpm, IQR 62–76) had a significantly higher RHR compared to HS (60 bpm, IQR 56–63). RHR was significantly higher at baseline in individuals who subsequently developed arthritis. Expression levels of α7nAChR were lower in AR subjects with RHR ≥ 70 bpm compared to those with RHR < 70 bpm, consistent with reduced activity of the parasympathetic cholinergic anti-inflammatory pathway. Interpretation These data support the notion that autonomic dysfunction precedes the development of RA. PMID:27211565

  6. A study on FoxP3 and Tregs in paired samples of peripheral blood and synovium in rheumatoid arthritis

    PubMed Central

    Shalini P., Usha; Debnath, Tanya; JVS, Vidyasagar; Kamaraju, Suguna R.; Kancherla, Ravindranath; Chelluri, Lakshmi K.

    2016-01-01

    There is an increasing evidence suggesting the role of fork head boxP3 (FoxP3) in the development and the regulation of CD4+CD25+ Treg cells. T-cell regulatory mechanisms in rheumatoid arthritis patients were evaluated by the contributing factors such as pro-inflammatory cytokines, circulating immune complexes, HLA DR expression, ligand binding biomarkers, FoxP3 expression in paired samples of peripheral blood (PB) and synovial fluid (SF). These cellular responses were further correlated with the humoral immune responses such as anti-cyclic citrullinated peptides IgG (CCP), circulating immune complex-c1q IgG (CIC), immunoglobulin G (IgG) and immunoglobulin M (IgM) of the rheumatoid arthritis factor (RAF). The results suggest a definitive role of Tregs in the homeostatic control because there is an increase in FoxP3 (37%) and HLA-DR (45%) expression in the synovial fluid as compared to PB. Furthermore, humoral responses as a downstream effector mechanism are positively correlated with the pathogenesis of rheumatoid arthritis (RA). A positive relationship exists between quantitative anti-CCP production and the expression of HLA-DR. The study relates an increased and pivotal role of B cell activation in the synovial fluid thereby permitting the need to ablate the targeted B cell immune responses. PMID:26862306

  7. Rheumatoid arthritis, the contraceptive pill, and androgens.

    PubMed

    James, W H

    1993-06-01

    Evidence is accumulating that low androgen concentrations are a cause of rheumatoid arthritis. This would explain a number of established features of the epidemiology of the disease. These include: (a) the variation of disease activity with pregnancy; (b) the variation of age at onset by sex; (c) the variation by sex with HLA-B15; (d) the association with bone mineral density; and (e) the differing time trends in incidence rates by sex. It is argued, moreover, that if one makes a plausible assumption--namely, that women who choose oral contraceptives have high androgen concentrations at the time they first make this choice--then an explanation becomes available for the confusion about the relation between rheumatoid arthritis and oral contraception. Grounds are adduced for that assumption. If this line of reasoning is substantially correct it also has implications for the relations between rheumatoid arthritis and smoking and consumption of alcohol. PMID:8323402

  8. An Autopsy Case of Fulminant Amebic Colitis in a Patient with a History of Rheumatoid Arthritis

    PubMed Central

    Kawabe, Naoko; Nagasawa, Miho; Nakanishi, Masako

    2016-01-01

    Generally, amebic colitis is localized around the mucosal membrane and often accompanied by diarrhea and abdominal pain. We describe a patient with a history of rheumatoid arthritis who had received prolonged steroid therapy. The patient complained of breathing difficulties because of rheumatoid lung disease. Although the patient was given antibacterial agent, the symptoms did not improve until death. We did an autopsy and found that he had fulminant amebic colitis, although the patient was not previously examined. Histochemical analysis revealed severe inflammation and full-thickness necrosis of the colon by ameba, suggesting the involvement of ameba in the progression of the overall condition. PMID:27382497

  9. Rheumatoid arthritis in population samples in Iraq.

    PubMed Central

    Al-Rawi, Z S; Alazzawi, A J; Alajili, F M; Alwakil, R

    1978-01-01

    A prevalence survey for rheumatoid arthritis was carried out during the summer of 1975 in persons aged 16 years and over in areas of Iraq representative of differences in geography and ethnicity. Definite rheumatoid arthritis was observed in 1% of the 6999 individuals studied, but differences in occurrence rates in relation to various associated characteristics were not detected. It is concluded that present rheumatological services in Iraq have not developed in response to the magnitude of the existing burden. Morning stiffness was reported fairly frequently by individuals without rheumatoid arthritis, but the significance of this observation is not easy to determine. Raynaud's phenomenon was also recorded, but comparative evaluation of the findings is not possible. PMID:629609

  10. Is patient education helpful in providing care for patients with rheumatoid arthritis? A qualitative study involving French nurses.

    PubMed

    Fall, Estelle; Chakroun, Nadia; Dalle, Nathalie; Izaute, Marie

    2013-09-01

    This French study explored nurses' involvement in patient education for patients with rheumatoid arthritis. The study design was qualitative. Semistructured interviews were conducted with 16 hospital nurses. Data analysis was performed according to Giorgi's descriptive phenomenological method, and supported by specific qualitative analysis software (Sphinx). The results showed the important role of hospital nurses in rheumatoid arthritis care. Patient education is a core part of nurses' work, allowing them to give patients information and emotional support. The interviewees displayed skills in helping patients learn to care for themselves. However, patient education mostly concerned patients who are already committed to their health care. Non-adherent patients warrant special attention; their acceptance of their disease, perceptions about disease and treatment, motivation, and autonomy should be specifically addressed. French nurses could benefit from more training, and could be aided by psychologists. Ambulatory services could also be developed for patient education in France, based on examples from other countries. PMID:23480278

  11. Altered Immunoregulation in Rheumatoid Arthritis: The Role of Regulatory T Cells and Proinflammatory Th17 Cells and Therapeutic Implications

    PubMed Central

    Alunno, Alessia; Caterbi, Sara; Ibba-Manneschi, Lidia; Bistoni, Onelia; Bartoloni, Elena; Valentini, Valentina; Terenzi, Riccardo; Gerli, Roberto

    2015-01-01

    In recent years several studies investigated the role of T lymphocyte subpopulations in the pathogenesis of rheumatoid arthritis (RA). Pathogenic Th17 cells mediate pannus growth, osteoclastogenesis, and synovial neoangiogenesis; hence they are key players in the development of the disease. On the other hand, regulatory T (Treg) cells are a T cell subset whose peculiar function is to suppress autoreactive lymphocytes. The imbalance between Th17 and Treg cells has been identified as a crucial event in the pathogenesis of RA. In addition, the effects of currently employed RA therapeutic strategies on these lymphocyte subpopulations have been extensively investigated. This review article aims to discuss current knowledge on Treg and Th17 cells in RA and possible implications of their therapeutic targeting in this disorder. PMID:25918479

  12. Genetics Home Reference: rheumatoid arthritis

    MedlinePlus

    ... risk factors for rheumatoid arthritis are variations in human leukocyte antigen (HLA) genes , especially the HLA-DRB1 gene. The proteins produced from HLA genes help the immune system distinguish the body's own proteins from proteins made by foreign invaders ( ...

  13. [Guidelines for the management of rheumatoid arthritis].

    PubMed

    Kawahito, Yutaka

    2016-06-01

    In 2014, guidelines for the management of rheumatoid arthritis, was announced from Japan College of Rheumatology. This guideline was made by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method with a concept of "treat to target" led for European and American recommendation of rheumatoid arthritis. It assesses not only evidences but also the balance of desirable and undesirable consequences, values and preferences of the patient, and resource use. It is constructed by evidence summary of 88 clinical questions and 37 recommendations about medication, orthopaedic surgery and rehabilitation. PMID:27311182

  14. Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis.

    PubMed

    Sangueza, Omar P; Caudell, Misty D; Mengesha, Yebabe M; Davis, Loretta S; Barnes, Cheryl J; Griffin, Julia E; Fleischer, Alan B; Jorizzo, Joseph L

    2002-08-01

    Palisaded neutrophilic granulomatous dermatitis (PNGD) is an entity that has not been clearly defined either clinically or histopathologically. It is seen in patients with rheumatoid arthritis and other connective tissue diseases. In the past, many cases of PNGD have been described under several different names including palisaded neutrophilic and granulomatous dermatitis, linear subcutaneous bands, interstitial granulomatous dermatitis with cutaneous cords and arthritis, rheumatoid papules, and Churg-Strauss granuloma. We report 7 additional cases of PNGD. Clinically, 6 patients presented with erythematous to violaceous plaques, papules, and nodules on multiple body sites; one presented with subcutaneous linear bands on the shoulder. Five had rheumatoid arthritis; one had adult-onset Still's disease; and one showed clinical signs of rheumatoid arthritis, although serologically the rheumatoid factor was negative. On histologic examination, a spectrum of changes was observed ranging from urticaria-like infiltrates to leukocytoclastic vasculitis and granuloma annulare with neutrophils. We report these cases to expand the histologic spectrum of this entity and to further delineate the different forms of clinical presentation. PMID:12140472

  15. Macrophage migration inhibitory factor: a potential therapeutic target for rheumatoid arthritis

    PubMed Central

    Kim, Kyoung-Woon; Kim, Hae-Rim

    2016-01-01

    Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients. PMID:27169879

  16. Macrophage migration inhibitory factor: a potential therapeutic target for rheumatoid arthritis.

    PubMed

    Kim, Kyoung-Woon; Kim, Hae-Rim

    2016-07-01

    Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients. PMID:27169879

  17. A Woman with Rheumatoid Arthritis and a Bilateral Fracture of the Proximal Tibia

    PubMed Central

    Hooghof, J. Th. (Arjan); Mellema, Joris J.; Posthumus, Marcel D.; van Raaij, Jos J. A. M.

    2016-01-01

    A 52-year-old woman presented herself with pain on the medial sides of the proximal tibia after a minimal trauma. Conventional X-rays did not show any pathology. However, the MRI showed a bilateral fracture of the proximal tibia. Since the patient was treated with methotrexate due to rheumatoid arthritis, methotrexate osteopathy was considered. Long term treatment with low doses of methotrexate proved to inhibit osteoblast proliferation and may eventually lead to decreased bone formation and osteopenia. On the other hand, immobilization, joint deformities, and steroid treatment are associated with rheumatoid arthritis and are also known risk factors for fractures. The clinical relevance of methotrexate osteopathy still has to be established. However, if a patient treated with methotrexate localizes pain in the tibia, methotrexate osteopathy should be considered. Withdrawal of the drug may improve symptoms. PMID:26981298

  18. 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

  19. A Case of Diverticular Perforation in a Young Patient with Rheumatoid Arthritis on Methotrexate

    PubMed Central

    Chang, Ian; Guggenheim, Carla; Laird-Fick, Heather

    2015-01-01

    Background. Disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), are associated with gastrointestinal toxicity. MTX inhibits dihydrofolate reductase, but it is unclear if polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene predict toxicity. Case. We describe a 33-year-old male with polyarticular rheumatoid arthritis who developed sigmoid diverticular perforation while receiving methotrexate, folic acid, prednisone, and naproxen. He tested heterozygous for the C677T allele MTHFR gene. Discussion. Rheumatoid arthritis and its treatments are associated with increased risk of gastrointestinal disease. In one study, perforation was highest among individuals with concomitant exposure to NSAIDs, nonbiologic DMARDs, and glucocorticoids. Multiple mutations of the MTHFR gene have been identified, but their association with MTX toxicity is unclear. This case adds to a growing body of literature that could help inform the treatment of others in the future. PMID:26064129

  20. Management of cardiovascular risk in patients with rheumatoid arthritis: evidence and expert opinion

    PubMed Central

    van den Oever, Inge A.M.; van Sijl, Alper M.

    2013-01-01

    The risk of cardiovascular morbidity and mortality is increased in rheumatoid arthritis. The classical cardiovascular risk factors, including smoking, hypertension, dyslipidaemia, insulin resistance and diabetes mellitus, obesity and physical inactivity do not appear to explain the excess cardiovascular risk in rheumatoid arthritis, although they do contribute, albeit in a different way or to a lesser extent, to rheumatoid arthritis in comparison with the general population. A very important link between rheumatoid arthritis and cardiovascular disease is inflammation as it plays a key role in all stages of atherosclerosis: from endothelial dysfunction to plaque rupture and thrombosis. It also has an influence on and accentuates some traditional cardiovascular risk factors, such as dyslipidaemia, obesity and insulin resistance. To date, the exact pathophysiologic mechanism by which this relation between cardiovascular disease and rheumatoid arthritis can be explained is not completely clear. Cardiovascular risk management in rheumatoid arthritis is mandatory. Unfortunately, the way this should be done remains a point of discussion. In this review issues regarding cardiovascular risk in rheumatoid arthritis and its management will be addressed, according to evidence presented in the latest studies and our own experience-based opinion. PMID:23904862

  1. People Getting a Grip on Arthritis: A Knowledge Transfer Strategy to Empower Patients with Rheumatoid Arthritis and Osteoarthritis

    ERIC Educational Resources Information Center

    Brosseau, Lucie; Lineker, Sydney; Bell, Mary; Wells, George; Casimiro, Lynn; Egan, Mary; Cranney, Ann; Tugwell, Peter; Wilson, Keith G.; De Angelis, Gino; Loew, Laurianne

    2012-01-01

    Objective: The purpose of this study was twofold. First, to help people with arthritis become aware of and utilize Rheumatoid Arthritis (RA) and Osteoarthritis (OA) Clinical Practice Guidelines (CPGs) as they relate to self-management strategies. Second, to evaluate the impact of specific Knowledge Translation (KT) activities on CPG uptake. More…

  2. Pharmacotherapy Options in Rheumatoid Arthritis

    PubMed Central

    Kumar, Pradeep; Banik, Snehashish

    2013-01-01

    Drugs form the mainstay of therapy in rheumatoid arthritis (RA). Five main classes of drugs are currently used: analgesics, non-steroidal anti-inflammatories (NSAIDs), glucocorticoids, nonbiologic and biologic disease-modifying antirheumatic drugs. Current clinical practice guidelines recommend that clinicians start biologic agents if patients have suboptimal response or intolerant to one or two traditional disease modifying agents (DMARDs). Methotrexate, sulfasalazine, leflunomide and hydroxychloroquine are the commonly used DMARDs. Currently, anti-TNF is the commonly used first line biologic worldwide followed by abatacept and it is usually combined with MTX. There is some evidence that tocilizumab is the most effective biologic as a monotherapy agent. Rituximab is generally not used as a first line biologic therapy due to safety issues but still as effective as anti-TNF. The long term data for the newer oral small molecule biologics such as tofacitinib is not available and hence used only as a last resort. PMID:23997576

  3. Paleopathologic evidence for the evolution of rheumatoid arthritis.

    PubMed

    Klepinger, L L

    1978-01-01

    A human skeleton recovered from a Sicilian archaeological site and dating from the Hellenistic period (330-210 B.C.) presents a pathological pattern suggesting a transition between ankylosing spondylitis and rheumatoid arthritis, providing evidence in support of the hypothesis that rheumatoid arthritis may have recently evolved out of ankylosing spondylitis. PMID:367177

  4. Chlamydial infection preceding the development of rheumatoid arthritis: a brief report.

    PubMed

    Jolly, Meenakshi; Curran, J J

    2004-10-01

    Chlamydia trachomatis-triggered reactive arthritis is a well-documented entity that has been extensively described. We do not have a clear understanding about the inflammatory oligoarthritis associated with the presence of this organism. It is rarely cultured from the synovial fluid, but is usually detectable by molecular biological techniques. Typically, Chlamydia trachomatis causes a sterile but inflammatory oligoarthritis. We report an unusual case of inflammatory monoarthritis in a young woman in whom Chlamydia was isolated from the synovial fluid. This is the first case of documented isolation of Chlamydia from synovial fluid, which subsequently was diagnosed as rheumatoid arthritis. PMID:15459816

  5. Destruction of articular cartilage by alpha2 macroglobulin elastase complexes: role in rheumatoid arthritis

    PubMed Central

    Moore, A.; Appelboam, A.; Kawabata, K.; Da Silva, J. A P; D'Cruz, D.; Gowland, G.; Willoughby, D.

    1999-01-01

    OBJECTIVE—Neutrophil elastase accounts for the ability of some fresh rheumatoid synovial fluids to degrade cartilage matrix in vitro. The aim of this study was to determine if enzyme activity could result from depletion of synovial fluid inhibitors or protection of the enzyme from inhibition.
METHODS—The ability of synovial fluids to inhibit porcine pancreatic elastase was investigated together with chemical pretreatments capable of inactivating alpha1 protease inhibitor (α1PI) or preventing formation of alpha2 macroglobulin (α2M) elastase complexes. Subsequently, complexes of human neutrophil elastase with α2M were prepared and applied to frozen sections of cartilage. Proteoglycan loss was quantified by alcian blue staining and scanning and integrating microdensitometry. Parallel studies were carried out using a low molecular weight chromogenic elastase substrate. The effects of α1PI and SF on these systems were investigated. Finally, synovial fluids were subjected to gel filtration and the fractions assayed for elastase activity. High molecular weight fractions were pooled, concentrated, and tested for their ability to degrade cartilage sections.
RESULTS—All synovial fluids reduced the activity of porcine pancreatic elastase, the inhibition mainly being attributable to α1PI, whereas remaining activity resulted from complexes of elastase with α2M. Complexes of human neutrophil elastase with α2M were shown to cause proteoglycan degradation in frozen sections of human articular cartilage. Alpha1PI prevented α2M elastase complexes from degrading cartilage but not the chromogenic substrate. The data suggested that α1PI does not inhibit elastase bound to α2M but sterically hinders the complex. However, only one of five synovial fluids was able to completely block the actions of α2M elastase complexes against cartilage. Gel filtration of rheumatoid synovial fluids showed elastase and cartilage degrading activity to be associated with fractions that

  6. [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. PMID:18159206

  7. Treatment of rheumatoid arthritis using photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hendrich, Christian; Diddens, Heyke C.; Nosir, Hany R.; Siebert, Werner E.

    1995-03-01

    The only early therapy of rheumatoid arthritis in orthopedic surgery is a synovectomy, which is restricted to more or less big joints. A laser-synovectomy of small joints is ineffective yet. An alternative method may be photodynamic therapy. In our study we describe the photodynamic effect of Photosan 3 in a cell culture study.

  8. Segmental vitiligo after infliximab use for rheumatoid arthritis - A case report*

    PubMed Central

    Carvalho, Clarissa Luiza Dalla Bernardina; Ortigosa, Luciena Cegatto Martins

    2014-01-01

    The tumor necrosis factor alpha is a cytokine related to immune and inflammatory processes by acting on different parts of the body. It is secreted by several cell types including macrophages, lymphocytes, monocytes, neutrophils, dendritic cells, among others. Infliximab is a chimeric monoclonal antibody that specifically binds to soluble and transmembrane tumor necrosis factor alpha form blocking its action. In rheumatoid arthritis it is used because the cytokines that cause inflammation in this disease are regulated by tumor necrosis factor alpha and IL-1. We report the case of a 46-year-old patient with rheumatoid arthritis who developed segmental vitiligo after two months using infliximab. The event aims to alert to the existence of this adverse effect that can be induced with the use of this medication. PMID:24626663

  9. Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis*

    PubMed Central

    Dias, Olívia Meira; Pereira, Daniel Antunes Silva; Baldi, Bruno Guedes; Costa, André Nathan; Athanazio, Rodrigo Abensur; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2014-01-01

    The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD. PMID:24626274

  10. Nanofacilitated synergistic treatment for rheumatoid arthritis: A 'three-pronged' approach.

    PubMed

    Pandey, Shweta; Rai, Nishant; Rawat, Purnima; Ahmad, Farhan Jalees; Talegaonkar, Sushama

    2016-07-01

    Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease of unidentified etiology that affects the joints and causes pain, swelling, stiffness and redness in the joints. The exact cause of rheumatoid arthritis has not yet been discovered and, consequently, treatment methods have not been optimally effective. It has long been treated with anti-inflammatory and immunosupressants including modern biologics either alone or in combination but all of the drugs have severe life threatening consequences with impaired immune function due to nonspecific targeting. Therefore, a three-pronged approach of local, active and synergistic targeting can be used to optimize delivery of therapeutic agents to reduce toxicity and patient outcome without compromising patient's immunity. PMID:27241253

  11. Wrist arthrodesis in rheumatoid arthritis. A comparison of two methods of fusion.

    PubMed

    Howard, A C; Stanley, D; Getty, C J

    1993-06-01

    17 wrists were arthrodesed in 13 patients with severe wrist disease due to rheumatoid arthritis. Eight fusions in seven patients were carried out using a radial sliding bone graft technique whilst nine fusions in nine patients were undertaken using a third tubular AO plate. Subjective, objective and radiological assessments confirmed the efficacy of both methods but indicated a shorter period of post-operative immobilization for patients treated using the AO plate fixation technique. The importance of this is discussed. PMID:8345273

  12. Role of the netrin system of repellent factors on synovial fibroblasts in rheumatoid arthritis and osteoarthritis.

    PubMed

    Schubert, T; Denk, A; Mägdefrau, U; Kaufmann, S; Bastone, P; Lowin, T; Schedel, J; Bosserhoff, A K

    2009-01-01

    Changes in the expression of repellent factors, i.e., Netrins and their receptors, may be responsible for the invasive behavior of the synovial tissue cells in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). This study was carried out to analyze the expression of Netrins and their receptors in synovial cells of patients with RA, OA, and control subjects without synovial inflammation. Quantitative RT-PCR was performed to measure the expression of Netrin-1, -3, -4, Neogenin, DCC, UNC5A-D. The influence of Netrin-1 on synovial fibroblasts (SF) was analyzed by determining proliferation, migration, and their ability to organize collagen. SF expressed all repellent factors of the Netrin family. When comparing SF of healthy donors to patients with RA and OA, a stronger expression of UNC5B (4 fold) and UNC5C (769 fold) in RA and OA was found, whereas expression of the other molecules revealed no significant differences. Treating the SF-cells with recombinant Netrin-1 resulted in inhibition of migration of RA- and OA-SFs whereas control cells were not affected. The stronger expression of UNC5B and UNC5C receptors might contribute to the disordered phenotype of RA- and OA-SFs. Addition of Netrin-1 reduces the migratory ability of SFs, potentially by repulsion, as seen in neuronal cells in embryonic development. Due to its function, Netrin-1 may constitute a novel target in the treatment of OA and RA. PMID:19822088

  13. Diet therapy for rheumatoid arthritis.

    PubMed

    Panush, R S; Carter, R L; Katz, P; Kowsari, B; Longley, S; Finnie, S

    1983-04-01

    Although diet therapy for arthritis has received considerable publicity, there is little objective information about its efficacy. We undertook a 10-week, controlled, double-blind, randomized trial of patients with active rheumatoid arthritis (RA). Twenty-six patients completed the study; 11 were on an experimental diet (a specific popular diet free of additives, preservatives, fruit, red meat, herbs, and dairy products) and 15 were on a "placebo" diet. Of 183 variables analyzed, there were no clinically important differences among rheumatologic, laboratory, immunologic, radiologic, or nutritional findings between patients on experimental and placebo diets. Six RA patients on the placebo and 5 on the experimental diet improved by objective criteria. Improvement averaged 29% for patients on placebo and 32% for patients on experimental diets. Two patients on the experimental diet improved notably, elected to remain on the experimental diet following the study period, have continued to improve, and noted exacerbations of disease upon consuming nonexperimental diet foods. Our study failed to provide evidence of objective overall clinical benefit of this diet as followed by a group of patients with longstanding, progressive, active RA. However, our data are not inconsistent with the possibility that individualized dietary manipulations might be beneficial for selected patients with rheumatic disease. PMID:6838671

  14. Silicone Arthroplasty After Ankylosis of Proximal Interphalangeal Joints in Rheumatoid Arthritis: A Case Report.

    PubMed

    Awan, Hisham M; Imbriglia, Joseph E

    2016-01-01

    Rheumatoid arthritis (RA) can cause severe disability of the hand and fingers. Ankylosis of the finger joints is a known yet underreported manifestation of RA of the hand. We report the case of a patient who had RA and developed autofusion of the proximal interphalangeal (PIP) joints. At presentation, the PIP joints were fused in 15° of flexion. Silicone PIP arthroplasty was performed. Function improved with 60° of PIP joint motion and no pain. PMID:27327930

  15. Effect of nonsurgical periodontal treatment in patients with periodontitis and rheumatoid arthritis: A systematic review

    PubMed Central

    Silvestre-Rangil, Javier; Bagan, Leticia; Bagan, Jose V.

    2016-01-01

    Background Periodontitis has been regarded as a potential risk factor for rheumatoid arthritis (RA). A systematic review is made to determine whether nonsurgical periodontal treatment in patients with RA offers benefits in terms of the clinical activity and inflammatory markers of the disease. Material and Methods A search was made of the Medline-PubMed, Cochrane, Embase and Scopus databases to identify studies on the relationship between the two disease processes, and especially on the effects of nonsurgical treatment in patients of this kind. The search was based on the following keywords: rheumatoid arthritis AND periodontitis (MeSH), rheumatoid arthritis AND periodontal treatment. Results Eight articles on the nonsurgical treatment of patients with periodontitis and RA were finally included in the study. All of them evaluated clinical (DAS28) and laboratory test activity (ESR, CRP, IL-6, TNFα) before and after treatment. A clear decrease in DAS28 score and ESR was recorded, while other parameters such as CRP, IL-6 and TNFα showed a non significant tendency to decrease as a result of treatment. Conclusions Nonsurgical treatment improved the periodontal condition of patients with periodontitis and RA, with beneficial effects upon the clinical and laboratory test parameters (DAS28 and ESR), while other inflammatory markers showed a marked tendency to decrease. However, all the studies included in the review involved small samples sizes and follow-up periods of no more than 6 months. Larger and particularly longitudinal studies are therefore needed to more firmly establish possible significant relations between the two disease processes. Key words:Periodontitis, rheumatoid arthritis, periodontal treatment. PMID:26946202

  16. Inflammatory infratentorial progressive multifocal leukoencephalopathy in a patient with rheumatoid arthritis.

    PubMed

    Lach, Boleslaw; Connolly, Barbara; Wüthrich, Christian; Koralnik, Igor J

    2014-02-01

    An 84-year-old man with rheumatoid arthritis (RA) treated with methotrexate, developed progressive confusion and cerebellar symptoms, and died approximately 2 months later. Neuropathological examination revealed progressive multifocal leukoencephalopathy (PML) involving the cerebellum and brainstem. The affected tissues displayed intense infiltrations by CD8+ T-cells and microglia. JC virus was localized in oligodendroglia and cerebellar granule cells. This case illustrates unusual localization of inflammatory PML in a patient with RA treated with methotrexate. PMID:23683127

  17. Persistence of babesiosis for >2 years in a patient on rituximab for rheumatoid arthritis.

    PubMed

    Raffalli, John; Wormser, Gary P

    2016-06-01

    We report a patient who was being treated with rituximab for rheumatoid arthritis who developed Babesia microti infection that persisted for 26 months despite prolonged anti-babesia drug therapy. The explanation for the persistence was likely to have been the long-term immunocompromising effects of rituximab, as evidenced by seronegativity for B. microti antibodies that lasted for more than 1 year after onset of infection. PMID:27036977

  18. THE IDENTIFICATION OF A FLUORESCENT REDUCING SUBSTANCE IN THE URINE OF PATIENTS WITH RHEUMATOID ARTHRITIS

    PubMed Central

    McMillan, Mary

    1960-01-01

    The report that 2,5-dihydroxyphenylpyruvic acid occurs in the urine of patients with collagen disease has not been confirmed, and no evidence was found for regarding collagen disease as being due to an inherent error in tyrosine metabolism as suggested by Japanese workers. A strongly reducing substance was conspicuous in the urine of patients with rheumatoid arthritis but not in that of normal persons. This substance was identified as 3-hydroxyanthranilic acid (3-HAA). A method is described for the measurement of 3-HAA in urine, employing ether extraction, paper chromatography in a formate solvent, and visual assessment by fluorescence in ultra-violet light and colour with Ehrlich's reagent. Normal persons excreted from less than 125 to 375 μg./day (average rather lower than 200 μg./day); those suffering from rheumatoid arthritis excreted from less than 125 to 2,250 μg./day (average 820 μg./day). The excessive excretion of 3-HAA in persons with rheumatoid arthritis was investigated in terms of other aspects of the activity of the disease. Some relationship was suggested between excretion levels, the erythrocyte sedimentation rate, and the sensitized sheep cell test. Cases of osteoarthritis, other orthopaedic conditions, and miscellaneous diseases were examined. A few of the latter, including diseases of the haemopoietic system, were associated with increased excretion of 3-HAA. PMID:16810953

  19. Bilateral Terrien’s Marginal Degeneration and Posterior Polymorphous Dystrophy in a Patient with Rheumatoid Arthritis

    PubMed Central

    Zarei-Ghanavati, Siamak; Javadi, Mohammad-Ali; Yazdani, Shahin

    2012-01-01

    Purpose: To report an interesting case of concomitant bilateral Terrien’s marginal degeneration-like corneal ectasia and posterior polymorphous corneal dystrophy in a young man with quiescent rheumatoid arthritis. Case Report: A 24-year-old man with history of rheumatoid arthritis presented with bilateral decreased vision since four years ago. Slit lamp examination revealed bilateral circumferential peripheral corneal thinning and bulging with vascularization and lipid deposition in addition to band-like lesions in descemet’s membrane. Previous records revealed no gross corneal abnormalities up to 4 years ago. Corneal lesions were compatible with bilateral circumferential Terrien’s marginal degeneration concomitant with posterior polymorphous dystrophy. Conclusion: To our knowledge, this is the first report of concomitant bilateral Terrien’s marginal degeneration with peripheral corneal ectasia and posterior polymorphous dystrophy in a patient with rheumatoid arthritis. Bilateral circumferential involvement, younger age at presentation and total peripheral corneal ectasia as observed in this case are not typical for classic Terrien’s marginal degeneration. PMID:22737388

  20. 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

  1. C5orf30 is a negative regulator of tissue damage in rheumatoid arthritis.

    PubMed

    Muthana, Munitta; Hawtree, Sarah; Wilshaw, Adam; Linehan, Eimear; Roberts, Hannah; Khetan, Sachin; Adeleke, Gbadebo; Wright, Fiona; Akil, Mohammed; Fearon, Ursula; Veale, Douglas; Ciani, Barbara; Wilson, Anthony G

    2015-09-15

    The variant rs26232, in the first intron of the chromosome 5 open reading frame 30 (C5orf30) locus, has recently been associated with both risk of developing rheumatoid arthritis (RA) and severity of tissue damage. The biological activities of human C5orf30 are unknown, and neither the gene nor protein show significant homology to any other characterized human sequences. The C5orf30 gene is present only in vertebrate genomes with a high degree of conservation, implying a central function in these organisms. Here, we report that C5orf30 is highly expressed in the synovium of RA patients compared with control synovial tissue, and that it is predominately expressed by synovial fibroblast (RASF) and macrophages in the lining and sublining layer of the tissue. These cells play a central role in the initiation and perpetuation of RA and are implicated in cartilage destruction. RASFs lacking C5orf30 exhibit increased cell migration and invasion in vitro, and gene profiling following C5orf30 inhibition confirmed up-regulation of genes involved in cell migration, adhesion, angiogenesis, and immune and inflammatory pathways. Importantly, loss of C5orf30 contributes to the pathology of inflammatory arthritis in vivo, because inhibition of C5orf30 in the collagen-induced arthritis model markedly accentuated joint inflammation and tissue damage. Our study reveal C5orf30 to be a previously unidentified negative regulator of tissue damage in RA, and this protein may act by modulating the autoaggressive phenotype that is characteristic of RASFs. PMID:26316022

  2. Why do we need new treatments for rheumatoid arthritis?

    PubMed

    Chikanza, I C; Jawed, S; Naughton, D; Blake, D R

    1998-04-01

    Rheumatoid arthritis is a chronic systemic autoimmune inflammatory disease characterized by progressive joint damage. The classical treatments of the disease such as myocrisin and sulphasalazine, are not always effective at controlling the disease. This has necessitated the development of novel agents for treating rheumatoid arthritis. Most of these drugs are biological in nature and are targeted at specific sites of the inflammatory cascade of reactions. A number of clinical trials have been conducted. The clinical effects that have been observed are transient, necessitating repeated treatments and the risk of vaccination effects. Many of these agents have to be administered parenterally, production costs are very high. Consequently, chemical entities which can be taken orally need to be developed. Since the immune system is very complex with pleiotropic cytokines and redundancy in some of the regulatory networks, it may therefore be necessary to use multiple agents targeted at different specific sites of the inflammatory cascade or that different agents could be given at different stages of the disease, to induce disease remission and maintain the response to therapy. Cytokines such as tumour necrosis factor (TNF) and interleukin 1 (IL-1) play important physiological roles in the host's defence systems against infections and malignancy. The chronic inhibition of these cytokines by targeted therapies may therefore lead to the development of side effects. Thus, carefully controlled long-term studies will be required to assess the safety of selective targeting of processes involved in inflammation. A more recent novel approach is to target hypoxic tissues with bioreductive agents. Thus, some of the established rheumatoid arthritis treatments could be linked to bioreductive agents and released in hypoxic tissues where inflammation is occurring. This review summarizes the important developments in the therapy of rheumatoid arthritis. There is no doubt that despite

  3. Risk of Major Cardiovascular Events in Patients with Psoriatic Arthritis, Psoriasis and Rheumatoid Arthritis: A population-based cohort study

    PubMed Central

    Yu, YiDing; Haynes, Kevin; Love, Thorvardur Jon; Maliha, Samantha; Jiang, Yihui; Troxel, Andrea B.; Hennessy, Sean; Kimmel, Stephen E.; Margolis, David J.; Choi, Hyon; Mehta, Nehal N.; Gelfand, Joel M.

    2015-01-01

    Objectives We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and psoriasis without known PsA compared to the general population after adjusting for traditional cardiovascular risk factors. Methods A population-based longitudinal cohort study from 1994–2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the United Kingdom. Patients aged 18–89 with PsA, RA, or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents, and the composite outcome (MACE). Cox proportional hazards models were used to calculate the hazard ratios (HR) for each outcome adjusted for traditional risk factors. A priori we hypothesized an interaction between disease status and disease modifying anti-rheumatic drug (DMARD) use. Results Patients with PsA (N=8,706), RA (N=41,752), psoriasis (N=138,424) and unexposed controls (N=81,573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in PsA patients not prescribed a DMARD (HR 1.24, 95%CI: 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95%CI: 1.28 to 1.50, DMARD: HR 1.58, 95%CI: 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95%CI: 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95%CI: 1.17 to 1.73). Conclusions Cardiovascular risk should be addressed with all patients affected by psoriasis, psoriatic arthritis or rheumatoid arthritis. PMID:25351522

  4. 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

  5. Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis

    PubMed Central

    Harle, P; Pongratz, G; Weidler, C; Buttner, R; Scholmerich, J; Straub, R

    2004-01-01

    Background: Hypoandrogenicity is common in obesity and in chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Adrenal androgens such as androstenedione (ASD) and dehydroepiandrosterone (DHEA) sulphate are low, which partly depends on the influence of TNF in chronic inflammatory diseases. Leptin is stimulated by TNF and is associated with hypoandrogenicity in non-inflammatory conditions. Objective: To study the interrelation between serum levels of leptin and adrenal steroids in SLE and RA. Methods: In a retrospective study, serum levels of leptin, ASD, DHEA, and 17-hydroxyprogesterone (17OHP) were measured by ELISA, and serum levels of cortisol by radioimmunoassay in 30 patients with RA, 32 with SLE, and 54 healthy control subjects (HS). Results: In SLE and RA but not HS, serum levels of ASD correlated negatively with serum levels of leptin (p<0.01) independently of prior prednisolone treatment in patients with SLE (p = 0.013) and tended to be independent of prednisolone in patients with RA (p = 0.067). In a partial correlation analysis, this interrelation remained significant after controlling for daily prednisolone dose in both patient groups. In both patient groups, serum leptin levels correlated negatively with the molar ratio of serum ASD/serum cortisol and serum ASD/serum 17OHP, and positively with the molar ratio of serum DHEA/serum ASD. Conclusions: The negative correlation of serum leptin and ASD or, particularly, ASD/17OHP, together with its known anti-androgenic effects indicate that leptin is also involved in hypoandrogenicity in patients with SLE and RA. Leptin may be an important link between chronic inflammation and the hypoandrogenic state. PMID:15194576

  6. A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

    PubMed Central

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A2AAR stimulation in a rat model of arthritis. We investigated A2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A2AARs in lymphocytes from RA patients. The effectiveness of A2AAR stimulation in a rat model of arthritis supported the role of A2AAR agonists as potential pharmacological treatment for RA. PMID:23326596

  7. T Cell Migration in Rheumatoid Arthritis

    PubMed Central

    Mellado, Mario; Martínez-Muñoz, Laura; Cascio, Graciela; Lucas, Pilar; Pablos, José L.; Rodríguez-Frade, José Miguel

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies. PMID:26284069

  8. T Cell Migration in Rheumatoid Arthritis.

    PubMed

    Mellado, Mario; Martínez-Muñoz, Laura; Cascio, Graciela; Lucas, Pilar; Pablos, José L; Rodríguez-Frade, José Miguel

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies. PMID:26284069

  9. Interleukin-17 as a novel predictor of vascular function in rheumatoid arthritis

    PubMed Central

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Yalavarthi, Srilakshmi; Lustig, Susan; Brook, Robert; Kaplan, Mariana J.

    2011-01-01

    Objectives Rheumatoid arthritis (RA) is associated with enhanced cardiovascular (CV) risk and subclinical vascular disease. The proinflammatory milieu has been linked to premature atherosclerosis and endothelial dysfunction in RA. While IL-17 is considered pathogenic in RA, its role in determining vascular dysfunction in this disease has not been systematically assessed. We analyzed candidate variables that could determine endothelial function in various vascular territories in a cohort of RA patients on biologic therapy, with minimal traditional CV risk factors and low disease activity score. Methods RA patients (n=51) on stable biologic therapy underwent measurement of conduit artery endothelial function by brachial artery flow-mediated dilatation (FMD); arterial compliance by pulse wave velocity (PWV) assessment; and endothelium-dependent microvascular testing with Endo-PAT2000 device to assess reactive hyperemia index (RHI). IL-17 was quantified by ELISA and disease activity was assessed by DAS-28. Results IL-17 and high sensitivity CRP were the main determinants of lower RHI in univariate (p=0.004, <0.001) and multivariate (p=0.004, <0.0001) analysis, respectively. Traditional and non-traditional CV risk variables determined PWV, with a significant positive association with IL-17 in univariate and multivariate analysis (p=0.02, 0.01, respectively). In contrast, conduit endothelial function was mainly determined by rheumatoid factor titers (p=0.003). Anti-CCP titers and disease activity did not determine vascular function. Conclusion In RA patients treated with biologics, IL-17 is a main predictor of microvascular function and arterial compliance. This study suggests IL-17 may play a significant role in development of endothelial dysfunction and CVD in RA. PMID:21727237

  10. Can Rheumatoid Arthritis Be Prevented?

    PubMed Central

    Deane, Kevin

    2013-01-01

    The discovery of elevations of rheumatoid arthritis (RA)-related biomarkers prior to the onset of clinically apparent RA raises hopes that individuals who are at risk for future RA can be identified in a preclinical phase of disease that is defined as abnormalities of RA-related immune activity prior to the clinically apparent onset of joint disease. Additionally, there is a growing understanding of the immunologic processes that are occurring in preclinical RA, as well as a growing understanding of risk factors that may be mechanistically related to RA development. Furthermore, there are data supporting that treatment of early RA can lead to drug free remission. Taken as a whole, these findings suggest that it may be possible to use biomarkers and other factors to accurately identify the likelihood and timing of onset of future RA, and intervene with immunomodulatory therapies and/or risk factor modification to prevent the future onset of RA in at-risk individuals. Importantly, several clinical prevention trials for RA have already been tried, and one is underway. However, while our understanding of the growing understanding of the mechanisms and natural history of RA development may be leading us to the implementation of prevention strategies for RA, there are still several challenges to be met. These include developing sufficiently accurate methods of predicting those at high risk for future RA so that clinical trials can be developed based on accurate rates of development of arthritis and subjects can be adequately informed of their risk for disease, identifying the appropriate interventions and biologic targets for optimal prevention, and addressing the psychosocial and economic aspects that are crucial to developing broadly applicable prevention measures for RA. These issues notwithstanding, prevention of RA may be within reach in the near future. PMID:24315049

  11. Rheumatoid Arthritis and Incidence of Twelve Initial Presentations of Cardiovascular Disease: A Population Record-Linkage Cohort Study in England

    PubMed Central

    Pujades-Rodriguez, Mar; Duyx, Bram; Thomas, Sara L.; Stogiannis, Dimitris; Rahman, Anisur; Smeeth, Liam; Hemingway, Harry

    2016-01-01

    Introduction 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. Methods 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. Results 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. Conclusions 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. PMID:26978266

  12. Recurrent Pneumothorax after Etanercept Therapy in a Rheumatoid Arthritis Patient: A Case Report

    PubMed Central

    Kim, Sang Hoon; Seo, Young Ho; Kim, Ji Hyoung; Jeong, Il Woo; Sohn, Sung Birm

    2014-01-01

    The use of anti-tumor necrosis factor (anti-TNF) agents for rheumatoid arthritis (RA) patients who are refractory to disease-modifying anti-rheumatic drugs is gradually increasing. Etanercept is the first anti-TNF agent to be approved for RA treatment and is also the most widely used. However, aggravation of interstitial lung disease after etanercept treatment in RA patients has been reported recently. We report the first case of recurrent spontaneous pneumothorax with progression of interstitial lung disease after initiating etanercept therapy. The withdrawal of etanercept and a change to adalimumab, a different class of TNF inhibitor, achieved clinical stabilization. PMID:25568848

  13. Morbidity impact of rheumatoid arthritis on society.

    PubMed

    McDuffie, F C

    1985-01-21

    Classic and definite rheumatoid arthritis affects from 0.5 to 1 percent of the United States' population between the ages of 20 and 80. In the age group of 55 to 75 years, this figure increases to 4.5 percent. In addition to the pain and suffering produced by this disease, family structure is dramatically affected--the divorce rate for patients with rheumatoid arthritis is 70 percent above that for the general population. Rheumatoid arthritis also results in serious economic loss to society. In 1983, the direct cost (out-of-pocket expense for medical care) was $777 million, and the indirect cost (loss of productivity) was $215 million, with a total of approximately $1 billion. The average person with stage III rheumatoid arthritis suffers a 60 percent decline in earnings during the first six years after onset of the disease. Recent studies have indicated that the ability to remain employed depends at least as much on job-related factors as on the extent of disease or success of medical treatment. Job autonomy or the ability to control one's working conditions is the most important factor. Other important variables are education, seniority, and work that is not excessively physically demanding. Good transportation between home and job is also an essential requirement for remaining employed. There are few data available on the cost/benefit ratio of the treatment of rheumatoid arthritis. An 18-month study showed a trend toward greater improvement in patients given optimal care by a team of experts in a medical center as compared with average treatment provided in the community. A study in Scotland on cost of hospitalization of 366 patients (about one half underwent surgery) showed cost benefits of xi 14,000 to xi 131,000 over a five- to 10-year period for those who returned to work. Patients who did not return to work incurred medical costs of xi 100,000. There is little question that more effective medical treatment and better rehabilitation strategies for people

  14. Diagnosis and classification of rheumatoid arthritis.

    PubMed

    Kourilovitch, Maria; Galarza-Maldonado, Claudio; Ortiz-Prado, Esteban

    2014-01-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease of unclear etiology that is manifested in by a progressive and destructive polyarthritis in association with serological evidence of autoreactivity. Its diagnosis is based on the classification criteria that involve four parameters: joint involvement, serology (rheumatoid factor and anti-cyclic citrullinated peptide--anti-CCP), levels of acute phase reactants and the duration of the symptoms Aletaha, et al. [1]. This classification simplifies the categorization of the patients with early RA; however, the diagnosis requires highly trained specialists who are able to differentiate early symptoms of RA from other pathologies. PMID:24568777

  15. [The pulmonological manifestations of rheumatoid arthritis].

    PubMed

    Bernscherer, György; Karabélyos, Csaba; Tarján, Zsolt

    2008-07-20

    In their review article the authors overview the primary and secondary pulmonary complications of rheumatoid arthritis with the help of bibliographic data. They emphasize the pulmonological complications of disease modifying antirheumatic drugs used for the pharmaceutical therapy of rheumatoid arthritis, of which they discuss the methotrexate induced pulmonary diseases. Methotrexate participates nearly in all of additive double and triple--O'Dell-scheme--combined disease modifying antirheumatic drugs therapy. Because of that, the early detection of drug-induced pulmonological complications is important. For rheumatologists the treatment of methotrexate resistant rheumatoid arthritis is always getting a higher and higher challenge. Biological therapeutical drugs act as cytokine antagonists, by blocking TNF-alpha and, compared to disease modifying antirheumatic drugs, they can more effectively inhibit the progression of the disease. These are the biological response modifiers. Their main representatives are infliximab, adalimumab, and etanercept. At the end, the authors discuss secondary pulmonary complications caused by biological response modifiers, e.g. the biological response modifiers associated pulmonary tuberculosis, bacterial tracheobronchitis, bacterial pneumonia, bronchiectasia, pulmonary oedema, rapid fibrosing alveolitis, and coccidioidomycosis. At 3% of patients with rheumatoid arthritis, treated with biological response modifiers, who live in Arizona, California, Nevada, pulmonary and systemic mycosis--coccidioidomycosis can appear with a 15% of mortality. As a consequence of frequent earthquakes, the spores getting into the air from the ground infect immunosuppressed patients treated with biological response modifiers. The authors draw attention to the fact that patients who receive biological therapy and travel to the above-mentioned endemic or earthquake-active regions, have a potential high risk, so it is indispensable that they are informed by the

  16. Risks and benefits of low-dosage cyclosporin in rheumatoid arthritis.

    PubMed

    Pasero, G; Ferraccioli, G F; Portioli, I

    1997-05-01

    The effects of cyclosporin on the activity of rheumatoid arthritis have mainly been investigated in patients with active, refractory, long-standing disease. The data obtained in these trials suggest that cyclosporin is not only a symptomatic treatment for rheumatoid arthritis but can also be considered a disease-modifying antirheumatic drug (DMARD), since it seems to be capable of slowing the progression of cartilage and bone damage due to rheumatoid arthritis. The trials conducted so far have led to a better understanding of cyclosporin toxicity and, therefore, to better monitoring of patients in order to avoid it. The reasons for studying the role of cyclosporin in patients with early, active and potentially severe rheumatoid arthritis are the poor prognosis of the disease despite the use of the presently available DMARDs, and the hypothesis that the drug is more efficacious and better tolerated in early rheumatoid arthritis. A new classification of antirheumatic drugs proposes that disease-controlling antirheumatic therapies decrease inflammatory synovitis and prevent structural joint damage or significantly reduce its rate of progression. However, few existing drugs meet these criteria. The 12-month results of a disease-controlling antirheumatic therapy clinical trial with a blinded radiological end-point, named GRISAR (Gruppo Reumatologi Italiani Studio Artrite Reumatoide) comparing cyclosporin with conventional DMARDs in patients with early rheumatoid arthritis provide strong evidence that cyclosporin offers better control of ongoing joint damage than do conventional DMARDs. PMID:18031101

  17. Cervical spine involvement as initial manifestation of rheumatoid arthritis: a case report.

    PubMed

    Araújo, Filipe; Silva, Inês; Sepriano, Alexandre; Reizinho, Carla; Marques, Luís; Nero, Patrícia; Branco, Jaime C

    2015-01-01

    Rheumatoid arthritis' synovitis affects mostly small hand and feet joints, although it may compromise any joint with a synovial lining. Cervical involvement occurs usually in longstanding disease in over half of these patients. We report the case of a 35-year old male patient who was referred to our outpatient clinic for a 2-year severe and disabling inflammatory neck pain, with incomplete response to intramuscular non-steroidal anti-inflammatory drugs and unremarkable cervical imaging studies. He also mentioned self-limited episodes of symmetric polyarthralgia involving hands, wrists, elbows, knees and feet, which started after his cervical complaints. On laboratorial workup, positive rheumatoid factor and anti-citrullinated peptide antibody and negative HLA-B27 were found. Cervical spine magnetic resonance imaging revealed atlantoaxial subluxation and odontoid process inflammatory pannus and erosions. Rheumatoid arthritis with cervical spine involvement as initial manifestation of disease was the definite diagnosis. The patient was started on methotrexate and prednisone and he was referred to neurosurgery outpatient clinic for cervical spine fixation. PMID:24861079

  18. Differentially expressed epigenome modifiers, including Aurora kinase A and B, in immune cells of rheumatoid arthritis

    PubMed Central

    Glant, Tibor T.; Besenyei, Timea; Kádár, András; Kurkó, Júlia; Tryniszewska, Beata; Gál, János; Soós, Györgyi; Szekanecz, Zoltán; Hoffmann, Gyula; Block, Joel A.; Katz, Robert S.; Mikecz, Katalin; Rauch, Tibor A.

    2014-01-01

    Objective The aim of this study was to identify epigenetic factors that are implicated in the pathogenesis of rheumatoid arthritis (RA) and to explore the therapeutic potential of the targeted inhibition of these factors. Methods PCR arrays were utilized to investigate the expression profile of genes that encod key epigenetic regulator enzymes. Mononuclear cells from RA patients and mice were monitored for gene expression changes, in association with arthritis development in murine models of RA. Selected genes were further characterized by quantitative real-time PCR, Western blot and flow cytometry methods. The targeted inhibition of the upregulated enzymes was studied in arthritic mice. Results A set of genes with arthritis-specific expression was identified by the PCR arrays. Aurora kinase A and B, both of which were highly expressed in arthritic mice and treatment naïve RA patients, were selected for detailed analysis. Elevated Aurora kinase expression was accompanied with an increased phosphorylation of histone H3, which promotes proliferation of T lymphocytes. Treatment with VX-680, a pan-Aurora kinase inhibitor, promoted B cell apoptosis, provided significant protection against the onset, and attenuated the inflammatory reactions in arthritic mice. Conclusions Arthritis development is accompanied the changes in the expression of a number of epigenome-modifying enzymes. Drug-induced downregulation of the Aurora kinases, among other targets, seems to be sufficient to treat experimental arthritis. Development of new therapeutics that target the Aurora kinases can potentially improve RA management. PMID:23653330

  19. Genetic epidemiology of rheumatoid arthritis.

    PubMed Central

    Lynn, A H; Kwoh, C K; Venglish, C M; Aston, C E; Chakravarti, A

    1995-01-01

    We conducted family studies and segregation analyses of rheumatoid arthritis (RA) that were based on consecutive patients with RA ascertained without regard to family history or known risk factors. First-degree relatives from 135 simplex and 30 multiplex families were included in the analyses. A highly penetrant recessive major gene, with a mutant allele frequency of .005, was identified as the most parsimonious genetic risk factor. Significant evidence for heterogeneity in risk for RA was observed for proband gender but not for proband age at onset. Kaplan-Meier risk analysis demonstrated significant evidence for differences in the distribution of risk among first-degree relatives. These analyses demonstrated that both proband gender and age at onset are important risk factors but that proband gender appears to be the more important determinant of risk, with relatives of male probands having the greatest cumulative risk for RA. In addition, log-linear modeling identified proband gender, familiality (multiplex or simplex), and an interaction term between these two variables as being adequate to define the distribution of risk in families. The pattern of risk for RA among susceptible individuals and its inheritance is thus heterogeneous. For future genetic analyses, families with an excess of affected males having a young age at onset may be the most informative in identifying the putative recessive gene and its modifiers. PMID:7611283

  20. Structural requirements for recognition of the HLA-Dw14 class II epitope: A key HLA determinant associated with rheumatoid arthritis

    SciTech Connect

    Hiraiwa, Akikazu; Yamanaka, Katsuo; Kwok, W.W.; Nepom, G.T. ); Mickelson, E.M.; Masewicz, S.; Hansen, J.A. ); Radka, S.F. )

    1990-10-01

    Although HLA genes have been shown to be associated with certain diseases, the basis for this association is unknown. Recent studies, however, have documented patterns of nucleotide sequence variation among some HLA genes associated with a particular disease. For rheumatoid arthritis, HLA genes in most patients have a shared nucleotide sequence encoding a key structural element of an HLA class II polypeptide; this sequence element is critical for the interaction of the HLA molecule with antigenic peptides and with responding T cells, suggestive of a direct role for this sequence element in disease susceptibility. The authors describe the serological and cellular immunologic characteristics encoded by this rheumatoid arthritis-associated sequence element. Site-directed mutagenesis of the DRB1 gene was used to define amino acids critical for antibody and T-cell recognition of this structural element, focusing on residues that distinguish the rheumatoid arthritis-associated alleles Dw4 and Dw14 from a closely related allele, Dw10, not associated with disease. Both the gain and loss of rheumatoid arthritis-associated epitopes were highly dependent on three residues within a discrete domain of the HLA-DR molecule. Recognition was most strongly influenced by the following amino acids (in order): 70 > 71 > 67. Some alloreactive T-cell clones were also influenced by amino acid variation in portions of the DR molecule lying outside the shared sequence element.

  1. Unmet needs in rheumatoid arthritis.

    PubMed

    Bykerk, Vivian

    2009-06-01

    Despite recent advances in the treatment of rheumatoid arthritis (RA), including the introduction of biologic therapies and employment of combination disease-modifying antirheumatic drug (DMARD) strategies, remission rates remain suboptimal and patients with RA are still missing a significant number of work days. Early diagnostic criteria are needed to ensure that appropriate treatment is initiated early so as to prevent joint damage. Better prognostic markers are also needed to identify patients with the potential for poor outcomes, in whom more aggressive strategies can be applied at the outset. Because of stringent inclusion criteria and heterogeneous definitions of remission, results seen in clinical trials of RA are not necessarily generalizable to results seen in clinical practice. As a result, existing guidelines may not adequately reflect current practice. In the absence of biomarkers to predict the course of disease, methotrexate remains the standard of care initially for most patients with RA. The ability to predict the course of disease could allow more appropriately targeted therapy and higher rates of remission. PMID:19509330

  2. A double blind randomised trial of low power laser treatment in rheumatoid arthritis.

    PubMed Central

    Heussler, J K; Hinchey, G; Margiotta, E; Quinn, R; Butler, P; Martin, J; Sturgess, A D

    1993-01-01

    OBJECTIVES--To define the value of low power laser treatment in small joint rheumatoid arthritis. METHODS--Twenty five women with active disease were recruited. The metacarpophalangeal and proximal interphalangeal joints of one hand were treated with 12 J/cm2 for 30 s with a gallium-aluminium-arsenate laser. The other hand received a sham laser treatment designed so that neither therapist nor patient could distinguish the active laser from the sham laser. Each patient received 12 treatments over four weeks. The following parameters were measured: pain as assessed by visual analogue scale; range of joint movements; grip strength; duration of early morning stiffness, joint circumference, Jebsen's hand assessment; drug usage; total swollen joint counts; Arthritis Impact Measurement Scales; three phase bone scans; haematological and serological tests. RESULTS--A total of 72% of patients reported pain relief but this reduction was reported equally in both hands. No significant changes were seen in other clinical, functional, scintigraphic, or laboratory features. Neither patients nor staff were able to detect which hand was treated with the active laser. CONCLUSION--When this specific laser and dose regimen was used, low power laser treatment had no objective effect on patients with rheumatoid arthritis. It did appear to produce analgesia through a powerful placebo effect. PMID:8257205

  3. HLA-linked rheumatoid arthritis

    SciTech Connect

    Hasstedt, S.J.; Clegg, D.O.; Ingles, L.; Ward, R.H.

    1994-10-01

    Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed in 77 pedigree members including probands; the absence of disease was verified in an additional 261 pedigree members. Pedigree members were serologically typed for HLA. We used likelihood analysis to statistically characterize the HLA-linked RA susceptibility locus. The genetic model assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. In addition, the analysis attributed 78% of the variance within genotypes to genetic or environmental effects shared by siblings. The genetic model inferred in this analysis is consistent with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-fifth of the RA in the population. Although other genes may account for the remaining familial RA, a large portion of RA cases may occur sporadically. 79 refs., 9 tabs.

  4. Rat Bite Fever Resembling Rheumatoid Arthritis.

    PubMed

    Akter, Ripa; Boland, Paul; Daley, Peter; Rahman, Proton; Al Ghanim, Nayef

    2016-01-01

    Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated. PMID:27366177

  5. Rat Bite Fever Resembling Rheumatoid Arthritis

    PubMed Central

    Akter, Ripa; Boland, Paul; Daley, Peter; Rahman, Proton; Al Ghanim, Nayef

    2016-01-01

    Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated. PMID:27366177

  6. 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

  7. The role of autoreactive T cell in the pathogenesis of rheumatoid arthritis and implications for T cell targeted vaccine therapy.

    PubMed

    Wang, D; Li, Y; Liu, Y; Shi, G

    2015-06-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic inflammation of joint synovial tissue and subsequent destruction of associated bone, cartilage and soft tissues. RA is commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs), traditional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids and biologic inhibitors of TNF, IL-1, IL-6, T cells and B cells. The use of these drugs especially biological agents has greatly improved the treatment of RA. Although the pathogenesis of RA remains unclear, T-cell mediated immune response is considered as a critical contributor in RA initiation and progression. It has been hypothesized that arthritogenic T cells (autoreactive T cells) escaping negative selection can recognize arthritogenic antigens and lead to autoimmunity and tissue destruction. Due to the important role of autoreactive T cells in the mechanisms of RA, they might be a novel therapeutic target. Many vaccines targeting autoreactive T cells which can establish immunological self tolerance have been developed. The efficacy of these vaccines has been justified in experimental models of RA and clinical trials. Inhibition of autoreactive T cell response by vaccination might provide a new treatment opinion in RA. PMID:26057192

  8. The occurrence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide: a controlled retrospective follow-up.

    PubMed Central

    Baltus, J A; Boersma, J W; Hartman, A P; Vandenbroucke, J P

    1983-01-01

    In a retrospective follow-up we compared the incidence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide with that in another group of patients with rheumatoid arthritis and also with the incidence of malignancies in the general population. Among 81 patients treated with cyclophosphamide in the past decade 15 malignancies occurred. This was 4.1 times the expected number obtained from a closely matched control group of patients with rheumatoid arthritis not treated with cytotoxic drugs (95% confidence interval 1.5 to 19.0), and 3.7 times the expected number calculated from general population rates (95% confidence interval 2.1 to 5.9). The increase in haematological and lymphoreticular malignancies was specially notable. The data also indicate that the development of malignancies after the start of cyclophosphamide therapy necessitates a certain induction time and that it is to some extent dose-dependent. PMID:6882031

  9. Osteoporosis diagnostics in patients with rheumatoid arthritis

    PubMed Central

    Dura, Marta; Blumfield, Einat; Żuchowski, Paweł; Waszczak, Marzena; Jeka, Sławomir

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease. The development of comorbidities often occurs in the course of RA. One of them is osteoporosis, which has serious social and economic effects and may contribute to the increase in the degree of disability and premature death of the patient. Due to the young age in which RA disease occurs, densitometry (DXA) of the lumbar spine is the basic examination in osteoporosis diagnostics. In the course of RA, much more frequently than in healthy persons of the same age, osteoporotic fractures of vertebral bodies occur, which hinder a correct assessment in the DXA test. Rheumatoid arthritis patients often undergo computed tomography (CT) examination of the abdominal cavity for other medical indications than suspected spinal injury. Then, CT examination may also serve for the assessment of bone density, especially in patients with osteoporotic fractures. PMID:27407274

  10. MICL controls inflammation in rheumatoid arthritis

    PubMed Central

    Redelinghuys, Pierre; Whitehead, Lauren; Augello, Andrea; Drummond, Rebecca A; Levesque, Jean-Michel; Vautier, Simon; Reid, Delyth M; Kerscher, Bernhard; Taylor, Julie A; Nigrovic, Peter A; Wright, John; Murray, Graeme I; Willment, Janet A; Hocking, Lynne J; Fernandes, Maria J G; De Bari, Cosimo; Mcinnes, Iain B; Brown, Gordon D

    2016-01-01

    Background Myeloid inhibitory C-type lectin-like receptor (MICL, Clec12A) is a C-type lectin receptor (CLR) expressed predominantly by myeloid cells. Previous studies have suggested that MICL is involved in controlling inflammation. Objective To determine the role of this CLR in inflammatory pathology using Clec12A−/− mice. Methods Clec12A−/− mice were generated commercially and primarily characterised using the collagen antibody-induced arthritis (CAIA) model. Mechanisms and progress of disease were characterised by clinical scoring, histology, flow cytometry, irradiation bone-marrow chimera generation, administration of blocking antibodies and in vivo imaging. Characterisation of MICL in patients with rheumatoid arthritis (RA) was determined by immunohistochemistry and single nucleotide polymorphism analysis. Anti-MICL antibodies were detected in patient serum by ELISA and dot-blot analysis. Results MICL-deficient animals did not present with pan-immune dysfunction, but exhibited markedly exacerbated inflammation during CAIA, owing to the inappropriate activation of myeloid cells. Polymorphisms of MICL were not associated with disease in patients with RA, but this CLR was the target of autoantibodies in a subset of patients with RA. In wild-type mice the administration of such antibodies recapitulated the Clec12A−/− phenotype. Conclusions MICL plays an essential role in regulating inflammation during arthritis and is an autoantigen in a subset of patients with RA. These data suggest an entirely new mechanism underlying RA pathogenesis, whereby the threshold of myeloid cell activation can be modulated by autoantibodies that bind to cell membrane-expressed inhibitory receptors. PMID:26275430

  11. Serum selenium concentrations in rheumatoid arthritis.

    PubMed Central

    O'Dell, J R; Lemley-Gillespie, S; Palmer, W R; Weaver, A L; Moore, G F; Klassen, L W

    1991-01-01

    Selenium is a trace element and an essential part of the enzyme glutathione peroxidase, which protects cells from oxidative damage. Selenium has been shown to have antiproliferative, anti-inflammatory, antiviral, and immune altering effects. Serum selenium concentrations in 101 patients with seropositive rheumatoid arthritis were found to be significantly lower than those in 29 normal, healthy controls (mean (SD) 148 (42) v 160 (25) micrograms/l) and also lower than those in eight patients with fibrositis (148 (42) v 166 (25) micrograms/l). It is speculated that serum selenium concentrations may modulate the effect of viral or other infections in subjects with the appropriate genetic background and in this way enhance the development or progression of rheumatoid arthritis. PMID:2059080

  12. Nanomedicine delivers promising treatments for rheumatoid arthritis

    PubMed Central

    Prasad, Leena Kumari; O’Mary, Hannah; Cui, Zhengrong

    2015-01-01

    An increased understanding in the pathophysiology of chronic inflammatory diseases, such as rheumatoid arthritis, reveals that the diseased tissue and the increased presence of macrophages and other overexpressed molecules within the tissue can be exploited to enhance the delivery of nanomedicine. Nanomedicine can passively accumulate into chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or be surface conjugated with a ligand to actively bind to receptors overexpressed by cells within chronic inflammatory tissues, leading to increased efficacy and reduced systemic side-effects. This review highlights the research conducted over the past decade on using nanomedicine for potential treatment of rheumatoid arthritis and summarizes some of the major findings and promising opportunities on using nanomedicine to treat this prevalent and chronic disease. PMID:26084368

  13. Parasitic rheumatism presenting as rheumatoid arthritis.

    PubMed

    Burnstein, S L; Liakos, S

    1983-06-01

    A symmetrical polyarthritis with low titer positive rheumatoid factor occurred in a young man who also complained of chronic diarrhea after returning from Vietnam. Endolimax nana grew on stool culture. Both the patient's diarrhea and arthritis responded effectively to therapy with metronidazole. The diagnosis of parasitic rheumatism was made in retrospect. Diagnostic consideration should be given to this entity in patients with unusual arthropathies, particularly if they have stayed in an endemic parasitic country and have gastrointestinal symptoms. PMID:6604161

  14. B Cell Lymphoma mimicking Rheumatoid Arthritis.

    PubMed

    Cosatti, M A; Pisoni, C N; Altuve, J L; Lorente, C

    2016-01-01

    Non Hodking´s lymphoma (NHL) may involve bones but synovial involvement is uncommon. We describe a patient who presented with polyarthritis, sicca symptoms and rash suggestive of rheumatoid arthritis. An atypical skin rash prompted skin and synovial biopsies. A diagnosis of synovial and skin malignant large B-cell lymphoma anaplastic subtype was performed. Chemotherapy with dexamethasone, vincristine and rituximab was started. Following treatment the patient had complete resolution of cutaneous and articular lymphoma manifestations. PMID:27419896

  15. Acquired hemophilia possibly induced by etanercept in a patient with rheumatoid arthritis.

    PubMed

    Banse, Christopher; Benhamou, Ygal; Lequerré, Thierry; Le Cam-Duchez, Véronique; Lévesque, Hervé; Vittecoq, Olivier

    2015-05-01

    A 47-year-old woman with rheumatoid arthritis (RA) treated successively with infliximab, abatacept, and etanercept spontaneously developed subcutaneous bruises and a noncompressive hematoma 11 months after starting etanercept therapy (50mg/week). Her prothrombin time was normal but her activated partial thromboplastin time was increased to 2.48 (normal range, 0.85-1.17). She had a circulating anticoagulant (Rosner index, 45; normal,<13) due to an anti-factor VIII antibody in a titer of 45 Bethesda units. Her factor VIII level was less than 1% (normal range, 55-150). The etanercept and leflunomide were stopped and prednisone was given in a daily dosage of 1mg/kg, in combination with rituximab, two 1-g doses at an interval of 2 weeks. After 5 months, persistence of the anti-factor VIII antibody prompted the initiation of azathioprine therapy, 2mg/kg/d. A remission was achieved 9 months after the diagnosis of acquired hemophilia and was sustained at last follow-up after 3 years. This new case of acquired hemophilia in a patient with RA may reflect a simple association or an inducing role of etanercept. PMID:25617259

  16. A tumour necrosis factor alpha polymorphism is not associated with rheumatoid arthritis.

    PubMed Central

    Wilson, A G; de Vries, N; van de Putte, L B; Duff, G W

    1995-01-01

    OBJECTIVE--To determine whether a polymorphism within the tumour necrosis factor alpha (TNF alpha) gene is associated with susceptibility to, or severity of, rheumatoid arthritis (RA). METHODS--Consecutive patients with recent onset RA were enrolled in a prospective trial. DNA was collected, disease activity was measured at presentation, and radiographic progression at three years was assessed. Typing of TNF alpha was by polymerase chain reaction and single stranded conformation polymorphism analysis. RESULTS--No association of TNF alpha alleles and susceptibility to, or severity of, RA was demonstrated. CONCLUSIONS--These results indicate that this TNF alpha polymorphism does not play a part in the genetic background of RA. PMID:7668906

  17. Lymphomatoid papulosis in a patient treated with adalimumab for juvenile rheumatoid arthritis.

    PubMed

    Park, Ji-Hye; Lee, Jun; Lee, Jae Hyung; Lee, Dong-Youn; Koh, Eun-Mi

    2012-01-01

    Anti-tumor necrosis factor (TNF) agents are now well regarded as highly effective treatment modalities for multiple immunologically mediated diseases, including rheumatoid arthritis, Crohn's disease and psoriasis. The mechanism of action for this particular class of medications involves the blockade of multiple intracellular signaling pathways originating from TNF-α, ultimately inducing a generalized immunosuppressed state. In fact, several cases of lymphomas have been reported in patients treated with anti-TNF-α agents, though it has been difficult to prove any degree of causality. Herein, we described a patient who developed lymphomatoid papulosis after being treated with adalimumab, whereby a clear causality could be established. PMID:23257839

  18. Hepatitis B Virus Reactivation Following Salazosulfapyridine Monotherapy in a Patient with Rheumatoid Arthritis.

    PubMed

    Akashi, Kengo; Saegusa, Jun; Nakamachi, Yuji; Nakazawa, Takashi; Kumagai, Shunichi; Morinobu, Akio

    2016-01-01

    A 72-year-old man was diagnosed with rheumatoid arthritis (RA) and prior hepatitis B virus (HBV) infection. He began treatment with salazosulfapyridine (SASP). Several months later, his blood tests reflected a slightly elevated liver function. Serum tests were positive for hepatitis B surface antigen and HBV-DNA, and the diagnosis of de novo HBV hepatitis was made. A genetic analysis showed that he had polymorphisms of ABCG2 and NAT2, which could lead to high plasma concentrations of SASP and sulfapyridine. To the best of our knowledge, this is the first report of de novo hepatitis developing during SASP monotherapy for RA. PMID:27181550

  19. Delayed diagnosis of Q fever endocarditis in a rheumatoid arthritis patient

    PubMed Central

    Shah, Shailee Y.; Kovacs, Christopher; Tan, Carmela D.; Pettersson, Gosta; Shrestha, Nabin K.; Lutwick, Larry; Gordon, Steven M.

    2015-01-01

    Chronic Q fever caused by Coxiella burnetii is uncommon in the United States and is most often associated with infective endocarditis. We present a 52-year-old woman with a history of aortic valve replacement and rheumatoid arthritis treated with Etanercept with chronic Q fever manifesting as prosthetic valve infective endocarditis. Explanted valve tissue showed organisms confirmed to be C. burnetii by PCR (polymerase chain reaction) sequencing. She subsequently reported consumption of unpasteurized cow milk which was the likely source of C. burnetii. She continues to do well 6 months after valve replacement on oral doxycycline and hydroxychloroquine. PMID:26793469

  20. Pneumocystis jirovecii Pneumonia in a Patient with Rheumatoid Arthritis Treated with Abatacept

    PubMed Central

    Ospina, Fabio E.; Agualimpia, Andrés; Cañas, Carlos A.; Tobón, Gabriel J.

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane inflammation and joint cartilage destruction. Abatacept is a biologic agent that blocks the costimulation signals, preventing antigen presentation and proliferation of T lymphocytes. It is approved for the treatment of patients with RA. Pneumocystis jirovecii pneumonia (PJP) is an infectious disease complicating several immunosuppressive drugs. PJP associated with abatacept has not been reported yet in the medical literature. Various factors, such as the mechanism of action of abatacept, may contribute to predisposing to  Pneumocystis jirovecii infection. In this paper, we report a patient with RA who developed PJP under abatacept treatment. PMID:25313341

  1. Pneumocystis jirovecii Pneumonia in a Patient with Rheumatoid Arthritis Treated with Abatacept.

    PubMed

    Ospina, Fabio E; Agualimpia, Andrés; Bonilla-Abadía, Fabio; Cañas, Carlos A; Tobón, Gabriel J

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane inflammation and joint cartilage destruction. Abatacept is a biologic agent that blocks the costimulation signals, preventing antigen presentation and proliferation of T lymphocytes. It is approved for the treatment of patients with RA. Pneumocystis jirovecii pneumonia (PJP) is an infectious disease complicating several immunosuppressive drugs. PJP associated with abatacept has not been reported yet in the medical literature. Various factors, such as the mechanism of action of abatacept, may contribute to predisposing to  Pneumocystis jirovecii infection. In this paper, we report a patient with RA who developed PJP under abatacept treatment. PMID:25313341

  2. 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

  3. Growth-related gene product {alpha}: A chemotactic cytokine for neutrophils in rheumatoid arthritis

    SciTech Connect

    Koch, A.E.; Pope, R.M. |; Shah, M.R.; Hosaka, S.

    1995-10-01

    Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product {alpha} (gro{alpha}) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro{alpha} (mean 5.3 {+-} 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro{alpha} (mean 4.3 {+-} 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10{sup 5}/cells/ml RPMI 1640/24 h) produced antigenic gro{alpha} (mean 0.2 {+-} 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-{alpha} (mean 1.3 {+-} 0.3 ng/ml) or IL-1{beta} (mean 2.3 {+-} 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro{alpha}: neutrophils (PMNs) (10{sup 7} cells/ml/24 h) produced 3.7 {+-} 0.7 ng/ml. RA SF mononuclear cells produced gro{alpha}, particularly upon incubation with LPS or PHA. Immunoreactive ST gro{alpha} was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro{alpha} for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro{alpha} plays an important role in the ingress of PMNs into the RA joint. 54 refs., 6 figs., 1 tab.

  4. Diffuse alveolar damage in a patient with rheumatoid arthritis under prolonged leflunomide treatment

    PubMed Central

    Keng, Li-Ta; Lin, Mong-Wei; Huang, Hsien-Neng; Chung, Kuei-Pin

    2016-01-01

    Abstract Patients with rheumatoid arthritis (RA) often have pulmonary involvement, and interstitial lung disease (ILD) is the primary manifestation, in which diffuse alveolar damage (DAD) is a rare histopathologic pattern. Leflunomide (LEF) is a frequently prescribed disease-modifying antirheumatic drug for treating RA. LEF-related ILD in the form of DAD has been reported in patients with RA, with the duration of LEF treatment before symptom onset ranging from 6 to 1204 days. We present a case of elderly woman with RA under prolonged LEF treatment for >9 years (3291 days), who had acute respiratory failure with the initial presentation of exertional dyspnea, fever, chills, and productive cough for 2 days. The histopathologic result of surgical lung biopsy was compatible with DAD. She was diagnosed as having LEF-related ILD, based on correlated clinical history, compatible histopathologic examination and excluding possible infection after extensive survey. Although the causative role of LEF cannot be confirmed, this case still hints that LEF-related DAD may occur even if LEF has been prescribed for a prolonged period. PMID:27368035

  5. Establishment of a cell model for screening antibody drugs against rheumatoid arthritis with ADCC and CDC.

    PubMed

    Yan, Li; Hu, Rui; Tu, Song; Cheng, Wen-Jun; Zheng, Qiong; Wang, Jun-Wen; Kan, Wu-Sheng; Ren, Yi-Jun

    2015-01-01

    TNFα played a dominant role in the development and progression of rheumatoid arthritis (RA). Clinical trials proved the efficacies of anti-TNFα agents for curing RA. However, most researchers were concentrating on their abilities of neutralizing TNFα, the potencies of different anti-TNFα agents varied a lot due to the antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). For better understanding and differentiating the potentiality of various candidate anti-TNF reagents at the stage of new drug research and development, present study established a cell model expressing the transmembrane TNFα for usage in in vitro ADCC or CDC assay, meanwhile, the assay protocol described here could provide guidelines for screening macromolecular antibody drugs. A stable cell subline bearing transmembrane TNFα was first established by conventional transfection method, the expression of transmembrane TNFα was approved by flow cytometer, and the performance of the stable subline in ADCC and CDC assay was evaluated, using human peripheral blood mononuclear cells as effector cells, and Adalimumab as the anti-TNFα reagent. The stable cell subline demonstrated high level of surface expression of transmembrane TNFα, and Adalimumab exerted both ADCC and CDC effects on this cell model. In conclusion, the stable cell line we established in present research could be used in ADCC or CDC assay for screening antibody drugs, which would provide in-depth understanding of the potencies of candidate antibody drugs in addition to the traditional TNFα neutralizing assay. PMID:26884918

  6. Development of a framework for reporting health service models for managing rheumatoid arthritis.

    PubMed

    O'Donnell, Siobhan; Li, Linda C; King, Judy; Lauzon, Chantal; Finn, Heather; Vliet Vlieland, Theodora P M

    2010-02-01

    The purpose of this study was to develop a framework for reporting health service models for managing rheumatoid arthritis (RA). We conducted a search of the health sciences literature for primary studies that described interventions which aimed to improve the implementation of health services in adults with RA. Thereafter, a nominal group consensus process was used to synthesize the evidence for the development of the reporting framework. Of the 2,033 citations screened, 68 primary studies were included which described 93 health service models for RA. The origin and meaning of the labels given to these health service delivery models varied widely and, in general, the reporting of their components lacked detail or was absent. The six dimensions underlying the framework for reporting RA health service delivery models are: (1) Why was it founded? (2) Who was involved? (3) What were the roles of those participating? (4) When were the services provided? (5) Where were the services provided/received? (6) How were the services/interventions accessed and implemented, how long was the intervention, how did individuals involved communicate, and how was the model supported/sustained? The proposed framework has the potential to facilitate knowledge exchange among clinicians, researchers, and decision makers in the area of health service delivery. Future work includes the validation of the framework with national and international stakeholders such as clinicians, health care administrators, and health services researchers. PMID:19865842

  7. Ultrasound in Rheumatologic Interstitial Lung Disease: A Case Report of Nonspecific Interstitial Pneumonia in Rheumatoid Arthritis.

    PubMed

    Laria, A; Lurati, A; Scarpellini, M

    2015-01-01

    According to the American Thoracic Society (ATS)/European Respiratory Society consensus classification, idiopathic interstitial pneumonias (IIPs) include several clinic-radiologic-pathologic entities: idiopathic pulmonary fibrosis (IPF), usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. Ultrasound Lung Comets (ULCs) are an echographic chest-sonography hallmark of pulmonary interstitial fibrosis. We describe the ultrasound (US) findings in the follow-up of a NSIP's case in rheumatoid arthritis (RA). PMID:26240772

  8. Sensitivity to non-acetylated salicylates in a patient with asthma, nasal polyps, and rheumatoid arthritis.

    PubMed

    Chudwin, D S; Strub, M; Golden, H E; Frey, C; Richmond, G W; Luskin, A T

    1986-08-01

    A woman experienced exacerbations of bronchial asthma after taking aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis. On oral challenges, she developed an urticarial reaction after tartrazine; urticarial and bronchospastic reactions after salicylsalicylic acid; and urticarial and bronchospastic reactions after choline magnesium trisalicylate. Non-acetylated salicylates have been recommended for use in aspirin- and/or tartrazine-sensitive patients. The results of sensitivity studies of our patient indicates that such patients may also be sensitive to non-acetylated salicylates. PMID:3740556

  9. A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

    PubMed Central

    Vischer, T L

    1988-01-01

    The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

  10. 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. PMID:24517518

  11. Pain Sensitisation in Women with Active Rheumatoid Arthritis: A Comparative Cross-Sectional Study

    PubMed Central

    Vladimirova, Nora; Jespersen, Anders; Bartels, Else Marie; Christensen, Anton W.; Bliddal, Henning; Danneskiold-Samsøe, Bente

    2015-01-01

    Objectives. In some rheumatoid arthritis (RA) patients, joint pain persists without signs of inflammation. This indicates that central pain sensitisation may play a role in the generation of chronic pain in a subgroup of RA. Our aim was to assess the degree of peripheral and central pain sensitisation in women with active RA compared to healthy controls (HC). Methods. 38 women with active RA (DAS28 > 2.6) and 38 female HC were included in, and completed, the study. Exclusion criteria were polyneuropathy, pregnancy, and no Danish language. Cuff Pressure Algometry measurements were carried out on the dominant lower leg. Pain threshold, pain tolerance, and pain sensitivity during tonic painful stimulation were recorded. Results. Women with active RA had significantly lower pain threshold (p < 0.01) and pain tolerance (p < 0.01) than HC. The mean temporal summation- (TS-) index in RA patients was 0.98 (SEM: 0.09) and 0.71 (SEM: 0.04) in HC (p < 0.01). Conclusion. Patients with active RA showed decreased pressure-pain threshold compared to HC. In addition, temporal summation of pressure-pain was increased, indicating central pain sensitization, at least in some patients. Defining this subgroup of patients may be of importance when considering treatment strategies. PMID:26266046

  12. Pain Sensitisation in Women with Active Rheumatoid Arthritis: A Comparative Cross-Sectional Study.

    PubMed

    Vladimirova, Nora; Jespersen, Anders; Bartels, Else Marie; Christensen, Anton W; Bliddal, Henning; Danneskiold-Samsøe, Bente

    2015-01-01

    Objectives. In some rheumatoid arthritis (RA) patients, joint pain persists without signs of inflammation. This indicates that central pain sensitisation may play a role in the generation of chronic pain in a subgroup of RA. Our aim was to assess the degree of peripheral and central pain sensitisation in women with active RA compared to healthy controls (HC). Methods. 38 women with active RA (DAS28 > 2.6) and 38 female HC were included in, and completed, the study. Exclusion criteria were polyneuropathy, pregnancy, and no Danish language. Cuff Pressure Algometry measurements were carried out on the dominant lower leg. Pain threshold, pain tolerance, and pain sensitivity during tonic painful stimulation were recorded. Results. Women with active RA had significantly lower pain threshold (p < 0.01) and pain tolerance (p < 0.01) than HC. The mean temporal summation- (TS-) index in RA patients was 0.98 (SEM: 0.09) and 0.71 (SEM: 0.04) in HC (p < 0.01). Conclusion. Patients with active RA showed decreased pressure-pain threshold compared to HC. In addition, temporal summation of pressure-pain was increased, indicating central pain sensitization, at least in some patients. Defining this subgroup of patients may be of importance when considering treatment strategies. PMID:26266046

  13. Rheumatoid arthritis as a hyper-endoplasmic-reticulum-associated degradation disease.

    PubMed

    Yamasaki, Satoshi; Yagishita, Naoko; Tsuchimochi, Kaneyuki; Nishioka, Kusuki; Nakajima, Toshihiro

    2005-01-01

    We introduce Synoviolin as a novel pathogenic factor in rheumatoid arthritis (RA). Experimental studies indicate that this endoplasmic reticulum (ER)-resident E3 ubiquitin ligase has important functions in the ER-associated degradation (ERAD) system, an essential system for ER homeostasis. Overexpression of Synoviolin in mice causes arthropathy with synovial hyperplasia, whereas heterozygous knockdown results in increased apoptosis of synovial cells and resistance to collagen-induced arthritis in mice. On the basis of these experimental data, we propose that excess elimination of unfolded proteins (that is, 'hyper-ERAD') by overexpression of Synoviolin triggers synovial cell overgrowth and hence a worsening of RA. Further analysis of the hyper-ERAD system may permit the complex pathomechanisms of RA to be uncovered. PMID:16207344

  14. Indirect costs of rheumatoid arthritis

    PubMed Central

    Raciborski, Filip; Kwiatkowska, Brygida

    2015-01-01

    It is estimated that in Poland about 400,000 persons in general suffer from inflammatory joint diseases, including rheumatoid arthritis (RA). Epidemiological surveys documenting the frequency and disturbance of musculoskeletal disorders in the Polish population are few in number. Most of the estimations are based on epidemiological data from other countries (prevalence of 0.5–1%). According to the data of the National Health Fund in Poland 135,000–157,000 persons in total are treated because of rheumatoid arthritis per year [ICD10 (International Statistical Classification of Diseases and Related Health Problems): M05, M06]. In the case of this group of diseases indirect costs significantly outweigh the direct costs. Indirect costs increase together with activity level of the disease. The cost analysis of productivity loss of RA patients indicates that sickness absenteeism and informal care are the most burdensome. At the national level it amounts in total from 1.2 billion to 2.8 billion PLN per year, depending on the method of analysis. These costs could be significantly reduced through early diagnosis and introduction of effective treatment. PMID:27407258

  15. Quercetin: a potential natural drug for adjuvant treatment of rheumatoid arthritis.

    PubMed

    Ji, Jian-Jun; Lin, Yuan; Huang, Shan-Shan; Zhang, Hou-Li; Diao, Yun-Peng; Li, Kun

    2013-01-01

    Rheumatoid arthritis (RA) is the rheumatism mainly manifested as disabling joint disease and mainly involves hands, wrists, feet and other small joints. Recurrent arthritis attacks, synovial cell hypertrophy and hyperplasia and bone and cartilage damages eventually lead to joint dysfunction and other complications, and there is no cure. Quercetin (QU) is a kind of natural flavonoids, with lipid-lowering, anti-inflammatory and other pharmacological activities, and minor toxic side effects. Thus, we assume that QU may be an adjuvant natural drug for treatment of RA. The possible mechanism is through regulation of NF-κB, to inhibit the transcription of joint synovitis factors, hinder the generation of inflammatory factors, and inhibit the inflammatory reaction; through inhibiting the activities of VEGF, bFGF, MMP-2 and other cytokines, to inhibit angiogenesis in multiple links and inhibit synovial pannus formation. QU may be an adjuvant natural drug for treatment of RA. PMID:24146468

  16. Efficacy and safety of a non-acetylated salicylate, choline magnesium trisalicylate, in the treatment of rheumatoid arthritis.

    PubMed

    Rothwell, K G

    1983-01-01

    The results of three double-blind, multicentre trials are reviewed to compare the efficacy of acetysalicylic acid (ASA) and a non-acetylated salicylate, choline magnesium trisalicylate (CMT), in the treatment of rheumatoid arthritis. In each trial, patients were randomly assigned to receive comparable doses of salicylate as either ASA or CMT. Mean values for clinical indicators of rheumatoid arthritis (number of painful joints, articular index, number of swollen joints, swelling index, duration of morning stiffness) showed similar or greater improvement among groups of patients receiving CMT, compared to those receiving ASA. In addition, the incidence of gastro-intestinal side-effects was lower among patients receiving CMT. PMID:6360749

  17. Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis

    PubMed Central

    Greven, D E A; Cohen, E S; Gerlag, D M; Campbell, J; Woods, J; Davis, N; van Nieuwenhuijze, A; Lewis, A; Heasmen, S; McCourt, M; Corkill, D; Dodd, A; Elvin, J; Statache, G; Wicks, I P; Anderson, I K; Nash, A; Sleeman, M A; Tak, P P

    2015-01-01

    Objective Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)–GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue and investigated the effects of anti-GM-CSFRα antibody treatment in vitro and in vivo in a preclinical model of RA. Methods We compared GM-CSFRα expression on macrophages positive for CD68 or CD163 on synovial biopsy samples from patients with RA or psoriatic arthritis (PsA) to disease controls. In addition, we studied the effects of CAM-3003, an anti-GM-CSFR antibody in a collagen induced arthritis model of RA in DBA/1 mice. The pharmacokinetic profile of CAM-3003 was studied in naïve CD1(ICR) mice (see online supplement) and used to interpret the results of the pharmacodynamic studies in BALB/c mice. Results GM-CSFRα was expressed by CD68 positive and CD163 positive macrophages in the synovium, and there was a significant increase in GM-CSFRα positive cells in patients in patients with RA as well as patients with PsA compared with patients with osteoarthritis and healthy controls. In the collagen induced arthritis model there was a dose dependent reduction of clinical arthritis scores and the number of F4/80 positive macrophages in the inflamed synovium after CAM-3003 treatment. In BALB/c mice CAM-3003 inhibited recombinant GM-CSF mediated margination of peripheral blood monocytes and neutrophils. Conclusions The findings support the ongoing development of therapies aimed at interfering with GM-CSF or its receptor in various forms of arthritis, such as RA and PsA. PMID:24936585

  18. Role of self-esteem and autonomy in determining medication compliance among adolescents with juvenile rheumatoid arthritis.

    PubMed

    Litt, I F; Cuskey, W R; Rosenberg, A

    1982-01-01

    This study was designed to improve understanding of adolescents' compliance with medical regimens. Compliance with salicylate therapy among adolescents with juvenile rheumatoid arthritis was examined in relationship to two of the most important issues of adolescent psychosocial development--self-image and autonomy. Standardized instruments that assessed these variables were administered to 38 adolescents with juvenile rheumatoid arthritis during the year in which compliance was determined, utilizing serum salicylate measurements. Patients and disease-related characteristics were also recorded, and interactions with personality variables were examined. The data show that adolescents with juvenile rheumatoid arthritis who comply with their medical regimen are those who have high self-esteem and are allowed more autonomy than the noncompliers. The longer the duration of the illness and the more symptoms present at onset, the poorer was self-concept, and hence compliance, at adolescence. PMID:7054755

  19. Future therapies for rheumatoid arthritis: remedies from the horns of a dilemma?

    PubMed

    Staite, N D

    1997-07-01

    Drugs used to treat arthritis can be broadly classified into either anti-inflammatory or immunosuppressive/immunomodulatory agents. Non-steroidal anti-inflammatory drugs (NSAIDs) are used for both osteoarthritis (OA) and rheumatoid arthritis (RA), while drugs with an immunological mechanism of action are only applicable to RA. The total market value for anti-arthritic drugs is estimated to be 8.4 bn dollars, with the OA segment worth 6.9 bn dollars. In contrast, the major RA markets are valued at approximately 1.5 bn dollars. Drugs currently in late phase development reflect the accepted approaches towards treating the symptoms of arthritis, or suppressing immunological mechanisms considered to be the driving force for the underlying disease process in RA. The size of both the RA and OA markets, however, creates an incentive to develop new therapeutics which do not conform to these two approaches, but target new molecular mechanisms. Compounds currently in preclinical development demonstrate that it may be possible to combine anti-inflammatory and slow-acting antirheumatic activity into a single therapeutic. This new generation of anti-arthritic compounds has the potential to redefine the way in which common forms of arthritis, mixed connective tissue diseases and musculoskeletal diseases are treated in the future. PMID:15989642

  20. Cervical myelopathy in rheumatoid arthritis.

    PubMed

    Meijers, K A; Cats, A; Kremer, H P; Luyendijk, W; Onvlee, G J; Thomeer, R T

    1984-01-01

    Results obtained in 43 Rheumatoid arthritis (RA) patients with cervical myelopathy are described; all patients showed several alarm signs together with neurological disturbances. Thirty-four cases were operable; nine patients were not operated upon for various reasons (refusal, and general condition). In the surgically treated patients, the changes were localized in the C1-C2 area (n = 20), in the area below C2 (n = 5), or in both (n = 9). The patients were put on skull traction pre- and post-operatively and nursed on a circo-electric bed. Pre-operatively, the duration of traction varied from a few days to weeks (mean 3 weeks). Post-operatively, the patients were given continuous skull traction for 2 1/2-3 months. This procedure yielded neurological improvement and a stable graft in all but two patients. On follow-up, recurrence of neurological complaints was seen in nine patients, in four due to a new slip at a lower level. Three of these cases were reoperated with good results. Twenty-three patients have died: four 'early' (one pre-operatively and three within 6 weeks post-operatively) and 19 'late'. The mean duration of follow-up was 4.5 years. In those who died 'late', the cause of death was due to the effects of an unstable graft in two cases and in the others the causes were not related to changes in the cervical spine. In the 10 patients who are still alive the mean duration of follow-up is 5 years. The nine patients who were not operated upon all died within a year, 4 of them due to consequences of cord compression. If cervical spondylodesis is feasible in an RA patient with myelopathy, the procedure is advocated. PMID:6529877

  1. A historical perspective concerning population-based and clinical studies of early arthritis and early rheumatoid arthritis.

    PubMed

    Sokka, T; Pincus, T

    2003-01-01

    Research concerning early arthritis and early rheumatoid arthritis (RA) may be considered to have begun with population-based studies in the United Kingdom, the United States and Scandinavia, from the late 1950s to the late 1960s. These studies indicated that the majority of people with clinical findings of RA had no evidence of disease 3-5 years later, and that only about 25% to 30% of people in a population who met the criteria for RA had rheumatoid factor. These findings may have contributed to an underestimation of RA until the severity of long-term outcomes of clinical RA were recognized in the 1980s on the basis of clinical cohorts. The first major early RA clinical cohort was established in 1957-1963 in Bath, England. Although results at 3 and even 11 years were not overly unfavorable, by 15 and 20 years most patients had severe outcomes of functional declines and premature mortality. The Middle-sex (UK) early RA cohort established in 1966-1971 indicated that radiographic abnormalities were observed in about 70% of patients by 2 years of disease, and were seen in most patients initially in the feet. The Memphis (Tennessee, USA) early RA cohort established in 1967-1971 suggested that a progressive course of RA is predicted by a higher number of involved joints at baseline. The Lund (Sweden) early RA cohort established in 1985-1989 indicated rather severe long-term outcomes in patients treated according to traditional conservative approaches to use of disease modifying anti-rheumatic drugs (DMARDs). The early RA study (ERAS) involving nine National Health Service trusts in the UK was established in 1987-93, and showed associations of education level and socioeconomic status with clinical status. The movement towards early arthritis clinics was given great impetus following the work by Emery in the early 1990s. These studies and others described elsewhere in this supplement have contributed to the foundations for the clinical approach to early arthritis in the

  2. Imaging in early rheumatoid arthritis.

    PubMed

    McQueen, Fiona M

    2013-08-01

    Imaging in early rheumatoid arthritis (RA) has undergone extraordinary change in recent years and new techniques are now available to help the clinician diagnose and manage patients much more effectively than previously. While established modalities such as plain radiography (X-Ray) remain important, especially for detection of erosions and determining the progression of joint damage, there are many instances where ultrasound (US), magnetic resonance imaging (MRI) and computed tomography (CT) scanning provide added information. MRI and US are now used regularly by clinicians to help diagnose RA in the pre-radiographic stage as they offer improved visualisation of joint erosions. They also have the potential to provide prognostic information as MRI bone oedema/osteitis is linked to the later development of erosions and power Doppler ultrasound (PDUS) joint positivity is also a predictor of joint damage. Nuclear imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) are also highly sensitive for detecting joint change in early RA and pre-RA but not yet used clinically mainly because of accessibility and radiation exposure. MRI, US, scintigraphy, SPECT and PET have all been shown to detect sub-clinical joint inflammation in patients in clinical remission, a state that is now the goal of most treat-to-target management strategies. Thus, imaging may be used to direct therapeutic decision making and MRI is also now being used in clinical trials to determine the impact of disease-suppressing therapy on the course of synovitis and osteitis. As is the case for all tests, it would be unwise to rely completely on any one imaging result, as false positives and negatives can occur for all modalities. Thus, the clinician needs to choose the most relevant and reliable imaging test, while also striving to minimise patient discomfort, radiation burden and economic impact. PMID:24315051

  3. The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis

    PubMed Central

    Brown, Keith D; Claudio, Estefania; Siebenlist, Ulrich

    2008-01-01

    Nuclear factor-κB (NF-κB) is an inducible transcription factor controlled by two principal signaling cascades, each activated by a set of signal ligands: the classical/canonical NF-κB activation pathway and the alternative/noncanonical pathway. The former pathway proceeds via phosphorylation and degradation of inhibitor of NF-κB (IκB) and leads most commonly to activation of the heterodimer RelA/NF-κB1(p50). The latter pathway proceeds via phosphorylation and proteolytic processing of NF-κB2 (p100) and leads to activation, most commonly, of the heterodimer RelB/NF-κB2 (p52). Both pathways play critical roles at multiple levels of the immune system in both health and disease, including the autoimmune inflammatory response. These roles include cell cycle progression, cell survival, adhesion, and inhibition of apoptosis. NF-κB is constitutively activated in many autoimmune diseases, including diabetes type 1, systemic lupus erythematosus, and rheumatoid arthritis (RA). In this review we survey recent developments in the involvement of the classical and alternative pathways of NF-κB activation in autoimmunity, focusing particularly on RA. We discuss the involvement of NF-κB in self-reactive T and B lymphocyte development, survival and proliferation, and the maintenance of chronic inflammation due to cytokines such as tumor necrosis factor-α, IL-1, IL-6, and IL-8. We discuss the roles played by IL-17 and T-helper-17 cells in the inflammatory process; in the activation, maturation, and proliferation of RA fibroblast-like synovial cells; and differentiation and activation of osteoclast bone-resorbing activity. The prospects of therapeutic intervention to block activation of the NF-κB signaling pathways in RA are also discussed. PMID:18771589

  4. Randomized clinical trials as reflexive-interpretative process in patients with rheumatoid arthritis: a qualitative study.

    PubMed

    de Jorge, Mercedes; Parra, Sonia; de la Torre-Aboki, Jenny; Herrero-Beaumont, Gabriel

    2015-08-01

    Patients in randomized clinical trials have to adapt themselves to a restricted language to capture the necessary information to determine the safety and efficacy of a new treatment. The aim of this study was to explore the experience of patients with rheumatoid arthritis after completing their participation in a biologic therapy randomized clinical trial for a period of 3 years. A qualitative approach was used. The information was collected using 15 semi-structured interviews of patients with rheumatoid arthritis. Data collection was guided by the emergent analysis until no more relevant variations in the categories were found. The data were analysed using the grounded theory method. The objective of the patients when entering the study was to improve their quality of life by initiating the treatment. However, the experience changed the significance of the illness as they acquired skills and practical knowledge related to the management of their disease. The category "Interactional Empowerment" emerged as core category, as it represented the participative experience in a clinical trial. The process integrates the follow categories: "weight of systematisation", "working together", and the significance of the experience: "the duties". Simultaneously these categories evolved. The clinical trial monitoring activities enabled patients to engage in a reflexive-interpretative mechanism that transformed the emotional and symbolic significance of their disease and improved the empowerment of the patient. A better communicative strategy with the health professionals, the relatives of the patients, and the community was also achieved. PMID:25636236

  5. Pain mystery score beliefs: a comparison of fibromyalgia and rheumatoid arthritis.

    PubMed

    Ferrari, Robert; Russell, Anthony Science

    2014-01-01

    Objectives. To compare the mysteriousness scores of the Pain Beliefs and Perceptions Inventory in fibromyalgia. Methods. Two cohorts of patients, one with fibromyalgia (FM) and one with rheumatoid arthritis (RA), completed the Mystery Scale component of the Pain Beliefs and Perceptions Inventory to determine whether subjects in the two diagnostic groups had significantly different scores on the Mystery Scale. Results. A total of 126 subjects (64 FM, 62 RA) completed all questionnaires. The FM group had a greater percentage of female subjects, more severe pain, more severe anxiety, more severe depression, and a higher perceived injustice score. When the RA and FM group scores for the Mystery Scale were adjusted for age, sex, pain severity, HADS scores, and perceived injustice scores, the FM group still had a higher Mystery Scale score. Discussion. Fibromyalgia is associated with a higher level of perception of mysteriousness in the Pain Beliefs and Perceptions Inventory than is seen with rheumatoid arthritis. This difference appears to be independent of levels of pain, depression, anxiety, and perceived injustice. This sense of mysteriousness may reflect a lack of understanding of pain in fibromyalgia as previously reported and may be an area to be addressed in therapy. PMID:25548570

  6. A controlled trial of nandrolone decanoate in the treatment of rheumatoid arthritis in postmenopausal women.

    PubMed Central

    Bird, H A; Burkinshaw, L; Pearson, D; Atkinson, P J; Leatham, P A; Hill, J; Raven, A; Wright, V

    1987-01-01

    To determine whether an anabolic steroid had any benefit in the treatment of rheumatoid arthritis 47 patients entered a parallel group study. Twenty four received nandrolone decanoate 50 mg intramuscularly every third week for two years and 23 patients received no anabolic steroids. Other therapy was unaltered. Patients attended for clinical and biochemical assessments as well as the objective assessments of elementary body composition by in vivo neutron activation analysis and measurement of the mineral content of the distal femur by single photon absorptiometry on five occasions. A modest clinical deterioration (except for grip strength) was seen in both groups. No significant changes in calcium or alkaline phosphatase were seen. There was no significant change in total body calcium, total body phosphorus, body weight, or bone index/bone width measurements in either group. Significant increases occurred in total body nitrogen, total body potassium, haemoglobin, and packed cell volume (by six months) in the group treated with nandrolone decanoate. Comparison of 10 patients in the group treated with nandrolone decanoate also receiving oral steroid therapy with 14 patients in this group not receiving oral steroid therapy showed no significant differences. The main side effect of nandrolone decanoate was hoarseness. No radiological changes were seen. Nandrolone decanoate, in a dose that produces a significant anabolic effect, has no demonstrable action on bone metabolism in rheumatoid arthritis but may improve the chronic anaemia by six months. PMID:3555359

  7. A radiographic evaluation of temporomandibular and hand (Metacarpophalangeal) / wrist joints of patients with adult rheumatoid arthritis

    PubMed Central

    Kurup, Seema; Gharote, Harshkant; Jose, Renju

    2012-01-01

    Background: A review of literature revealed that, although the involvement of temporomandibular joint (TMJ) in rheumatoid arthritis (RA) patients is not uncommon, variation in presentation persist. Comparative studies of bony changes in the right and left TMJ with the right and left peripheral hand (Metacarpophalangeal-MCP)/wrist joints have not been done, to the best of our knowledge. Materials and Methods: In this cross-sectional study, the temporomandibular and hand (MCP) and wrist joints of fifteen rheumatoid arthritis patients were evaluated with questionnaires, clinical and lab assessment and radiographically using conventional radiographs and computed tomography. Students t-test was applied for the statistical analysis of the data obtained and a P value of 0.05 was considered as statistically significant. Results: Comparisons between the right TMJ with right MCP/wrist joint and left TMJ with left MCP/wrist joint did not reveal statistically significant results. Radiographically, flattening and erosions were the common manifestations. MCP joints were more affected than the wrist, but whenever the wrist was involved, it was more likely to be bilaterally affected. Conclusions: Although the TMJ showed osseous changes of a higher grade than the hand (MCP) and wrist joints radiographically, it was observed that patients were more aware of the peripheral joint discomfort. There were no significant differences between TMJ and peripheral joints on both right and left sides. PMID:23814559

  8. The Role of Power Doppler Ultrasonography as Disease Activity Marker in Rheumatoid Arthritis

    PubMed Central

    Bhasin, Shaloo; Cheung, Peter P.

    2015-01-01

    Structural damage in rheumatoid arthritis (RA) occurs early if inflammation is not treated promptly. Treatment targeted to reduce inflammation, in particular, that of synovial inflammation in the joints (synovitis), has been recommended as standard treat-to-target recommendations by rheumatologists. The goal is to achieve disease remission (i.e., no disease activity). Several accepted remission criteria have not always equated to the complete absence of true inflammation. Over the last decade, musculoskeletal ultrasonography has been demonstrated to detect subclinical synovitis not appreciated by routine clinical or laboratory assessments, with the Power Doppler modality allowing clinicians to more readily appreciate true inflammation. Thus, targeting therapy to Power Doppler activity may provide superior outcomes compared with treating to clinical targets alone, making it an attractive marker of disease activity in RA. However, more validation on its true benefits such as its benefits to patients in regard to patient related outcomes and issues with standardized training in acquisition and interpretation of power Doppler findings are required. PMID:26063952

  9. 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)

  10. Termination of disease-modifying antirheumatic drugs in rheumatoid arthritis and in psoriatic arthritis. A comparative study of 270 cases.

    PubMed

    Ujfalussy, I; Koó, E; Seszták, M; Gergely, P

    2003-04-01

    102 rheumatoid arthritis (RA) and 104 psoriatic arthritis (PsA) patients' records were analysed according to a standardised protocol. Using Cox regression, life-table analysis and log rank test, the effectiveness and toxicity of, and duration of disease modifying antirheumatic drug (DMARD) treatment were compared in RA and PsA. RA patients were treated with gold sodium thiomalate (GST), methotrexate (MTX) and sulphasalazine (SSZ) for a median duration of 35, 72 and 12 months respectively, whereas PsA patients were treated for 12, 12 and 17 months. The differences for GST and MTX were statistically significant (p=0.0043 and 0.0447). Drug toxicity was more frequently seen among patients with PsA (p=0.0023). No difference in efficacy could be proved. Results suggest that there is a significant difference between RA and PsA patients in terms of toxicity of these agents. Therefore, separate treatment strategies are needed, and earlier results with RA may not be directly applicable to PsA. PMID:12721703

  11. 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

  12. Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies.

    PubMed

    Boers, M; Croonen, A M; Dijkmans, B A; Breedveld, F C; Eulderink, F; Cats, A; Weening, J J

    1987-09-01

    Renal abnormalities in 132 necropsied patients with rheumatoid arthritis were studied. Clinical findings before death included extra-articular manifestations of the disease (86% of patients), systemic vasculitis (6%), and uraemia (23%). Necropsy findings included nephrosclerosis (90%), systemic vasculitis (14%) with kidney involvement in 8%, amyloidosis (11%), membranous glomerulopathy (8%), and focal glomerular disease (8%). Association with clinical data suggests that both rheumatoid and non-rheumatoid disease may play a part in the cause of these abnormalities. PMID:3675007

  13. A 21-year-old man with systemic-onset juvenile rheumatoid arthritis, cough and progressive dyspnea.

    PubMed

    Leber, A; Carette, S; Chapman, K R; Hwang, D M; Singer, L G; Marras, T K

    2010-01-01

    Primary or nonobstructive, endogenous lipoid pneumonia is a rare clinical entity usually associated with an underlying systemic disease. The present report describes a case involving a 21-year-old man with systemic-onset juvenile rheumatoid arthritis who developed primary endogenous lipoid pneumonia. Multiple treatment regimens were attempted; however, definitive management was only achieved through double-lung transplantation. PMID:20617213

  14. MicroRNAs in rheumatoid arthritis.

    PubMed

    Salehi, Eisa; Eftekhari, Rahil; Oraei, Mona; Gharib, Alvand; Bidad, Katayoon

    2015-04-01

    The role of genetic and epigenetic factors in the development of rheumatic diseases has been an interesting field of research over the past decades all around the world. Research on the role of microRNAs (miRNAs) in rheumatoid arthritis (RA) has been active and ongoing, and investigations have attempted to use miRNAs as biomarkers in disease diagnosis, prognosis, and treatment. This review focuses on experimental researches in the field of miRNAs and RA to present the data available up to this date and includes researches searched by keywords "microRNA" and "rheumatoid arthritis" in PubMed from 2008 to January 2015. All references were also searched for related papers. miRNAs are shown to act as proinflammatory or anti-inflammatory agents in diverse cell types, and their role seems to be regulatory in most instances. Researchers have evaluated miRNAs in patients compared to controls or have investigated their role by overexpressing or silencing them. Multiple targets have been identified in vivo, in vitro, or in silico, and the researches still continue to show their efficacy in clinical settings. PMID:25736037

  15. Surgical Management of the Forefoot in Patients with Rheumatoid Arthritis - A Review Article

    PubMed Central

    Nash, W.J.; Al-Nammari, S.; Khan, W.S.; Pengas, I.P.

    2015-01-01

    Foot and ankle pathologies cause a significant disease burden on rheumatoid patients. Forefoot pathologies causes pain, callosities and possibly ulceration, and can cause problems with footwear. Forefoot correction in rheumatoid patients has historically comprised of excision of diseased joints. While satisfaction was high with this procedure, complications, changing expectations and improvement in medical therapy have raised expectation of patients, physicians and surgeons alike. This review assesses the role of joint preserving osteotomies and arthrodesis, as well as associated complications. It also describes the role of the multidisciplinary team in the management of these patients. PMID:25861409

  16. Investigating the Value of Abatacept in the Treatment of Rheumatoid Arthritis: A Systematic Review of Cost-Effectiveness Studies

    PubMed Central

    Petrakis, Ioannis; Kyriopoulos, John

    2013-01-01

    Background. Rheumatoid arthritis is a progressive inflammatory disease that affects greatly patients' quality of life and demands for aggressive management early on during the course of the disease. The discovery of biologics has equipped rheumatologists with evolutionary treatment tools but has also impacted greatly management costs. Objectives. To conduct a systematic review in order to evaluate the cost effectiveness of abatacept in the treatment of moderate to severe rheumatoid arthritis. Methods. Pubmed, the International Society for Pharmacoeconomics and Outcomes Research Outcomes Research Digest, the National Health System Economic Evaluation Database, and the Database of Abstracts of Reviews of Effects were searched. Results. In total 301 studies were identified and 42 met the inclusion criteria. Half of the selected studies evaluated abatacept in the treatment of rheumatoid arthritis, after failure of or intolerance to tumor necrosis factor alpha inhibitors. Of those, 82% were in favor of abatacept as a cost-effective or dominant strategy versus varying alternatives, whereas 18% favored other treatments. Conclusion. The majority of evidence from the published literature supports that abatacept can be a cost-effective alternative in the treatment of moderate to severe rheumatoid arthritis, especially in patients that have demonstrated inadequate response or intolerance to anti-TNF agents or conventional disease modifying antirheumatic drugs. PMID:23819062

  17. Home Care Guide on Juvenile Rheumatoid Arthritis (For Parents).

    ERIC Educational Resources Information Center

    Giesecke, Linda L.; And Others

    The booklet, written by the medical staff of a children's hospital, provides information for parents of children with juvenile rheumatoid arthritis (JRA). Arthritis is a swelling of the joint(s) in children and lasts for over 6 weeks (sometimes many years). Aspirin is the main medicine given for JRA, and it works not only to control pain but also,…

  18. Biological Basis for the Use of Botanicals in Osteoarthritis and Rheumatoid Arthritis: A Review

    PubMed Central

    2005-01-01

    Osteoarthritis (OA) of the knee and hip is a debilitating disease affecting more women than men and the risk of developing OA increases precipitously with aging. Rheumatoid arthritis (RA), the most common form of inflammatory joint diseases, is a disease of unknown etiology and affects ∼1% of the population worldwide, and unlike OA, generally involves many joints because of the systemic nature of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first drugs of choice for the symptomatic treatment of both OA and RA. Because of the risks associated with the use of NSAIDs and other limitations, the use of alternative therapies, such as acupuncture and medicinal herbs, is on the rise and according to reports ∼60–90% of dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine (CAM). This paper reviews the efficacy of some of the common herbs that have a history of human use and their anti-inflammatory or antiarthritic properties have been evaluated in animal models of inflammatory arthritis, in studies employing well defined and widely accepted in vitro models that use human chondrocytes/cartilage explants or in clinical trials. Available data suggests that the extracts of most of these herbs or compounds derived from them may provide a safe and effective adjunctive therapeutic approach for the treatment of OA and RA. This, in turn, argues for trials to establish efficacy and optimum dosage of these compounds for treating human inflammatory and degenerative joint diseases. PMID:16136208

  19. Anglo-French contributions to the recognition of rheumatoid arthritis

    PubMed Central

    Fraser, Kevin J.

    1982-01-01

    Early descriptions of rheumatoid arthritis in the English and French literature are reviewed. Charcot pointed out that the disease was recognised as distinct from gout in eighteenth century England, and pictorial evidence for this is presented. His own work on arthritis led to a series of noteworthy interactions with Alfred Baring Garrod, which are discussed. Images PMID:7051988

  20. The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in rheumatoid arthritis.

    PubMed

    Fishman, Pnina; Cohen, Shira

    2016-09-01

    The Gi protein-associated A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells, and this high expression is also reflected in the peripheral blood mononuclear cells of patients with autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. CF101, a selective agonist with high affinity to the A3AR, is known to induce robust anti-inflammatory effect in experimental animal models of adjuvant-, collagen-, and tropomyosin-induced arthritis. The effect is mediated via a definitive molecular mechanism entailing deregulation of the nuclear factor-κB (NF-κB) and the Wnt signal transduction pathways resulting in apoptosis of inflammatory cells. CF101 was found to be safe and well tolerated in all preclinical, phase I, and phase II human clinical studies. In two phase II clinical studies where CF101 was administered to rheumatoid arthritis (RA) patients as a stand-alone drug, a significant anti-rheumatic effect and a direct significant correlation were found between receptor expression at baseline and patients' response to the drug, suggesting that A3AR may be utilized as a predictive biomarker. The A3AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients' response to CF101. This is a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population. PMID:26886128

  1. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis

    PubMed Central

    Kotake, Shigeru; Udagawa, Nobuyuki; Takahashi, Naoyuki; Matsuzaki, Kenichiro; Itoh, Kanami; Ishiyama, Shigeru; Saito, Seiji; Inoue, Kazuhiko; Kamatani, Naoyuki; Gillespie, Matthew T.; Martin, T. John; Suda, Tatsuo

    1999-01-01

    IL-17 is a newly discovered T cell–derived cytokine whose role in osteoclast development has not been fully elucidated. Treatment of cocultures of mouse hemopoietic cells and primary osteoblasts with recombinant human IL-17 induced the formation of multinucleated cells, which satisfied major criteria of osteoclasts, including tartrate-resistant acid phosphatase activity, calcitonin receptors, and pit formation on dentine slices. Direct interaction between osteoclast progenitors and osteoblasts was required for IL-17–induced osteoclastogenesis, which was completely inhibited by adding indomethacin or NS398, a selective inhibitor of cyclooxgenase-2 (COX-2). Adding IL-17 increased prostaglandin E2 (PGE2) synthesis in cocultures of bone marrow cells and osteoblasts and in single cultures of osteoblasts, but not in single cultures of bone marrow cells. In addition, IL-17 dose-dependently induced expression of osteoclast differentiation factor (ODF) mRNA in osteoblasts. ODF is a membrane-associated protein that transduces an essential signal(s) to osteoclast progenitors for differentiation into osteoclasts. Osteoclastogenesis inhibitory factor (OCIF), a decoy receptor of ODF, completely inhibited IL-17–induced osteoclast differentiation in the cocultures. Levels of IL-17 in synovial fluids were significantly higher in rheumatoid arthritis (RA) patients than osteoarthritis (OA) patients. Anti–IL-17 antibody significantly inhibited osteoclast formation induced by culture media of RA synovial tissues. These findings suggest that IL-17 first acts on osteoblasts, which stimulates both COX-2–dependent PGE2 synthesis and ODF gene expression, which in turn induce differentiation of osteoclast progenitors into mature osteoclasts, and that IL-17 is a crucial cytokine for osteoclastic bone resorption in RA patients. PMID:10225978

  2. Sarilumab for the treatment of rheumatoid arthritis.

    PubMed

    Cooper, Simon

    2016-03-01

    Simon Cooper is interviewed by Ellen Clarke, Commissioning Editor Simon Cooper has >18 years of global experience in the pharmaceutical industry. He joined Sanofi in July 2014 as the Vice President, Global Project Head. In his current position at Sanofi, Dr Cooper is responsible for the clinical development of sarilumab and the worldwide submission in rheumatoid arthritis. He joined Sanofi after serving as the Global Program Medical Director at Novartis since 2012. In this role, Dr Cooper acted as the clinical lead for secukinumab psoriasis submission. Prior to Novartis, Dr Cooper held various posts at Human Genome Sciences, USA, including Executive Director of Clinical Research, Senior Director of Clinical Research and Director of Clinical Research. During his tenure at Human Genome Sciences, USA, Dr Cooper was involved in the submission of belimumab leading to its approval for SLE, and was responsible for its subsequent clinical development program. Dr Cooper has also previously held positions at MedImmune Ltd, UK, Roche, Napp Pharmaceutical Research Ltd, Wyeth Research and Medeval Ltd. In these roles, his responsibilities ranged from medical oversight of clinical trials to medical support for commercial, medical affairs and business development. He received a Bachelor of Medicine and Bachelor of Surgery from University of Newcastle upon Tyne Medical School. PMID:26860742

  3. The Effects of Aromatherapy Massage and Reflexology on Pain and Fatigue in Patients with Rheumatoid Arthritis: A Randomized Controlled Trial.

    PubMed

    Gok Metin, Zehra; Ozdemir, Leyla

    2016-04-01

    Nonpharmacologic interventions for symptom management in patients with rheumatoid arthritis are underinvestigated. Limited data suggest that aromatherapy massage and reflexology may help to reduce pain and fatigue in patients with rheumatoid arthritis. The aim of this study was to examine and compare the effects of aromatherapy massage and reflexology on pain and fatigue in patients with rheumatoid arthritis. The study sample was randomly assigned to either an aromatherapy massage (n = 17), reflexology (n = 17) or the control group (n = 17). Aromatherapy massage was applied to both knees of subjects in the first intervention group for 30 minutes. Reflexology was administered to both feet of subjects in the second intervention group for 40 minutes during weekly home visits. Control group subjects received no intervention. Fifty-one subjects with rheumatoid arthritis were recruited from a university hospital rheumatology clinic in Turkey between July 2014 and January 2015 for this randomized controlled trial. Data were collected by personal information form, DAS28 index, Visual Analog Scale and Fatigue Severity Scale. Pain and fatigue scores were measured at baseline and within an hour after each intervention for 6 weeks. Pain and fatigue scores significantly decreased in the aromatherapy massage and reflexology groups compared with the control group (p < .05). The reflexology intervention started to decrease mean pain and fatigue scores earlier than aromatherapy massage (week 1 vs week 2 for pain, week 1 vs week 4 for fatigue) (p < .05). Aromatherapy massage and reflexology are simple and effective nonpharmacologic nursing interventions that can be used to help manage pain and fatigue in patients with rheumatoid arthritis. PMID:27091583

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

    PubMed Central

    2012-01-01

    Introduction Smoking increases the risk of developing rheumatoid arthritis (RA) and affects the severity of established RA. Smoking can impact on Th17 lymphocyte differentiation and function through activation of the aryl hydrocarbon receptor (AHR), a process with implications for the pathogenic mechanisms in RA that involve the cytokine, interleukin (IL)-17A. The objective of this study was to establish any effect of smoking on the inflammatory tissue lesions of rheumatoid arthritis via the AHR and IL-17A. Methods Twenty synovial and eighteen subcutaneous nodule tissue samples from 31 patients with RA were studied. Patient smoking status at the time of tissue collection was established. Expression of AHR, CYP1A1, AHRR, IL6, IL17A, IL17F, IL22, IL23, IL23R, IFNG, TBX21, IDO1 and FOXP3 genes were assessed in tissues and cultured cells using real-time PCR. Two-colour immunofluorescence was used to co-localise AHR and CYP1A1 protein in synovial tissues. The response of monocytes and monocyte-derived dendritic cells (mo-DCs) to the AHR agonist, benzo(a)pyrene (BaP) was compared in vitro. Results AHR gene expression was demonstrated in rheumatoid synovial tissues and nodules with significantly greater expression in synovia. Expression was not influenced by smoking in either tissue. Evidence of AHR activation, indicated by CYP1A1 and AHRR gene expression, was found only in synovia from patients who smoked. However, IL17A gene expression was lower in synovia from smokers. TBX21 and FOXP3 expression was not affected by smoking. Within the synovial tissues of smokers the principal cell type with evidence of AHR activation was a subset of synovial DCs. This observation was consistent with the sensitivity of human mo-DCs to BaP stimulation demonstrated in vitro. Exposure to BaP affected mo-DC function as demonstrated by decreased IL6 expression induced by PolyI:C, without affecting indoleamine 2,3 dioxygenase (IDO)1 expression. Conclusion Our findings show that one effect of

  5. Rheumatoid Arthritis: "You Are Not Alone." | NIH MedlinePlus the Magazine

    MedlinePlus

    ... page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Rheumatoid Arthritis: "You Are Not Alone." Past Issues / Summer 2014 ... Contents Members of the America 2 Anywhere 4 Arthritis (A2A4A) running group after finishing a marathon. Through ...

  6. Polyarticular psoriatic arthritis is more like oligoarticular psoriatic arthritis, than rheumatoid arthritis

    PubMed Central

    Helliwell, P S; Porter, G; Taylor, W J

    2007-01-01

    Background and objective Since the original description of psoriatic arthritis (PsA) subgroups by Moll and Wright, there has been some discrepancy in the precise prevalence of the different subgroups and in particular the proportion of patients with polyarthritis. The higher prevalence of the polyarthritis subgroup may be due to the inclusion of patients with seronegative rheumatoid arthritis with coincidental psoriasis. The classification of psoriatic arthritis (CASPAR) study database provided an opportunity to examine this question. Methods The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician‐diagnosed PsA and 525 controls with other inflammatory arthritis, 70% of whom had rheumatoid arthritis. Patients with PsA were divided into two groups: polyarthritis and non‐polyarthritis (which included the Moll and Wright subgroups of spinal disease, distal interphalangeal predominant and arthritis mutilans) and were compared with patients with rheumatoid arthritis. Comparisons were made between all three groups and, if a significant difference occurred, between the two groups with PsA. Results The three groups differed significantly with regard to all clinical and laboratory variables except duration of disease. Significant differences were also found between the two groups of PsA in terms of age, sex, total number of involved joints, disability score and symmetry. However, no differences were found between the groups of patients with PsA in terms of seropositivity for rheumatoid factor and antibodies to cyclic citrullinated peptide, enthesitis, and spinal pain and stiffness. Further, dactylitis was commonly seen in patients with PsA (57% in the polyarticular group and 45% in non‐polyarticular group), and uncommonly found in patients with rheumatoid arthritis (5%). With the exception of entheseal changes, syndesmophytes and osteolysis, typical radiological features of PsA could not be used to distinguish between the PsA

  7. Nerve Zap Eased Rheumatoid Arthritis in Small Study

    MedlinePlus

    ... gov/news/fullstory_159838.html Nerve Zap Eased Rheumatoid Arthritis in Small Study Treatment worked some for patients ... the gut may help ease stubborn symptoms of rheumatoid arthritis, preliminary research suggests. The study, of 17 adults ...

  8. Bilirubin as a Protective Factor for Rheumatoid Arthritis: An NHANES Study of 2003 - 2006 Data

    PubMed Central

    Fischman, Daniel; Valluri, Ashok; Gorrepati, Venkata Subhash; Murphy, Megan E.; Peters, Ian; Cheriyath, Pramil

    2010-01-01

    Background Rheumatoid arthritis(RA) is a chronic inflammatory, autoimmune polyarthritis, with a prevalence estimated at one percent of the United States(US) population. Serum bilirubin, because of its antioxidant nature, has been conjectured to exert an anti-inflammatory biologic effect. The objective of this study is to discern whether higher serum Total Bilirubin(TBili) levels are protective against RA. Methods This is a secondary analysis of National Health and Nutrition Examination Survey (NHANES) data collected between 2003-2006. Study participants completed a comprehensive questionnaire regarding their health history, underwent a physical examination, and had body fluids collected for laboratory studies. In NHANES, to assess for the presence of RA, the following questions were asked: "Doctor ever said you had arthritis?" If so, "Which type of arthritis". Statistical analysis was performed, using SAS version 9.1, proc survey methods. Participant data were adjusted for demographic characteristics as well as risk factors for RA. Results NHANES 2003-2006 included 20,470 individuals, chosen as a representative sampling of the entire US population. Exclusion criteria included age less than twenty years or liver dysfunction, defined as history of abnormal liver function tests or liver disease. 8,147 subjects did not have any exclusion criteria and were included in the data analysis. RA is inversely related to the serum level of TBili with an odds ratio of 0.679 (95% CI 0.533-0.865) and remained significant even after adjusting for age, gender, race, education, and tobacco history, with an odds ratio 0.749 (95% CI 0.575 - 0.976). Conclusions Our study supports the hypothesis that higher TBili levels are protective against RA. A plausible mechanism for this association would be that the anti-oxidant effects of TBili exert a physiologic anti-inflammatory effect, which provides protection against RA. This explanation is supported by prior studies which show that higher

  9. Rheumatoid arthritis association at 6q23.

    PubMed

    Thomson, Wendy; Barton, Anne; Ke, Xiayi; Eyre, Steve; Hinks, Anne; Bowes, John; Donn, Rachelle; Symmons, Deborah; Hider, Samantha; Bruce, Ian N; Wilson, Anthony G; Marinou, Ioanna; Morgan, Ann; Emery, Paul; Carter, Angela; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Strachan, David; Worthington, Jane

    2007-12-01

    The Wellcome Trust Case Control Consortium (WTCCC) identified nine single SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-5) - 5 x 10(-7) in a genome-wide association screen. One, rs6920220, was unequivocally replicated (trend P = 1.1 x 10(-8)) in a validation study, as described here. This SNP maps to 6q23, between the genes oligodendrocyte lineage transcription factor 3 (OLIG3) and tumor necrosis factor-alpha-induced protein 3 (TNFAIP3). PMID:17982455

  10. Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression

    PubMed Central

    Liagre, Bertrand; Vergne-Salle, Pascale; Corbiere, Cecile; Charissoux, Jean L; Beneytout, Jean L

    2004-01-01

    In the present study, we have shown for the first time that a plant steroid, diosgenin, causes an inhibition of the growth of fibroblast-like synoviocytes from human rheumatoid arthritis, with apoptosis induction associated with cyclooxygenase-2 (COX-2) up-regulation. Celecoxib, a selective COX-2 inhibitor, provoked a large decrease in diosgenin-induced apoptosis even in the presence of exogenous prostaglandin E2, whereas interleukin-1β, a COX-2 inducer, strongly increased diosgenin-induced apoptosis of these synoviocytes. These findings suggest that the proapoptotic effect of diosgenin is associated with overexpression of COX-2 correlated with overproduction of endogenous prostaglandin E2. We also observed a loss of mitochondrial membrane potential, caspase-3 activation, and DNA fragmentation after diosgenin treatment. PMID:15225373

  11. Non-Bacterial Thrombotic Endocarditis in a Patient with Rheumatoid Arthritis

    PubMed Central

    Choi, Jung-Hye; Park, Jeong-Eun; Kim, Jang-Young

    2016-01-01

    Rheumatoid arthritis (RA) is frequently associated with various extra-joint complications. Although rare, thromboembolic complications are associated with high morbidity and mortality. We experienced a very rare case of nonbacterial thrombotic endocarditis (NBTE) and subsequent embolic stroke in a patient with RA. A 72-year-old male with a 15-year history of RA suddenly developed neurologic symptoms of vomiting and dizziness. Brain magnetic resonance imaging revealed recently developed multiple cerebellar and cerebral lacunar infarctions. Echocardiography showed a pulsating mitral valve vegetation involving the posterior cusp of the mitral valve leaflet, which was confirmed as NBTE. Immediate anti-coagulation therapy was started. The NBTE lesion disappeared in follow-up echocardiography after 4 weeks of anti-coagulation treatment. PMID:27275182

  12. Sarcoidosis during etanercept treatment for rheumatoid arthritis in women with a history of bilateral oophorectomy.

    PubMed

    Sawahata, Michiru; Sigiyama, Yukihiko; Yamasawa, Hideaki; Miki, Atsushi; Yamamoto, Hisashi; Muto, Shigeaki; Yamamoto, Hironori; Bando, Masashi

    2016-01-01

    nd in immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Paradoxically, this treatment induces sarcoidosis in a small population of RA patients as a class effect. A safer anti-TNF therapeutic strategy requires understanding of the risk factors for sarcoidosis. In Japan, TNF inhibitor was introduced in 2003. We reviewed 226 consecutive patients (65 men and 161 women) who were newly diagnosed with sarcoidosis between 2003 and 2012 at Jichi Medical University Hospital, Japan. We detected 3 cases in which sarcoidosis developed during etanercept treatment for RA. All 3 cases were women who had undergone bilateral oophorectomy more than 20 years earlier. Taken together with our previous epidemiologic findings of a consistently maintained second peak after menopause in the age-specific distribution of sarcoidosis in women over four decades, long-term insidious ovarian dysfunction was a possible risk factor for sarcoidosis under certain conditions, especially during etanercept treatment. PMID:27537723

  13. Mutated citrullinated vimentin antibodies in rheumatoid arthritis.

    PubMed

    Kuna, Andrea Tesija

    2012-01-18

    Rheumatoid arthritis (RA) is the most common inflammatory systemic autoimmune disease, primarily affecting the peripheral joints. The past decade has been marked with revolutionary changes both in the therapeutic and diagnostic perspectives of RA. The discovery of an RA-specific citrullination-driven immune reaction gave a substantial contribution in the diagnostic approach to RA. Efforts directed towards the identification of the antigenic target specifically recognized by these autoantibodies resulted in the identification of vimentin in citrullinated form as the potential native antigen, among other proteins. Furthermore, it was found that the mutation of vimentin represents an independent trigger of antigenic properties, in addition to citrullination. As a result of this discovery, a commercial ELISA using mutated citrullinated vimentin (MCV) was developed. Increasingly, data now support the use of anti-MCV in RA diagnosis and prognosis for errosion. This review summarizes the research to date on the use of anti-MCV in RA diagnosis and prognosis and its potential use as a therapeutic marker. The pathologic role of these antibodies in RA disease is also discussed. PMID:22037509

  14. Neutrophil gene expression in rheumatoid arthritis.

    PubMed

    Cross, Andrew; Bakstad, Denise; Allen, John C; Thomas, Luke; Moots, Robert J; Edwards, Steven W

    2005-10-01

    There is now a growing awareness that infiltrating neutrophils play an important role in the molecular pathology of rheumatoid arthritis. In part, this arises from the fact that neutrophils have potent cytotoxic activity, but additionally from the fact that inflammatory neutrophils can generate a number of cytokines and chemokines that can have a direct influence on the progress of an inflammatory episode. Furthermore, the molecular properties of inflammatory neutrophils are quite different from those normally found in the circulation. For example, inflammatory neutrophils, but not blood neutrophils, can express cell surface receptors (such as MHC Class II molecules and FcgammaRI) that dramatically alter the way in which these cells can interact with ligands to modulate immune function. Cytokine/chemokine expression and surface expression of these novel cell surface receptors is dependent upon the neutrophil responding to local environmental factors to selectively up-regulate the expression of key cellular components via signalling pathways coupled to transcriptional activation. However, major changes in the expression levels of some proteins are also regulated by post-translational modifications that alter rates of proteolysis, and hence changes in the steady-state levels of these molecules. PMID:16112850

  15. [New assessment method in rheumatoid arthritis].

    PubMed

    Hirata, Shintaro; Tanaka, Yoshiya

    2016-06-01

    To assess disease activity in rheumatoid arthritis (RA), several composite measures have been used. However, more objective indices have been desired due to subjectivity in conventional indices. The Multi-Biomarker Disease Activity(MBDA) score is a novel serum testing based disease activity score ranging 1-100, derived from pre-specified algorithms in combination with 12 biomarkers. The MBDA score not only reflects disease activity in RA, but also is predictive for radiographic progression and risk of flare after drug reduction. Here we review usefulness of the MBDA score in RA. PMID:27311181

  16. Interleukin-18, interleukin-12B and interferon-γ gene polymorphisms in Brazilian patients with rheumatoid arthritis: a pilot study.

    PubMed

    Angelo, H D; Gomes Silva, I I F; Oliveira, R D R; Louzada-Júnior, P; Donadi, E A; Crovella, S; Maia, M M D; de Souza, P R E; Sandrin-Garcia, P

    2015-10-01

    Polymorphisms in interleukin (IL)-18, IL-12 and interferon (IFN)-γ genes are associated with different levels of cytokines expression and have been associated with rheumatoid arthritis (RA). IL-18 +105 A/C, IL-12B +1188 A/C and IFN-γ +874 T/A polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (PCR) and amplification refractory mutation system PCR from 90 RA patients and 186 healthy individuals. There were significant differences to IL-18 +105 A/C polymorphism between the RA and control groups (odds ratio = 3.77; P < 0.0001). Individual carriers of the variant allele C had a 3.77-fold increased risk of for RA (P = 0.0032). No association was observed for IL-12B and IFN-γ polymorphisms. Our finds suggest a possible role for IL-18 polymorphism in the RA susceptibility in studied population. PMID:26302971

  17. 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

  18. AA-negative and Kappa-positive Amyloidosis in a Patient with Rheumatoid Arthritis.

    PubMed

    Ueno, Toshiharu; Sumida, Keiichi; Hoshino, Junichi; Suwabe, Tatsuya; Mise, Koki; Hazue, Ryo; Hayami, Noriko; Hiramatsu, Rikako; Kawada, Masahiro; Imafuku, Aya; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Kinowaki, Keiichi; Ohashi, Kenichi; Fujii, Takeshi; Nishida, Aya; Ubara, Yoshifumi

    2016-01-01

    A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain. Combination therapy with high-dose melphalan and autologous stem cell transplantation was performed according to the regimen for AL amyloidosis. Her proteinuria and RA subsided, but relapsed after 3 years. This is the first report regarding kappa light chain amyloidosis in an RA patient. PMID:27580556

  19. Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Liu, Nathan J.; Chapman, Robert; Lin, Yiyang; Mmesi, Jonas; Bentham, Andrew; Tyreman, Matthew; Abraham, Sonya; Stevens, Molly M.

    2016-02-01

    Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08423g

  20. Serum Trace Element Concentrations in Rheumatoid Arthritis.

    PubMed

    Sahebari, Maryam; Ayati, Razie; Mirzaei, Hamed; Sahebkar, Amirhossein; Hejazi, Sepideh; Saghafi, Massoud; Saadati, Nayyereh; Ferns, Gordon A; Ghayour-Mobarhan, Majid

    2016-06-01

    Rheumatoid arthritis (RA) is a condition that is associated with oxidative stress. Serum trace elements and their related transport proteins, e.g., albumin and ceruloplasmin, play an important role in the antioxidant defense. Trace element status may therefore be involved in the pathogenesis of RA or be affected by the disease activity of this chronic inflammatory condition. The study participants were 110 patients with RA and 100 sex- and age-matched healthy volunteers. Serum concentrations of albumin, ceruloplasmin, selenium, zinc, copper, and zinc/copper ratio were measured in all subjects. The relationship between these parameters and disease activity score was also assessed. Lower concentrations of serum Alb, Zn, and Se were independently related to disease activity index. High concentrations of serum copper were associated with the presence of RA. Serum Cu concentrations were positively related to disease activity as assessed by the disease activity score. Low serum concentrations of Zn and Se, and high serum Cu concentrations may be associated with the presence of RA or be a consequence of this condition. Of the trace elements that were investigated in the present study, only serum Cu was positively correlated with disease activity. PMID:26450515

  1. Olecranon Bursitis Caused by Candida parapsilosis in a Patient with Rheumatoid Arthritis.

    PubMed

    Gamarra-Hilburn, Carla F; Rios, Grissel; Vilá, Luis M

    2016-01-01

    Septic bursitis is usually caused by bacterial organisms. However, infectious bursitis caused by fungi is very rare. Herein, we present a 68-year-old woman with long-standing rheumatoid arthritis who developed pain, erythema, and swelling of the right olecranon bursa. Aspiration of the olecranon bursa showed a white blood cell count of 3.1 × 10(3)/μL (41% neutrophils, 30% lymphocytes, and 29% monocytes). Fluid culture was positive for Candida parapsilosis. She was treated with caspofungin 50 mg intravenously daily for 13 days followed by fluconazole 200 mg orally daily for one week. She responded well to this treatment but had recurrent swelling of the bursa. Bursectomy was recommended but she declined this option. This case, together with other reports, suggests that the awareness of uncommon pathogens, their presentation, and predisposing risk factors are important to establish an early diagnosis and prevent long-term complications. PMID:27595032

  2. Iodine-131 uptake in a patient with thyroid cancer and rheumatoid arthritis during acupuncture treatment

    SciTech Connect

    Otsuka, N.; Fukunaga, M.; Morita, K.; Ono, S.; Nagai, K.; Katagiri, M.; Harada, T.; Morita, R. )

    1990-01-01

    A patient with thyroid carcinoma had abnormal accumulation of I-131 in the areas of both feet and hands on whole body scan. The sites of abnormal accumulation of I-131 were similar to those on bone scintigraphy. The radiographic examination of the lesions showed characteristic findings of rheumatoid arthritis, and the presence of small gold needles for acupuncture treatment was demonstrated. There were no findings of bone metastases. Although the mechanism of accumulation of I-131 in this patient is unknown, interpreters of I-131 whole body scintigraphs should keep this case in mind when acupuncture treatment has been done. The authors can only speculate on a common blood flow mechanism for enhanced HMDP and I-131 uptake in this arthritic patient who had been treated by acupuncture.

  3. Hydroxychloroquine sulphate in the treatment of rheumatoid arthritis: a double blind comparison of two dose regimens.

    PubMed Central

    Pavelka, K; Sen, K P; Pelísková, Z; Vácha, J; Trnavský, K

    1989-01-01

    A controlled, double blind, parallel group, long term study of hydroxychloroquine sulphate in the treatment of rheumatoid arthritis, comparing daily doses of 200 mg and 400 mg, is described. The trial involved 54 patients with moderate disease activity who had not previously received antimalarial drugs. Forty three patients completed the one year treatment. The groups receiving different doses were homogeneous and did not differ in any of the 25 monitored indicators. Both dose regimens were effective, and a significant reduction of disease activity was observed after one year's treatment. Of the nine laboratory and 11 clinical indices of efficacy monitored, no statistically significant differences were reported, but in the group of patients treated with the 400 mg daily dose the number of side effects was three times greater. As there have been no reports of retinopathy with hydroxychloroquine at daily doses of 200 mg the effectiveness of this dose is of practical importance. PMID:2673079

  4. Olecranon Bursitis Caused by Candida parapsilosis in a Patient with Rheumatoid Arthritis

    PubMed Central

    Rios, Grissel

    2016-01-01

    Septic bursitis is usually caused by bacterial organisms. However, infectious bursitis caused by fungi is very rare. Herein, we present a 68-year-old woman with long-standing rheumatoid arthritis who developed pain, erythema, and swelling of the right olecranon bursa. Aspiration of the olecranon bursa showed a white blood cell count of 3.1 × 103/μL (41% neutrophils, 30% lymphocytes, and 29% monocytes). Fluid culture was positive for Candida parapsilosis. She was treated with caspofungin 50 mg intravenously daily for 13 days followed by fluconazole 200 mg orally daily for one week. She responded well to this treatment but had recurrent swelling of the bursa. Bursectomy was recommended but she declined this option. This case, together with other reports, suggests that the awareness of uncommon pathogens, their presentation, and predisposing risk factors are important to establish an early diagnosis and prevent long-term complications. PMID:27595032

  5. Adult rheumatoid arthritis is associated with MC1, a new HLA-D encoded determinant.

    PubMed

    Carpenter, A B; Kahl, L E; Bartkowiak, C D; Duquesnoy, R J; Eisenbeis, C H

    1988-03-01

    We evaluated the association of a new HLA-D encoded determinant, MC1, with adult rheumatoid arthritis (RA). This determinant associates with DR1 and DR4 and can be defined by serological typing. We found MC1 in 83% of 80 patients with RA vs 43% of controls. Although the frequencies of DR1 and DR4 were both significantly increased in patients with RA compared with controls, MC1 had the highest relative risk (6.2) of any HLA-DR antigen tested. MC1 negative and positive populations were not significantly different in any of a variety of clinical and laboratory variables including age, sex, disease duration, age at onset, hours of morning stiffness, functional class, joint count, presence of subcutaneous nodules or bony erosions, frequency of side effects to gold or D-penicillamine, sedimentation rate, and antinuclear antibody. PMID:2454315

  6. Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis.

    PubMed

    Matheson, A J; Figgitt, D P

    2001-01-01

    Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor which has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Rofecoxib has greater selectivity for COX-2 than celecoxib, meloxicam, diclofenac and indomethacin. In well-controlled clinical trials, rofecoxib 12.5 to 500 mg/day has been evaluated for its efficacy in the treatment of osteoarthritis, acute pain and rheumatoid arthritis [lower dosages (5 to 125 mg/day) were generally used in the chronic pain indications]. In the treatment of patients with osteoarthritis, rofecoxib was more effective in providing symptomatic relief than placebo, paracetamol (acetaminophen) and celecoxib and was similar in efficacy to ibuprofen, diclofenac, naproxen and nabumetone. Overall, both the physician's assessment of disease status and the patient's assessment of response to therapy tended to favour rofecoxib. In patients with postsurgical dental pain, pain after spinal fusion or orthopaedic surgery, or primary dysmenorrhoea, rofecoxib provided more rapid and more sustained pain relief and reduced requirements for supplemental morphine use after surgery than placebo. Rofecoxib was more efficacious than celecoxib in patients with acute dental pain and pain after spinal fusion surgery, although celecoxib may have been used at a subtherapeutic dose. In comparison with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac and naproxen sodium, rofecoxib was similar in efficacy in the treatment of acute pain. Although naproxen sodium provided more rapid pain relief than rofecoxib in patients with primary dysmenorrhoea, the reverse was true after orthopaedic surgery: rofecoxib provided more rapid pain relief and less supplemental morphine was needed. Rofecoxib was as effective as naproxen in providing symptomatic relief for over 8700 patients with rheumatoid arthritis. Compared with traditional NSAID therapy, rofecoxib had a significantly lower incidence of endoscopically confirmed

  7. [GWAS of Rheumatoid Arthritis and Drug Discovery].

    PubMed

    Ohmura, Koichiro

    2015-04-01

    We have conducted genome-wide association studies (GWAS) for rheumatoid arthritis (RA). We previously found that myelin basic protein (MBP) is associated with RA. One of the MBP isoforms (Golli-MBP) is expressed not only in nerve cells, but also in hematopoietic cells, and may negatively regulate T-cell receptor signaling. We expanded the GWAS level by collaborating with laboratories in Japan and then throughout the world. Meta-analysis of GWAS data resulted in the identification of -100 genomic loci associated with RA development. The -100 genomic loci contain -400 candidate genes, and it is not easy to find out which genes actually play important roles in RA. By incorporating available public databases, we succeeded in narrowing down the susceptibility genes from 377 to 98. We also showed that regulatory T cells are associated with RA based on the combination of the histone methylation database and our mega-GWAS results. Protein-protein interaction and drug discovery databases gave us information that some of the drugs have already been developed as therapeutic medicines for RA, and some of them were used for diseases other than RA. These drugs may be used for RA in the near future (drug repurposing). The combination of biological databases and GWAS results may be a novel method to identify new therapeutic targets. PMID:26536782

  8. Hypoxia-Inducible Factor (HIF) as a Target for Novel Therapies in Rheumatoid Arthritis

    PubMed Central

    Hua, Susan; Dias, Thilani H.

    2016-01-01

    Hypoxia is an important micro-environmental characteristic of rheumatoid arthritis (RA). Hypoxia-inducible factors (HIF) are key transcriptional factors that are highly expressed in RA synovium to regulate the adaptive responses to this hypoxic milieu. Accumulating evidence supports hypoxia and HIFs in regulating a number of important pathophysiological characteristics of RA, including synovial inflammation, angiogenesis, and cartilage destruction. Experimental and clinical data have confirmed the upregulation of both HIF-1α and HIF-2α in RA. This review will focus on the differential expression of HIFs within the synovial joint and its functional behavior in different cell types to regulate RA progression. Potential development of new therapeutic strategies targeting HIF-regulated pathways at sites of disease in RA will also be addressed. PMID:27445820

  9. Asthma-like symptoms in a patient with rheumatoid arthritis and Adalimumab treatment.

    PubMed

    Mărgineanu, Ioana; Crişan, Radu; Mihăescu, Traian

    2015-01-01

    After the introduction of anti-TNFα medication for treatment of autoimmune conditions, clinicians have investigated not only other possible uses for the drugs, but also less common side-effects and interactions with other pathologies. Despite some succes registered with Adalimumab as an antiinflammatory agent in severe asthma, there have been case reports of patients developing asthma or asthma-like symptoms following anti-TNFα therapy. The case presents a patient without previous family or personal history of respiratory or atopic conditions that developed bronchospasm immediately after the initiation of Adalimumab and Methotrexate treatment for rheumatoid arthritis. Despite the patient presenting asthma characteristics (expiratory wheezing, dry cough, partial reversibility at post bronchodilator test) and asthma medication alleviating simtomathology, biological markers (eosenophil granulocytes in sputum, serum IgE) for asthma are absent. The relationship between bronchospasm and medication and other possible causes for her respiratory symptoms are discussed. PMID:27451592

  10. Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis

    PubMed Central

    Saad, Mohamed N.; Mabrouk, Mai S.; Eldeib, Ayman M.; Shaker, Olfat G.

    2015-01-01

    Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP) approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field. PMID:26843965

  11. A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis

    PubMed Central

    Kirwan, J; Hallgren, R; Mielants, H; Wollheim, F; Bjorck, E; Persson, T; Book, C; Bowman, S; Byron, M; Cox, N; Field, M; Kanerud, L; Leirisalo-Repo, M; Malaise, M; Mohammad, A; Palmer, R; Petersson, I; Ringertz, B; Sheldon, P; Simonsson, M; Snowden, N; Van den Bosch, F

    2004-01-01

    Objectives: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. Methods: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. Results: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. Conclusions: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment. PMID:15140776

  12. A Rare Case of Cardiac Tamponade Induced by Chronic Rheumatoid Arthritis

    PubMed Central

    Yousuf, Tariq; Kramer, Jason; Kopiec, Adam; Bulwa, Zachary; Sanyal, Shuvani; Ziffra, Jeffrey

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease primarily involving the joint synovium. RA is a systemic disease which has many known extra-articular manifestations. We present a unique case of a patient with long standing RA who presented with a primary complaint of chest and back pain. Echocardiography revealed borderline normal left ventricular function and a large pericardial effusion with the finding of elevated intrapericardial pressure suspicious for cardiac tamponade. Infectious workup was all found to be negative. The presence and elevation of anti-cyclic citrullinated peptide antibody, rheumatoid factor and C-reactive protein (CRP) confirmed the patient was having an active flare-up of RA. It was determined that this flare-up was the cause of the cardiac tamponade. A pericardiocentesis was performed and 850 mL of bloody fluid was drained. The patient remained stable following the pericardiocentesis. At his follow-up visit, repeat echocardiogram showed no signs for pericardial effusion. Although there has been extensive study of RA, there are only a few documented cases noting the occurrence of cardiac tamponade in these patients. Therefore, it is important for the clinician to be aware of and recognize this potentially serious cardiac outcome associated with a common rheumatologic condition. PMID:26251689

  13. Serious infection during etanercept, infliximab and adalimumab therapy for rheumatoid arthritis: A literature review.

    PubMed

    Downey, Colum

    2016-06-01

    The purpose of this review is to establish whether there is a significantly increased incidence of serious infections during treatment for rheumatoid arthritis (RA) with etanercept, infliximab or adalimumab, to determine the background risk of serious infection in RA patients without treatment with any biological therapy and to ascertain which organisms are involved in serious infections in RA patients while being treated with etanercept, infliximab or adalimumab. Randomised controlled trials (RCTs), meta-analyses of RCTs, Cochrane reviews, national registry articles and case reports were identified using PubMed/MEDLINE, The Cochrane Library and Google Scholar. The medical subject heading "rheumatoid arthritis" was combined with "serious infection" or "infection" or "adverse drug events" with each of the three reference biological therapies separately: etanercept, infliximab and adalimumab. These electronic searches were limited to human studies, adult studies, those published in the last 10 years (2004-14) and in the English language. Studies which involved the tumor necrosis factor-α inhibitors certolizumab pegol or golimumab were excluded. The background risk of serious infection appears to be approximately two-fold more than non-RA patients before any treatment with biological therapy. The national registries, which may represent the typical RA patient more accurately than clinical trials, suggest a small but significantly increased incidence of serious infection ranging 1.2-2.78 times that of control (treatment with methotrexate). Mycobacteria spp., Staphyloccus aureus, Listeria monocytogenes, Varicella zoster virus and Leishmania species (spp.) repeatedly appear in the case report literature and should be in the mind of the clinician faced with a serious infection in a RA patient with an unknown pathogen who is being treated with either etanercept, infliximab or adalimumab. PMID:26200188

  14. Anti-Sa antibodies: prognostic and pathogenetic significance to rheumatoid arthritis

    PubMed Central

    El-Gabalawy, Hani S; Wilkins, John A

    2004-01-01

    Anti-Sa antibodies are detected in the serum of 20–47% of patients with rheumatoid arthritis. These antibodies have a high degree of specificity for the disease, and appear to identify a subset of early rheumatoid arthritis patients destined to have aggressive and destructive disease. It has recently been confirmed that anti-Sa antibodies are directed to citrullinated vimentin, thus placing them in the anti-citrulline family of autoantibodies. The Sa antigen has previously been shown to be present in synovium. This, along with the demonstration of citrullinated proteins in rheumatoid synovium, suggests that anti-Sa antibodies may play a pathogenetic role in the initiation and/or persistence of rheumatoid synovitis. PMID:15059270

  15. Anti-Carbamylated Protein Antibodies as a Reproducible Independent Type of Rheumatoid Arthritis Autoantibodies

    PubMed Central

    Montes, Ariana; Regueiro, Cristina; Perez-Pampin, Eva; Boveda, Maria Dolores; Gomez-Reino, Juan J.; Gonzalez, Antonio

    2016-01-01

    A large fraction of the patients with rheumatoid arthritis (RA) develop specific autoantibodies, which until recently were only of two types, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). We aimed to replicate important findings about a recently described third type of specific autoantibodies, anti-carbamylated protein (anti-CarP) antibodies, because they have been described based only in the homemade ELISA from a single laboratory. Our study included 520 patients with established RA and 278 healthy controls of Spanish ancestry and it was done with an independently performed ELISA. The prevalence and pattern of environmental, clinical and genetic associations of the anti-CarP antibodies were similar to the previously described. Notably, the presence and titers of anti-CarP correlated with the presence and titers of ACPA, but the anti-CarP antibodies did not share the known genetic and exposure risk factors of the ACPA. In addition, anti-CarP antibodies were independently associated with a higher (10.5%) prevalence of bone erosions. The reproducibility of these characteristics across laboratories and European subpopulations, indicates the wide validity of the results and suggests that determination of anti-CarP antibodies could contribute to explain RA pathogenesis and identify clinically relevant patient subgroups. PMID:27537849

  16. Fibrates as therapy for osteoarthritis and rheumatoid arthritis? A systematic review

    PubMed Central

    van Eekeren, Inge C.M.; Bastiaansen-Jenniskens, Yvonne M.; Lubberts, Eric; Verhaar, Jan A.N.; van Osch, Gerjo J.V.M.; Bierma-Zeinstra, Sita M.

    2013-01-01

    Fibrates are used as lipid-lowering drugs to prevent cardiovascular pathology. Fibrates are ligands of peroxisome proliferator-activated receptor α (PPARα). Besides altering lipid metabolism, PPARα ligands exert anti-inflammatory effects on various cell types. In this study, we hypothesized that PPARα agonists exert beneficial effects on osteoarthritis (OA) and rheumatoid arthritis (RA) by their local anti-inflammatory effects, but also by their systemic influences. A systematic literature search of Medline and EMBASE databases was performed up to August 2011. The main search items were osteoarthritis, rheumatoid arthritis, peroxisome proliferator-activated receptor alpha and fibrates. Inclusion criteria were in vivo or in vitro studies regarding humans or animals in which the effects of PPARα ligands were studied. Six in vivo human studies, four in vivo animal studies and seven in vitro studies were included. The in vivo human studies showed all beneficial clinical effects of PPARα ligands, but studies were small and only four were randomized. Ligands for PPARα significantly reduced pain, swelling of the joints and decreased systemic inflammatory markers. In vitro and in vivo animal studies indicate that PPARα agonists inhibit bone resorption, and reduce inflammatory and destructive responses in cartilage and synovium. PPARα agonists such as fibrates should be considered as potential therapeutic strategy for RA. There is no clinical evidence for their use in OA, although in vitro studies indicate that PPARα agonists demonstrate different joint-protective effects locally, and systemic effects on inflammation, serum lipid levels and vascular pathology. Animal studies should be performed and after confirmation of the protective effects of PPARα, large randomized controlled trials could investigate fibrates in OA and RA. PMID:23515070

  17. Cardiovascular Disease in Rheumatoid Arthritis: A Systematic Literature Review in Latin America

    PubMed Central

    Sarmiento-Monroy, Juan Camilo; Amaya-Amaya, Jenny; Espinosa-Serna, Juan Sebastián; Herrera-Díaz, Catalina; Anaya, Juan-Manuel; Rojas-Villarraga, Adriana

    2012-01-01

    Background. Cardiovascular disease (CVD) is the major predictor of poor prognosis in rheumatoid arthritis (RA) patients. There is an increasing interest to identify “nontraditional” risk factors for this condition. Latin Americans (LA) are considered as a minority subpopulation and ethnically different due to admixture characteristics. To date, there are no systematic reviews of the literature published in LA and the Caribbean about CVD in RA patients. Methods. The systematic literature review was done by two blinded reviewers who independently assessed studies for eligibility. The search was completed through PubMed, LILACS, SciELO, and Virtual Health Library scientific databases. Results. The search retrieved 10,083 potential studies. A total of 16 articles concerning cardiovascular risk factors and measurement of any cardiovascular outcome in LA were included. The prevalence of CVD in LA patients with RA was 35.3%. Non-traditional risk factors associated to CVD in this population were HLA-DRB1 shared epitope alleles, rheumatoid factor, markers of chronic inflammation, long duration of RA, steroids, familial autoimmunity, and thrombogenic factors. Conclusions. There is limited data about CVD and RA in LA. We propose to evaluate cardiovascular risk factors comprehensively in the Latin RA patient and to generate specific public health policies in order to diminish morbi-mortality rates. PMID:23193471

  18. Organizing Pneumonia in Rheumatoid Arthritis Patients: A Case-Based Review

    PubMed Central

    Mori, Shunsuke; Koga, Yukinori; Sugimoto, Mineharu

    2015-01-01

    We treated 21 patients with organizing pneumonia (OP) associated with rheumatoid arthritis (RA) or related to biological disease-modifying antirheumatic drugs (DMARDs) at our institution between 2006 and 2014. Among these cases, 3 (14.3%) preceded articular symptoms of RA, 4 (19.0%) developed simultaneously with RA onset, and 14 (66.7%) occurred during follow-up periods for RA. In the case of OP preceding RA, increased levels of anti-cyclic citrullinated peptide antibodies and rheumatoid factor were observed at the OP onset. RA disease activity was related to the development of OP in the simultaneous cases. In the cases of OP developing after RA diagnosis, 10 of 14 patients had maintained low disease activity with biological DMARD therapy at the OP onset, and among them, 6 patients developed OP within the first year of this therapy. In the remaining four patients, RA activity was not controlled at the OP onset. All patients responded well to systemic steroid therapy, but two patients suffered from relapses of articular and pulmonary symptoms upon steroid tapering. In most of the RA patients, DMARD therapy was introduced or restarted during the steroid tapering. We successfully restarted a biological DMARD that had not been previously used for patients whose RA would otherwise have been difficult to control. In this study, we also perform a review of the literature on RA-associated or biological DMARD-related OP and discuss the pathogenesis and management of OP occurring in RA patients. PMID:26543387

  19. Femoral nerve palsy caused by a huge iliopectineal synovitis extending to the iliac fossa in a rheumatoid arthritis case.

    PubMed

    Tatsumura, Masaki; Mishima, Hajime; Shiina, Itsuo; Hara, Yuki; Nishiura, Yasumasa; Ishii, Tomoo; Ochiai, Naoyuki; Ishii, Wataru; Sumida, Takayuki

    2008-01-01

    We report on a 54-year-old woman with rheumatoid arthritis who had severe femoral nerve palsy affected by a distended synovium in the hip joint. Surgical exploration demonstrated a perforation of the iliopectineal bursa connecting with the hip joint. The patient fully recovered from femoral nerve palsy after surgery. It was considered that synovitis of the hip joint had developed following huge iliopectineal bursitis. PMID:18180875

  20. A case of emphysematous pyelonephritis in a patient with rheumatoid arthritis taking corticosteroid and low-dose methotrexate.

    PubMed

    Watanabe, Hiroshi; Suzuki, Ryoma; Asano, Tomoyuki; Shio, Kiori; Iwadate, Haruyo; Kobayashi, Hiroko; Matsuoka, Toshimitsu; Aikawa, Ken; Ohira, Hiromasa

    2010-05-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid-induced diabetes mellitus who was taking corticosteroid and low-dose methotrexate. PMID:20536605

  1. A comparative study of the effects of bucillamine and salazosulfapyridine in the treatment of rheumatoid arthritis.

    PubMed

    Nakajima, Mikio; Ueda, Naoki; Ohara, Hidetsugu; Abe, Muneaki; Kinoshita, Mitsuo

    2009-01-01

    Bucillamine (Buc), developed in Japan, is a disease-modifying antirheumatic drug (DMARD) which has been used to treat numerous patients with rheumatoid arthritis (RA) in Japan and Korea with favorable results. However, it has not been used globally. In the present study, we compared the timing of onset of efficacy and the usefulness of this drug with that of the globally accepted agent salazosulfapyridine (SASP). There were 26 patients in the Buc group and 23 in the SASP group. We compared changes in the number of swollen joints, number of painful joints, duration of morning stiffness, grip strength, levels of inflammatory marker [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], rheumatoid factor (RF), physician's rating by visual analogue scale (VAS), patient's rating of pain, patient's overall rating (VAS), and improvement according to European League against Rheumatism (EULAR) criteria (DAS28-CRP, DAS28-ESR) in these two groups of patients. Both Buc and SASP were shown to be efficacious within 3 months after the start of treatment. Both drugs were found to be suitable as first-line treatment of early RA. Signs of efficacy tended to occur earlier with Buc than with SASP, and Buc also tended to have higher efficacy than SASP. PMID:19363607

  2. Development of a functional scoring system for rheumatoid arthritis patients with cervical myelopathy.

    PubMed Central

    Casey, A T; Bland, J M; Crockard, H A

    1996-01-01

    OBJECTIVE: To be able to measure disability objectively in rheumatoid arthritis complicated by cervical myelopathy. METHODS: The responses to the Stanford health assessment questionnaire disability index were recorded from 250 consecutive patients (group 1) referred to our unit for spinal surgery. Using principal components analysis the questionnaire was reduced from 20 questions to 10 questions. In the second part of the study, the results of the questionnaire for those patients undergoing surgery from the original group of 250 patients were analysed with respect to outcome. RESULTS: The reduction in the number of questions results in no significant loss of information, reliability (internal consistency Cronbach's alpha = 0.968) or sensitivity. The new scale, the myelopathy disability index, measures only one dimension (Eigen value 6.97) and may be more finely tuned to the measurement of disability in these myelopathic patients. When administered to the 194 patients undergoing cervical spine (group 2) surgery the myelopathy disability index was an accurate predictor of neurological and functional outcome, as well as survival following surgery (P < 0.0001). CONCLUSIONS: The myelopathy disability index provides a much needed objective and reliable means of assessing disability in patients with rheumatoid involvement of the cervical spine and also in predicting outcome following surgical intervention. It also provides information for both the patient and surgeon alike, on what to realistically expect from surgery. Its adoption should facilitate comparisons between different forms of surgical intervention. PMID:9014584

  3. Anti-Citrullinated Peptide Antibody (ACPA) Assays and their Role in the Diagnosis of Rheumatoid Arthritis

    PubMed Central

    Aggarwal, Rohit; Liao, Katherine; Nair, Raj; Ringold, Sarah; Costenbader, Karen H.

    2010-01-01

    Increasingly, assays for the detection of anti-citrullinated peptide antibodies (ACPA) are used in RA diagnosis. This review summarizes the biologic basis and development of ACPA assays, available ACPA assays and their performance characteristics, and diagnostic properties of ACPA alone and compared to rheumatoid factor (RF) in early RA. We also review correlations, precision, costs and cost-effectiveness, availability, stability and reproducibility of the available assays. Taken together, data indicate that ACPA has a higher specificity than RF for early RA, good predictive validity, high sensitivity, apparent cost-effectiveness and good stability and reproducibility. Given its superior performance characteristics and increasing availability, ACPA is emerging as the most useful single assay for the diagnosis of RA. PMID:19877103

  4. Subcorneal pustular dermatosis associated with rheumatoid arthritis and raised IgA: simultaneous remission of skin and joint involvements with dapsone treatment.

    PubMed Central

    Roger, H; Thevenet, J P; Souteyrand, P; Sauvezie, B

    1990-01-01

    A 44 year old white woman with rheumatoid arthritis for 19 years developed subcorneal pustular dermatosis. She had increased polyclonal IgA and IgA rheumatoid factor. After 4 months' treatment with dapsone 100 mg daily the patient had neither skin lesions nor active joint disease. Images PMID:2181947

  5. [Trends in orthopaedic surgery for patients with rheumatoid arthritis].

    PubMed

    Matsumoto, Takumi; Tanaka, Sakae

    2015-12-01

    Significant advancement in pharmacological treatment including biological agents has gradually changed the role and content of surgical treatments for patients with rheumatoid arthritis. The number of joint replacements in the large joints of lower limbs has decreased, while the number of surgeries in the small joints of hand and feet has increased. Favorable disease control by pharmacological treatment has changed the needs of patients for surgeries and expanded the options of operative procedures for surgeons. The changing needs of patients demanding the higher level of quality of life may seek a change in the surgical treatments. PMID:26608856

  6. 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

  7. Abatacept: a review of its use in the management of rheumatoid arthritis.

    PubMed

    Keating, Gillian M

    2013-07-01

    The biological disease-modifying antirheumatic drug abatacept (Orencia) has a novel mechanism of action; its activity is mediated via the selective modulation of T cell co-stimulation. This article reviews the clinical efficacy and tolerability of intravenous and subcutaneous abatacept in patients with rheumatoid arthritis (RA) and intravenous abatacept in patients with juvenile idiopathic arthritis (JIA), as well as summarizing its pharmacological properties. In patients with RA, the beneficial effects of intravenous or subcutaneous abatacept on signs and symptoms, disease activity, the progression of structural damage, physical function and/or health-related quality of life were seen in a number of well-designed trials, including in methotrexate-naive patients with early RA and poor prognostic factors and in patients with established RA and an inadequate response to either methotrexate or anti-tumour necrosis factor therapy. Subcutaneous abatacept plus methotrexate was also noninferior to subcutaneous adalimumab plus methotrexate in patients with active RA who were naive to biological therapy and had an inadequate response to methotrexate. In paediatric patients with JIA, intravenous abatacept improved signs and symptoms and delayed the time to flare. Abatacept was generally well tolerated in RA and JIA and was associated with low rates of immunogenicity. In conclusion, abatacept is an important option for use in the treatment of RA and JIA. PMID:23794171

  8. Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis

    PubMed Central

    2014-01-01

    Introduction Although previous studies found that cigarette smoking is associated with risk of rheumatoid arthritis (RA), the dose-response relationship remains unclear. This meta-analysis quantitatively summarizes accumulated evidence regarding the association of lifelong exposure to cigarette smoking assessed as pack-years with the risk of RA. Methods Relevant studies were identified by a search of MEDLINE and EMBASE from 1966 to October 2013, with no restrictions. Reference lists from retrieved articles were also reviewed. Studies that reported relative risks (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between pack-years of cigarette smoking and rheumatoid arthritis were included in a dose-response random-effects meta-regression analysis. Results We included 3 prospective cohorts and 7 case-control studies in the meta-analysis. They included a total of 4,552 RA cases. There was no indication of heterogeneity (Pheterogeneity = 0.32) and publication bias did not affect the results. Compared to never smokers, the risk of developing RA increased by 26% (RR = 1.26, 95% CI 1.14 to 1.39) among those who smoked 1 to 10 pack-years and doubled among those with more than 20 pack-years (RR for 21 to 30 pack years = 1.94, 95% CI 1.65 to 2.27). The risk of RA was not increasing further for higher exposure levels (RR for >40 pack-years = 2.07, 95% CI 1.15 to 3.73). The risk of RA was statistically significantly higher among rheumatoid factor (RF)-positive RA cases (RR = 2.47, 95% CI 2.02 to 3.02) compared to RF-negative (RR = 1.58, 95% CI 1.15 to 2.18) when comparing the highest versus lowest category of pack-years for the individual studies. Conclusions Lifelong cigarette smoking was positively associated with the risk of RA even among smokers with a low lifelong exposure. The risk of RA did not further increase with an exposure higher than 20 pack-years. PMID:24594022

  9. Rheumatoid Arthritis of the Foot and Ankle.

    PubMed

    Abdo; Iorio

    1994-11-01

    Rheumatoid arthritis of the foot and ankle can be a debilitating problem, particularly for patients who have undergone successful hip or knee arthroplasty. Optimal medical management, use of orthotic devices, and surgical intervention are essential components of patient care. Forefoot involvement with hallux valgus and lesser metatarsophalangeal joint subluxation and dislocation are the most common findings. Reconstruction usually requires lesser metatarsophalangeal joint excisional arthroplasty and first metatarsophalangeal joint arthrodesis. Midfoot tarsometatarsal and intertarsal involvement is treated with orthotic devices and intertarsal fusion for advanced arthropathy. Hindfoot involvement frequently leads to pes planovalgus deformity, which may require isolated talonavicular arthrodesis if treated early or triple arthrodesis for advanced destruction. Ankle involvement is less frequent; when it is unresponsive to conservative measures, ankle symptoms may be improved by arthrodesis. Although great advances have been made in medical and surgical management of rheumatoid arthritis, the disease remains a serious problem. Through prudent use of medical management, orthotic devices, and other conservative measures as well as surgical intervention, long-term function can be enhanced greatly. PMID:10709025

  10. Laser transillumination for diagnosis of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Boerner, E.; Podbielska, H.; Bauer, J.; Dmochowska, L.; Dziewięcka, M.

    2006-02-01

    In this work, the special portable apparatus was constructed for performing the transillumination examination on interphalangeal joints of patients suffering from rheumatoid arthritis. It consisted of He-Ne laser with optics for collimated illumination, special holder for placing the finger (perpendicular to optical axis, dorsal site towards camera), and CCD camera with memory stick. The captured images in JPEG format with 1152x864 resolution were converted into the gray level pictures and analyzed by means of image processing program from OPTIMAS. 35 ill patients and 11 healthy volunteers were examined. The histograms and 35 luminances were calculated. The average function was applied in order to calculate the mean gray level values in images of corresponding fingers of healthy subjects. These values were compared with values calculated for ill persons. We proved that that transillumination images may have a diagnostic value. For RA suffering patients the corresponding transillumination images represented the lower gray level values than the average value of finger of health volunteers. For II finger of left hand 96% images of ill persons have lower gray level and in case of right hand it was 93%. This proves that basing in transillumination one can diagnose with high probability the patient with rheumatoid arthritis.

  11. 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…

  12. Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene

    PubMed Central

    Michou, Laëtitia; Lasbleiz, Sandra; Rat, Anne-Christine; Migliorini, Paola; Balsa, Alejandro; Westhovens, René; Barrera, Pilar; Alves, Helena; Pierlot, Céline; Glikmans, Elodie; Garnier, Sophie; Dausset, Jean; Vaz, Carlos; Fernandes, Manuela; Petit-Teixeira, Elisabeth; Lemaire, Isabelle; Pascual-Salcedo, Dora; Bombardieri, Stefano; Dequeker, Jan; Radstake, Timothy R.; Van Riel, Piet; van de Putte, Leo; Lopes-Vaz, Antonio; Prum, Bernard; Bardin, Thomas; Dieudé, Philippe; Cornélis, François

    2007-01-01

    The tyrosine phosphatase PTPN22 allele 1858T has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. RA is the most frequent of those multifactorial diseases. The RA association was usually restricted to serum rheumatoid factor positive disease (RF+). No interaction was shown with HLA-DRB1, the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of ≈5% on average and large variations of population allele frequencies (2.1–15.5%). In multifactorial diseases, the final proof for a new susceptibility allele is provided by departure from Mendel's law (50% transmission from heterozygous parents). For PTPN22–1858T allele, convincing linkage proof was available only for type 1 diabetes. We aimed at providing this proof for RA. We analyzed 1,395 West European Caucasian individuals from 465 “trio” families. We replicated evidence for linkage, demonstrating departure from Mendel's law in this subset of early RA onset patients. We estimated the overtransmission of the 1858T allele in RF+ families: T = 63%, P < 0.0007. The 1858T allele frequency increased from 11.0% in controls to 17.4% in RF+ RA for the French Caucasian population and the susceptibility genotype (1858T/T or T/C) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2–2.8)]. In conclusion, we provided the linkage proof for the PTPN22–1858T allele and RF+ RA. With diabetes and RA, PTPN22 is therefore a “linkage-proven” autoimmunity gene. PTPN22 accounting for ≈1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases. PMID:17237219

  13. Social, Health, and Age Differences Associated with Depressive Disorders in Women with Rheumatoid Arthritis

    ERIC Educational Resources Information Center

    Plach, Sandra K.; Napholz, Linda; Kelber, Sheryl T.

    2005-01-01

    Depression in women with rheumatoid arthritis (RA) may be related to social role experiences, physical health, and age. The purpose of this study was to examine the social and health factors contributing to depression in two age groups of women with RA. One-hundred and thirty-eight midlife and late-life women with a diagnosis of RA participated in…

  14. Infections With Biologics in Rheumatoid Arthritis and Related Conditions: a Scoping Review of Serious or Hospitalized Infections in Observational Studies.

    PubMed

    Singh, Jasvinder A

    2016-10-01

    Biologic use is a major advance in the treatment of several autoimmune conditions, including rheumatoid arthritis. In this review, we summarize key studies of serious/hospitalized infections in rheumatoid arthritis (RA). RA is a risk factor for infections. High RA disease activity is associated with higher risk of serious infection. The risk of serious infections with tumor necrosis factor inhibitor (TNFi) biologics is increased in the first 6 months of initiating therapy, and this risk was higher compared to the use of traditional disease-modifying anti-rheumatic drugs (DMARDs). Emerging data also suggest that biologics may differ from each other regarding the risk of serious or hospitalized infections. Past history of serious infections, glucocorticoid dose, and older age were other important predictors of risk of serious infections in patients treated with biologics. PMID:27613285

  15. Radial deviation of the finger caused by an occult intramuscular ganglion in a patient with rheumatoid arthritis.

    PubMed

    Kato, Tomoyuki; Iwamoto, Takuji; Matsumura, Noboru; Sato, Kazuki; Nakamura, Toshiyasu; Toyama, Yoshiaki

    2016-07-01

    Ulnar deviation is a common complication in patients with rheumatoid arthritis (RA). We report a case of an unusual radial deviation of the middle finger caused by an occult intramuscular ganglion of the second interosseous muscle (IOM) in a patient with RA. The resection of the ganglion did not resolve the problem, and the full range of motion of the metacarpophalangeal (MP) joint was achieved through dissection of the tendon of the second dorsal IOM. PMID:24834463

  16. Fatigue in rheumatoid arthritis; a persistent problem: a large longitudinal study

    PubMed Central

    van Steenbergen, Hanna W; Tsonaka, Roula; Huizinga, Tom W J; Boonen, Annelies; van der Helm-van Mil, Annette H M

    2015-01-01

    Objective Fatigue is prevalent and disabling in rheumatoid arthritis (RA). Surprisingly, the long-term course of fatigue is studied seldom and it is unclear to what extent it is influenced by inflammation. This study aimed to determine the course of fatigue during 8 years follow-up, its association with the severity of inflammation and the effect of improved treatment strategies. Methods 626 patients with RA included in the Leiden Early Arthritis Clinic cohort were studied during 8 years. Fatigue severity, measured on a 0–100 mm scale, and other clinical variables were assessed yearly. Patients included in 1993–1995, 1996–1998 and 1999–2007 were treated with delayed treatment with disease-modifying antirheumatic drugs (DMARDs), early treatment with mild DMARDs and early treatment with methotrexate respectively. After multiple imputation, the serial measurements were analysed using linear quantile mixed models. Results Median fatigue severity at baseline was 45 mm and remained, despite treatment, rather stable thereafter. Female gender (effect size=4.4 mm), younger age (0.2 mm less fatigue/year), higher swollen and tender joint counts (0.3 mm and 1.0 mm more fatigue/swollen or tender joint) and C reactive protein-levels (0.1 mm more fatigue per mg/L) were independently and significantly (p<0.05) associated with fatigue severity over 8 years. Although improved treatment strategies associated with less severe radiographic progression, there was no effect on fatigue severity (p=0.96). Conclusions This largest longitudinal study on fatigue so far demonstrated that the association between inflammation and fatigue is statistically significant but effect sizes are small, suggesting that non-inflammatory pathways mediate fatigue as well. Improved treatment strategies did not result in less severe fatigue. Therefore, fatigue in RA remains an ‘unmet need’. PMID:26509063

  17. A Cytokine Signalling Network for the Regulation of Inducible Nitric Oxide Synthase Expression in Rheumatoid Arthritis.

    PubMed

    Dey, Poulami; Panga, Venugopal; Raghunathan, Srivatsan

    2016-01-01

    In rheumatoid arthritis (RA), nitric oxide (NO) is implicated in inflammation, angiogenesis and tissue destruction. The enzyme inducible nitric oxide synthase (iNOS) is responsible for the localised over-production of NO in the synovial joints affected by RA. The pro- and anti-inflammatory cytokines stimulate the synovial macrophages and the fibroblast-like synoviocytes to express iNOS. Therefore, the cytokine signalling network underlying the regulation of iNOS is essential to understand the pathophysiology of the disease. By using information from the literature, we have constructed, for the first time, the cytokine signalling network involved in the regulation of iNOS expression. Using the differential expression patterns obtained by re-analysing the microarray data on the RA synovium and the synovial macrophages available in the Gene Expression Omnibus (GEO) database, we aimed to establish the role played by the network genes towards iNOS regulation in the RA synovium. Our analysis reveals that the network genes belonging to interferon (IFN) and interleukin-10 (IL-10) pathways are always up-regulated in the RA synovium whereas the genes which are part of the anti-inflammatory transforming growth factor-beta (TGF-β) signalling pathway are mostly down-regulated. We observed a consistent up-regulation of the transcription factor signal transducers and activators of transcription 1 (STAT1) in the RA synovium and the macrophages. Interestingly, we found a consistent up-regulation of the iNOS interacting protein ras-related C3 botulinum toxin substrate 2 (RAC2) in the RA synovium as well as the macrophages. Importantly, we have constructed a model to explain the impact of IFN and IL-10 pathways on Rac2-iNOS interaction leading to over-production of NO and thereby causing chronic inflammation in the RA synovium. The interplay between STAT1 and RAC2 in the regulation of NO could have implications for the identification of therapeutic targets for RA. PMID:27626941

  18. Marked Multiple Tendinitis at the Onset of Rheumatoid Arthritis in a Patient with Heterozygous Familial Hypercholesterolemia: Ultrasonographic Observation

    PubMed Central

    Okamoto, Akiko

    2014-01-01

    A 59-year-old woman who had been diagnosed with heterozygous familial hypercholesterolemia developed rheumatoid arthritis (RA). She presented with marked tendinitis of the Achilles tendons, patellar tendons, and finger extensor tendons at the onset of RA. Ultrasonographic examination revealed that tendon lesions were predominantly tendinitis rather than paratenonitis, and that the tendinitis was of the noninsertional variety, rather than the insertional variety. Preexisting tendon xanthomas might have contributed to the unusually dominant noninsertional tendinitis of multiple tendons. PMID:25013736

  19. Circulating interleukin-6 and rheumatoid arthritis: A Mendelian randomization meta-analysis.

    PubMed

    Li, Bing; Xiao, Yu; Xing, Dan; Ma, Xin-Long; Liu, Jun

    2016-06-01

    Interleukin-6 (IL-6), as a pleiotropic cytokine, has been demonstrated to be closely associated with the pathogenisis of rheumatoid arthritis (RA). However, whether this association is causal or not remains unclear, because of the multifactorial role of IL-6 and related confounding factors. We aimed to evaluate the causal relevance between circulating IL-6 levels and the risk of RA through meta-analytical Mendelian randomization approach. IL-6 gene -174G/C variant was selected as an instrument in this Mendelian randomization meta-analysis. Article identification and data collection were conducted in duplicate and independently by 2 authors. The STATA software was used for data analysis. In total, 15 and 5 articles on the association of the -174G/C variant with RA risk and circulating IL-6 level, respectively, were included. The overall analysis showed that C allelic and GC+CC genotype were significantly with 1.59-fold (95% CI: 1.19-2.14) and 1.63-fold (95% CI: 1.17-2.26) increased risk of developing RA, respectively. Asian populations showed stronger association with 4.55-fold (95% CI: 1.62-12.75), 1.84-fold (95% CI: 1.13-2.99), and 4.69-fold (95% CI: 1.68-13.14) increased RA risk in carriers of -174C allelic, CC, and GC+CC genotype, respectively. Carriers of GC+CC genotype showed significant reduction in the circulating IL-6 level compared with GG carriers (WMD = -0.77; 95% CI: -1.16 to -0.38; P = 0.000) in overall populations. Mendelian randomization presented 6% and 22% increased risk of RA with 0.1 pg/mL reduction of circulating IL-6 level in overall and Asian populations, respectively. This Mendelian randomization meta-analysis demonstrated that the long-term genetically reduced circulating IL-6 level might be causally related to a higher risk of RA, especially in Asian populations. PMID:27281095

  20. A case of surgically treated peristomal pyoderma gangrenosum in a patient with rheumatoid arthritis.

    PubMed

    Khajehnoori, Masoomeh; O'Brien, Tim

    2016-01-01

    Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that is difficult to diagnose and treat. It is characterized by the rapid progression of painful necrotic ulcer surrounding an area of abdominal stoma. It is almost exclusively associated with inflammatory bowel disease even after bowel surgery and is associated with significant morbidity. Diagnosis of pyoderma gangrenosum is based on exclusion of other disorders replicating some of its clinical features and histopathological evidence.This is a case report of a 56-year-old lady with rheumatoid arthritis who presented with rapidly progressing abdominal ulcer 8 months after a Hartmanns procedure for perforated diverticulitis. The ulcer had formed a large cavity causing faecal filling in the dependent defect. The other causes of ulcer were excluded with negative histopathology, negative polymerase chain reaction for Mycobacterium ulcerans and negative acid fast bacillus (AFB) test. She was diagnosed with PPG which is routinely treated medically due to risk of setting off a second focus of pyoderma if surgically intervened. However due to increased risk of faecal peritonitis, it was decided to proceed with surgical debridement. This article will discuss the case in more detail and briefly discuss diagnosis and treatment options for PPG. PMID:27302499

  1. Allergic bronchopulmonary aspergillosis in a patient with rheumatoid arthritis under adalimumab therapy: a case report.

    PubMed

    Kawasaki, Tatsuya; Kamiya, Mari; Nakagawa, Atsushi; Takagiwa, Jun; Kawahara, Yutaka; Nonomura, Yoshinori

    2016-01-01

      A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) was admitted to our hospital because of a wet cough that persisted for 1 month. The patient had been taking methotrexate (MTX) and adalimumab (ADA) for the past 3 years, and disease activity of RA was low. Discontinuation of ADA and MTX and treatment with oral levofloxacin were not effective. On admission, laboratory examinations showed eosinophilia (2539/μL), elevated serum total immunoglobulin E (538.0 IU/ml) and Aspergillus-specific immunoglobulin E levels, and Aspergillus fumigatus serum precipitins. A chest radiograph revealed multiple bilateral pulmonary shadows, and computed tomography revealed multiple consolidations. Bronchoscopic examination showed mucous plugs. Pathological examination revealed diffuse infiltration of eosinophils and fungus in the plugs. These findings led to the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). A combination of prednisolone (0.5 mg/kg/day) and itraconazole (200 mg/day) was administered. After 3 months, the pulmonary consolidations resolved. To our knowledge, this is the first report of ABPA in a patient with RA treated with ADA. If patients treated with biologic disease-modifying antirheumatic drugs present with eosinophilia and pulmonary consolidations, clinicians should consider ABPA in the differential diagnosis. PMID:27181240

  2. A case of surgically treated peristomal pyoderma gangrenosum in a patient with rheumatoid arthritis

    PubMed Central

    Khajehnoori, Masoomeh; O'Brien, Tim

    2016-01-01

    Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that is difficult to diagnose and treat. It is characterized by the rapid progression of painful necrotic ulcer surrounding an area of abdominal stoma. It is almost exclusively associated with inflammatory bowel disease even after bowel surgery and is associated with significant morbidity. Diagnosis of pyoderma gangrenosum is based on exclusion of other disorders replicating some of its clinical features and histopathological evidence. This is a case report of a 56-year-old lady with rheumatoid arthritis who presented with rapidly progressing abdominal ulcer 8 months after a Hartmanns procedure for perforated diverticulitis. The ulcer had formed a large cavity causing faecal filling in the dependent defect. The other causes of ulcer were excluded with negative histopathology, negative polymerase chain reaction for Mycobacterium ulcerans and negative acid fast bacillus (AFB) test. She was diagnosed with PPG which is routinely treated medically due to risk of setting off a second focus of pyoderma if surgically intervened. However due to increased risk of faecal peritonitis, it was decided to proceed with surgical debridement. This article will discuss the case in more detail and briefly discuss diagnosis and treatment options for PPG. PMID:27302499

  3. A clinical exploratory study with itolizumab, an anti-CD6 monoclonal antibody, in patients with rheumatoid arthritis

    PubMed Central

    Rodriguez, Pedro C.; Torres-Moya, Roberto; Reyes, Gil; Molinero, Claudino; Prada, Dinorah; Lopez, Ana M.; Hernandez, Isabel M.; Hernandez, Maria V.; Martinez, Jose P.; Hernandez, Xochel; Casaco, Angel; Ramos, Mayra; Avila, Yisel; Barrese, Yinet; Montero, Enrique; Hernandez, Patricia

    2012-01-01

    T cells are involved in the pathogenesis of rheumatoid arthritis (RA). CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes, that has been linked to autoreactive responses. The purpose of this study was to evaluate the safety, immunogenicity and preliminary efficacy of itolizumab, a humanized anti-CD6 monoclonal antibody, in patients with active rheumatoid arthritis. Fifteen patients were enrolled in a phase I, open-label, dose-finding study. Five cohorts of patients received a weekly antibody monotherapy with a dose-range from 0.1 to 0.8 mg/kg. Itolizumab showed a good safety profile, with no severe or serious adverse events reported so far. No signs or symptoms associated with immunosuppression were observed in the study. Objective clinical responses were achieved in more than 80% of patients after treatment completion, and these responses tend to be sustained afterwards. This clinical study constitutes the first evidence of the safety and positive clinical effect of a monotherapy using an anti-CD6 antibody in patients with rheumatoid arthritis. PMID:24371585

  4. Osteoprotegerin Polymorphisms in a Mexican Population with Rheumatoid Arthritis and Generalized Osteoporosis: A Preliminary Report

    PubMed Central

    Zavala-Cerna, Maria Guadalupe; Moran-Moguel, Maria Cristina; Cornejo-Toledo, Jesus Alejandro; Gonzalez-Montoya, Norma Guadalupe; Sanchez-Corona, Jose; Salazar-Paramo, Mario; Aguilar-Chavez, Erika Anita; Alcaraz-Lopez, Miriam Fabiola; Gonzalez-Sanchez, Alicia Guadalupe

    2015-01-01

    Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. The system formed by receptor activator for nuclear factor-κB (RANK), receptor activator for nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG): RANK/RANKL/OPG is a crucial molecular pathway for coupling between osteoblasts and osteoclasts, since OPG is able to inhibit osteoclast differentiation and activation. We aim to evaluate the association between SNPs C950T (rs2073617), C209T (rs3134069), T245G (rs3134070) in the TNFRSF11B (OPG) gene, and osteoporosis in RA. We included 81 women with RA and 52 healthy subjects in a cross-sectional study, genotyped them, and measured bone mineral density (BMD) at the lumbar spine and the femoral neck. Mean age in RA was 50 ± 12 with disease duration of 12 ± 8 years. According to BMD results, 23 (33.3%) were normal and 46 (66.7%) had osteopenia/osteoporosis. We found a higher prevalence of C allele for C950T SNP in RA. Polymorphisms C209T and T245G did not reach statistical significance in allele distribution. Further studies including patients from other regions of Latin America with a multicenter design to increase the sample size are required to confirm our findings and elucidate if C950T SNP could be associated with osteoporosis in RA. PMID:26065000

  5. Cutaneous abnormalities in rheumatoid arthritis compared with non‐inflammatory rheumatic conditions

    PubMed Central

    Douglas, K M J; Ladoyanni, E; Treharne, G J; Hale, E D; Erb, N; Kitas, G D

    2006-01-01

    Background Cutaneous abnormalities are common in rheumatoid arthritis, but exact prevalence estimates are yet to be established. Some abnormalities may be independent and coincidental, whereas others may relate to rheumatoid arthritis or its treatment. Objectives To determine the exact nature and point prevalence of cutaneous abnormalities in patients with rheumatoid arthritis compared with those in patients with non‐inflammatory rheumatic disease. Methods 349 consecutive outpatients for rheumatology (205 with rheumatoid arthritis and 144 with non‐inflammatory rheumatic conditions) were examined for skin and nail signs by a dermatologist. Histories of rheumatology, dermatology, drugs and allergy were noted in detail. Results Skin abnormalities were reported by more patients with rheumatoid arthritis (61%) than non‐inflammatory controls (47%). More patients with rheumatoid arthritis (39%) than controls (10%) attributed their skin abnormality to drugs. Cutaneous abnormalities observed by the dermatologist were also more common in patients with rheumatoid arthritis (76%) than in the group with non‐inflammatory disease (60%). Specifically, bruising, athlete's foot, scars, rheumatoid nodules and vasculitic lesions were more common in patients with rheumatoid arthritis than in controls. The presence of bruising was predicted only by current steroid use. The presence of any other specific cutaneous abnormalities was not predicted by any of the variables assessed. In the whole group, current steroid use and having rheumatoid arthritis were the only important predictors of having any cutaneous abnormality. Conclusions Self‐reported and observed cutaneous abnormalities are more common in patients with rheumatoid arthritis than in controls with non‐inflammatory disease. These include cutaneous abnormalities related to side effects of drugs or to rheumatoid arthritis itself and other abnormalities previously believed to be independent but which may be of clinical

  6. Comparison of high and low intensity training in well controlled rheumatoid arthritis. Results of a randomised clinical trial.

    PubMed Central

    van den Ende, C H; Hazes, J M; le Cessie, S; Mulder, W J; Belfor, D G; Breedveld, F C; Dijkmans, B A

    1996-01-01

    OBJECTIVE: To investigate the benefit of intensive dynamic exercises in comparison to range of motion (ROM) and isometric exercises in rheumatoid arthritis. METHODS: 100 consecutive rheumatoid arthritis patients on stable medication were randomly assigned to (1) intensive dynamic group exercises which included full weight bearing exercises and conditioning exercises on a stationary bicycle while the heart rate was maintained at 70-85% of the age predicted maximum heart rate, (2) range of motion (ROM) exercises and isometric exercises in a group, (3) individual isometric and ROM exercises, and (4) home instructions for isometric and ROM exercises. Variables of physical condition, muscle strength, joint mobility, daily functioning (HAQ), and disease activity were assessed before and after the 12 week exercise course, and 12 weeks thereafter. An intention to treat analysis was performed. RESULTS: Increases in aerobic capacity (n = 77), muscle strength, and joint mobility in the high intensity exercise programme were respectively 17%, 17% and 16% and differed significantly from the changes in aerobic capacity, muscle strength, and joint mobility in the other exercise groups. No deterioration of disease activity was observed. Twelve weeks after discontinuation of the exercise course the gain in physical capacity had disappeared. CONCLUSIONS: Intensive dynamic training is more effective in increasing aerobic capacity, joint mobility, and muscle strength than ROM exercises and isometric training in rheumatoid arthritis patients with well controlled disease. PMID:8976635

  7. Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene

    PubMed Central

    Rabinovich, E; Livneh, A; Langevitz, P; Brezniak, N; Shinar, E; Pras, M; Shinar, Y

    2005-01-01

    Background: Pyrin is a newly recognised intracellular regulator of inflammation, and mutations in MEFV, the gene encoding pyrin, are the cause of familial Mediterranean fever. Objective: To determine if known mutations of MEFV are associated with rheumatoid arthritis (RA) morbidity or can modify RA severity. Methods: The frequency of the three most common MEFV mutations: M694V, V726A, and E148Q, was determined in 98 Israeli patients with RA (74 women, 24 men) and compared with that in 100 healthy subjects matched for origin. RA severity was determined using a new clinical score of 126 grades. The median severity score of mutation carrier and non-carrier groups was compared after confounding measures were eliminated by logistic regression. Results: 17/98 (17%) patients with RA (all women) were heterozygous for common MEFV mutations, predominantly E148Q (12 patients), and one patient was homozygous for the V726A mutation. The overall mutation rate was comparable between patients with RA and healthy subjects. Patients carrying a mutation had a higher median severity score than the non-carrier group (42 v 29, p = 0.0005). The logistic regression model assigned a 15-fold odds ratio for severe RA in carriers, after adjusting for sex, presence of rheumatoid factor, age at onset, and disease duration (n = 97, p = 0.01, 95% CI 1.74 to 128). Conclusion: MEFV, and particularly the E148Q mutation, is an independent modifier of the clinical manifestations of RA. This is the second Th1-type autoimmune disease in which MEFV mutations have been shown to aggravate the clinical status. PMID:15958759

  8. Rheumatoid Arthritis and Complementary Health Approaches

    MedlinePlus

    ... Davis MC, Reich JW, et al. Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation to rheumatoid arthritis for patients with and without history of recurrent depression. Journal of Consulting and Clinical Psychology . 2008;76(3):408–421. Acupuncture Casimiro L, ...

  9. Pathogenesis of rheumatoid arthritis and the immune response

    SciTech Connect

    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.

  10. Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review

    PubMed Central

    Iqbal, Kundan; Kelly, Clive

    2015-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5–1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease. PMID:26622326

  11. Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review.

    PubMed

    Iqbal, Kundan; Kelly, Clive

    2015-12-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5-1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease. PMID:26622326

  12. High IL-23 level is a marker of disease activity in rheumatoid arthritis.

    PubMed

    Abu Al Fadl, Esam M; Fattouh, Mona; Allam, Ahmed A

    2013-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune systemic disorder characterized by inflammatory responses mainly affecting the synovial joints. Interleukin-23 (IL-23) is a heterodimeric pro-inflammatory cytokine secreted by activated dendritic cells and activated macrophages. IL-23 is the key cytokine controlling inflammation in peripheral tissues leading to the development of autoimmune diseases. The objective of our study was to determine the relationship between the IL-23 level and disease activity in RA patients. Sixty RA patients were included in the study with mean age of 40 years; they included 44 (73.3 %) females and 16 males (26.7 %). The clinical parameters of disease activity were determined, including the 28-joint disease activity score (DAS28), serum levels of C-reactive protein (CRP), Anti-citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and TNF-alpha and the degree of bony erosions based on X-rays. Patients were subdivided into active disease group (n = 30) with DAS28 score higher than 5.1 (Group I); and remission group (n = 30) with DAS28 score less than 2.6 (Group II). Thirty healthy individuals in the same age group of RA patients including 22 (73.3%) females and 8 males (26.7%) were randomly selected as the control group (Group III). The levels of IL-23 were determined by enzyme-linked immunosorbent assay (ELISA) and the correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Serum levels of IL-23 were significantly higher in RA patients during active stage of the disease in comparison to the patients in remission and the control group. There was a significant positive correlation between serum IL-23 levels in RA patients and individual disease activity parameters. It is concluded that elevated serum IL-23 level may be a useful marker to detect active RA and disease progression in patients with RA. PMID:24617049

  13. Interstitial granulomatous dermatitis: rare cutaneous manifestation of rheumatoid arthritis*

    PubMed Central

    Veronez, Isis Suga; Dantas, Fernando Luiz; Valente, Neusa Yuriko; Kakizaki, Priscila; Yasuda, Thaís Helena; Cunha, Thaís do Amaral

    2015-01-01

    Besides being an uncommon clinicopathological entity, interstitial granulomatous dermatitis, also described as interstitial granulomatous dermatitis with arthritis (IGDA), has shown a wide spectrum of clinical manifestations, such as linear and erythematous lesions, papules, plaques and nodules. Histological features include dense dermal histiocytic infiltrate, usually in a palisade configuration, and scattered neutrophils and eosinophils. We describe a middle aged woman with rheumatoid arthritis of difficult management and cutaneous lesions compatible with IGDA. PMID:26131871

  14. Treatment in juvenile rheumatoid arthritis and new treatment options

    PubMed Central

    Kasapçopur, Özgür; Barut, Kenan

    2015-01-01

    Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of the childhood with the highest risk of disability. Active disease persists in the adulthood in a significant portion of children with juvenile rheumatoid arthritis despite many developments in the diagnosis and treatment. Therefore, initiation of efficient treatment in the early period of the disease may provide faster control of the inflammation and prevention of long-term harms. In recent years, treatment options have also increased in children with juvenile idiopathic arthritis owing to biological medications. All biological medications used in children have been produced to target the etiopathogenesis leading to disease including anti-tumor necrosis factor, anti-interleukin 1 and anti-interleukin 6 drugs. In this review, scientific data about biological medications used in the treatment of rheumatoid arthritis and new treatment options will be discussed. PMID:26078691

  15. Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks: a cross-sectional study

    PubMed Central

    2014-01-01

    Introduction Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans. Methods RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model. Results Tissue samples from 58 synovial sites were obtained from 25 patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate Spearman’s ρ = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman’s ρ = 0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.31). IL-6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman’s ρ = 0.50), BME score (P = 0.04, approximate Spearman’s ρ = 0.31) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.35). MIP-1β was associated with CDUS activity (P = 0.02, approximate Spearman’s ρ = 0.38) and RAMRIS synovitis scores (P = 0.02, approximate Spearman’s ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance. Conclusions The association between

  16. Carbamylated vimentin represents a relevant autoantigen in Latin American (Cuban) rheumatoid arthritis patients.

    PubMed

    Martínez, Goitybell; Gómez, Jorge A; Bang, Holger; Martínez-Gamboa, Lorena; Roggenbuck, Dirk; Burmester, Gerd-Rüdiger; Torres, Barbara; Prada, Dinorah; Feist, Eugen

    2016-06-01

    Smoking produces substances that activate proinflammatory, prothrombotic and vasoconstrictive mediators via posttranslational carbamylation of proteins. As a new consequence of carbamylation, induction of anti-carbamylated autoantibodies were observed in rheumatoid arthritis (RA) patients, sometimes prior to onset of the disease. The overall aim of this study was to characterize the reactivity of different isotypes of autoantibodies against carbamylated antigens of vimentin in relation to established rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and markers of disease activity in a so far largely uncharacterized population of Latin American (Cuban) patients with RA. Antigenic properties of carbamylated vimentin as well as vimentin peptides were analyzed in 101 patients with RA, 50 disease controls and 51 healthy controls. The diagnostic performance was compared with established commercial ELISA rheumatoid factor, anti-cyclic citrullinated peptide antibodies of second generation (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies. Prevalence of anti-MCV IgG (86 %), anti-carbamylated vimentin (carbVIM) IgG (77 %) and anti-carbamylated MCV (carbMCV) IgG antibodies (65 %) was higher than the classical RF IgM (60 %) and anti-CCP2 IgG (52 %) in this RA cohort. Of note, smoking status was associated with positive IgG antibody reactivity against CCP2 in 75.0 % and against MCV in 90 % of patients. Furthermore, IgM antibody response against carbMCV and carbVIM was observed in 80 and 90.0 % of smokers, respectively. Due to a high sensitivity of the IgM antibody isotype of anti-carbVIM of 85.2 %, the combination of ACPA with anti-carbVIM IgM provided the best diagnostic performance so far achieved in a RA cohort of this ethnic origin. We demonstrate a high prevalence of anti-carbVIM antibodies and correlation with smoking in Latin American (Cuban) RA patients. Anti-carbVIM IgM represents an useful marker in ACPA

  17. Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden

    PubMed Central

    Frisell, Thomas; Hellgren, Karin; Alfredsson, Lars; Raychaudhuri, Soumya; Klareskog, Lars; Askling, Johan

    2015-01-01

    Objectives Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease. Methods Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register. Results Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives’ other arthritis-related diseases conferred little or no additional risk. Conclusions Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis

  18. The Roles of Cigarette Smoking and the Lung in the Transitions Between Phases of Preclinical Rheumatoid Arthritis.

    PubMed

    Sparks, Jeffrey A; Karlson, Elizabeth W

    2016-03-01

    While the etiology of rheumatoid arthritis (RA) remains to be fully elucidated, recent research has advanced the understanding of RA pathogenesis to the point where clinical trials for RA prevention are underway. The current paradigm for RA pathogenesis is that individuals progress through distinct preclinical phases prior to the onset of clinically apparent RA. These preclinical RA phases consist of genetic risk, local inflammation, presence of RA-related autoantibodies, asymptomatic systemic inflammation, and early non-specific symptoms prior to clinical seropositive RA. Epidemiologic studies have been important in forming hypotheses related to the biology occurring in preclinical RA. Specifically, studies associating cigarette smoking with overall RA risk as well as transitions between phases of preclinical RA were vital in helping to establish the lung as a potential important initiating site in the pathogenesis of seropositive RA. Herein, we review the epidemiology associating smoking with transitions in preclinical phases of RA as well as the recent literature supporting the lung as a critical site in RA pathogenesis. PMID:26951253

  19. CDP-870 (certolizumab) in rheumatoid arthritis.

    PubMed

    Kaushik, V V; Moots, R J

    2005-04-01

    The development of biological anti-TNF-alpha therapy has revolutionised the treatment of rheumatoid arthritis and other inflammatory diseases, and has identified a worldwide market for expensive yet effective therapies for chronic diseases. Certolizumab (CDP-870) is a new agent that employs a novel strategy to neutralise TNF-alpha--namely the prokaryotic expression of TNF-alpha-specific Fab antibody fragments, coupled to polyethylene glycol--to produce a drug that is potentially less expensive to manufacture than other anti-TNF-alpha agents and which may be administered by subcutaneous injection once a month. The background to the ongoing development of this new agent and its clinical effects are discussed in this article. PMID:15934837

  20. The Role of Genetic Variants in CRP in Radiographic Severity in African Americans with Early and Established Rheumatoid Arthritis

    PubMed Central

    Danila, Maria I.; Westfall, Andrew O.; Raman, Krishnan; Chen, Lang; Reynolds, Richard J.; Hughes, Laura B.; Arnett, Donna K.; McGwin, Gerald; Szalai, Alexander J.; van der Heijde, Désirée M.; Conn, Doyt; Callahan, Leigh F.; Moreland, Larry W.; Bridges, S. Louis

    2015-01-01

    This study investigates the association of CRP single nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available in 294 individuals from CLEAR 1 [median (IQR 25-75) disease duration of 1 (0.6-1.6) year] and in 407 persons from CLEAR 2 [median (IQR 25-75) disease duration of 8.9 (3.5 – 17.7) years]. In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score [incident rate ratio (IRR) 0.37 (95% CI 0.19-0.74), p value =0.0051]. In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (p value =0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg/dL when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA. PMID:26226010

  1. Light scattering study of rheumatoid arthritis

    SciTech Connect

    Beuthan, J; Netz, U; Minet, O; Mueller, G; Scheel, A; Henniger, J

    2002-11-30

    The distribution of light scattered by finger joints is studied in the near-IR region. It is shown that variations in the optical parameters of the tissue (scattering coefficient {mu}{sub s}, absorption coefficient {mu}{sub a}, and anisotropy factor g) depend on the presence of the rheumatoid arthritis (RA). At the first stage, the distribution of scattered light was measured in diaphanoscopic experiments. The convolution of a Gaussian error function with the scattering phase function proved to be a good approximation of the data obtained. Then, a new method was developed for the reconstruction of distribution of optical parameters in the finger cross section. Model tests of the quality of this reconstruction method show good results. (laser biology and medicine)

  2. Treg cells in rheumatoid arthritis: an update.

    PubMed

    Cooles, Faye A H; Isaacs, John D; Anderson, Amy E

    2013-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease arising from a breakdown in immunological self-tolerance, which leads to aberrant immune responses to autoantigens. Regulatory CD4(+) T-cells (Tregs) underpin one of the key mechanisms of self-tolerance and are a major focus of study in RA and other autoimmune diseases. In order to design new and improved therapies to reinstate self-tolerance, and perhaps cure disease, we need to understand the complex mechanism of action of Tregs. This review addresses recent findings in the field of Tregs in RA, with particular focus on identification of potential defects in Treg-mediated self-tolerance mechanisms present in RA patients, as well as how Tregs interact with other cells in the inflamed joints. As antigen-specific Tregs are a potential route for the reinstatement of immune tolerance, we also discuss new strategies currently being investigated which expand or induce de novo generation of Tregs. PMID:23888361

  3. 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 ...

  4. A simple algorithm to predict the development of radiological erosions in patients with early rheumatoid arthritis: prospective cohort study.

    PubMed Central

    Brennan, P.; Harrison, B.; Barrett, E.; Chakravarty, K.; Scott, D.; Silman, A.; Symmons, D.

    1996-01-01

    OBJECTIVE: To produce a practical algorithm to predict which patients with early rheumatoid arthritis will develop radiological erosions. DESIGN: Primary care based prospective cohort study. SETTING: All general practices in the Norwich Health Authority, Norfolk. SUBJECTS: 175 patients notified to the Norfolk Arthritis Register were visited by a metrologist soon after they had presented to their general practitioners with inflammatory polyarthritis, and again after a further 12 months. All the patients satisfied the American Rheumatism Association's 1987 criteria for rheumatoid arthritis and were seen by a metrologist within six months of the onset of symptoms. The study population was randomly split into a prediction sample (n = 105) for generating the algorithm and a validation sample (n = 70) for testing it. MAIN OUTCOME MEASURES: Predictor variables measured at baseline included rheumatoid factor status, swelling of specific joint areas, duration of morning stiffness, nodules, disability score, age, sex, and disease duration when the patient first presented. The outcome variable was the presence of radiological erosions in the hands or feet, or both, after 12 months. RESULTS: A simple algorithm based on a combination of three variables--a positive rheumatoid factor test, swelling of at least two large joints, and a disease duration of more than three months--was best able to predict erosions. When the accuracy of this algorithm was tested with the validation sample, the erosion status of 79% of patients was predicted correctly. CONCLUSIONS: A simple algorithm based on three easily measured items of information can predict which patients are at high risk and which are at low risk of developing radiological erosions. PMID:8776318

  5. Gene Polymorphisms and Pharmacogenetics in Rheumatoid Arthritis

    PubMed Central

    Rego-Pérez, Ignacio; Fernández-Moreno, Mercedes; Blanco, Francisco J

    2008-01-01

    Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient’s genetic profile. PMID:19506728

  6. [Tofacitinib for the treatment of rheumatoid arthritis].

    PubMed

    Tanaka, Yoshiya

    2016-06-01

    The combined use of synthetic disease-modifying anti-rheumatic drugs (sDMARDs) such as methotrexate and biological DMARDs (bDMARDs) has revolutionized treatment of rheumatoid arthritis (RA). Remission is now realistic targets, achieved by a large proportion of RA patients. However, bDMARDs are limited to intravenous or subcutaneous uses and orally available small but strong products have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active RA patients with sDMARD-naïve, inadequately responsive to sDMARDs or TNF-inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. The common adverse events were related to infection, hematologic and hepatic disorders and association of tofacitinib with carcinogenicity and infections remains debated. PMID:27311188

  7. [Auriculo-electropuncture in rheumatoid arthritis (a double-blind study)].

    PubMed

    Ruchkin, I N; Burdeĭnyĭ, A P

    1987-01-01

    A study of the efficacy of auriculo-electropuncture (AEP) by a double blind method was conducted in 16 patients with rheumatoid arthritis (RA). Points on the auricle were looked for by means of an device of individual use. After that during true AEP (the study group of 10 patients) the device was switched on to the stimulation mode, during false AEP (the control group of 6 patients) it was switched off. Each patient was given 10 procedures except one patient of the study group in whom treatment had to be discontinued after the 3rd procedure because of the development of phlebitis of the left crural veins. Subjective assessment showed improvement in all the patients of the study group (considerable improvement in 2 patients), in the control group improvement was noted in one patient only, no effect--in 3 patients, deterioration--in 2 patients; objective assessment showed improvement in 6 (considerable improvement in one patient) and in one patient, no effect--in 2 and 2, deterioration in one and 3, respectively. In the study group a positive time course of all 8 indices characterizing a degree of pain and inflammatory activity was noted (it was statistically significant for 7 of them), in the control group a positive time course of 3 indices was noted, 5 indices grew worse. A statistically significant decrease in the initially elevated level of blood alpha (2)-globulin was noted against a background of true AEP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3328905

  8. Solid Lipid Nanoparticles: A Potential Multifunctional Approach towards Rheumatoid Arthritis Theranostics.

    PubMed

    Albuquerque, João; Moura, Catarina Costa; Sarmento, Bruno; Reis, Salette

    2015-01-01

    Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN), a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA. Methotrexate (MTX) and superparamagnetic iron oxide nanoparticles (SPIONs) were co-encapsulated inside the SLNs to be used as therapeutic and imaging agents, respectively. All the formulations presented sizes under 250 nm and zeta potential values lower than -16 mV, suitable characteristics for intravenous administration. Transmission electron microscopy (TEM) photographs indicated that the SPIONs were encapsulated inside the SLN matrix and MTX association efficiency values were higher than 98%. In vitro studies, using THP-1 cells, demonstrated that all formulations presented low cytotoxicity at concentrations lower than 500 μg/mL. It was proven that the proposed NPs were not cytotoxic, that both a therapeutic and imaging agent could be co-encapsulated and that the SLN could be functionalized for a potential future application such as anti-body specific targeting. The proposed formulations are, therefore, promising candidates for future theranostic applications. PMID:26087258

  9. Patient-initiated appointments compared with standard outpatient care for rheumatoid arthritis: a randomised controlled trial

    PubMed Central

    Fredriksson, Cecilia; Ebbevi, David; Waldheim, Eva; Lindblad, Staffan; Ernestam, Sofia

    2016-01-01

    Objectives To test the hypothesis that implementing a patient-initiated system of care could improve clinical outcome in rheumatoid arthritis (RA) using disease activity guided management. Methods An 18-month controlled blinded end point two-centre study with 131 patients with RA randomised to intervention (n=64) or control (n=67). The intervention group participants were guaranteed appointments to a rheumatologist within 10 working days if they subjectively experienced a flare in disease activity. The control group participants were booked in advance according to guidelines. Independent assessments were performed in the two groups at 0, 3, 6, 12 and 18 months. Outcome measures included: Disease Activity Score 28 (DAS28), a Visual Analogue Scale (satisfaction with care, confidence in care), number of appointments with a rheumatologist. Results DAS28 decreased. Median satisfaction and confidence in care were >90 mm on Visual Analog Scale. Median number of appointments was 3. There were no significant differences between the groups among these outcomes. Visits in the intervention group more often resulted in change of treatment than in the control group (p<0.001). Conclusions Patient-initiated care was neither better nor inferior to traditional care in terms of outcomes analysed. Patient-initiated appointments can safely be used in everyday outpatient care of RA to empower the patient, if disease activity guided management is applied. Further research should investigate if this intervention can target a subgroup of patients and hence also result in released resources. PMID:27042334

  10. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update

    PubMed Central

    Stoffer, Michaela A; Schoels, Monika M; Smolen, Josef S; Aletaha, Daniel; Breedveld, Ferdinand C; Burmester, Gerd; Bykerk, Vivian; Dougados, Maxime; Emery, Paul; Haraoui, Boulos; Gomez-Reino, Juan; Kvien, Tore K; Nash, Peter; Navarro-Compán, Victoria; Scholte-Voshaar, Marieke; van Vollenhoven, Ronald; Stamm, Tanja A

    2016-01-01

    Objective A systematic literature review (SLR; 2009–2014) to compare a target-oriented approach with routine management in the treatment of rheumatoid arthritis (RA) to allow an update of the treat-to-target recommendations. Methods Two SLRs focused on clinical trials employing a treatment approach targeting a specific clinical outcome were performed. In addition to testing clinical, functional and/or structural changes as endpoints, comorbidities, cardiovascular risk, work productivity and education as well as patient self-assessment were investigated. The searches covered MEDLINE, EMBASE, Cochrane databases and Clinicaltrial.gov for the period between 2009 and 2012 and separately for the period of 2012 to May of 2014. Results Of 8442 citations retrieved in the two SLRs, 176 articles underwent full-text review. According to predefined inclusion/exclusion criteria, six articles were included of which five showed superiority of a targeted treatment approach aiming at least at low-disease activity versus routine care; in addition, publications providing supportive evidence were also incorporated that aside from expanding the evidence provided by the above six publications allowed concluding that a target-oriented approach leads to less comorbidities and cardiovascular risk and better work productivity than conventional care. Conclusions The current study expands the evidence that targeting low-disease activity or remission in the management of RA conveys better outcomes than routine care. PMID:25990290

  11. Rheumatoid arthritis, a complex multifactorial disease: on the way toward individualized medicine.

    PubMed

    Glocker, Michael O; Guthke, Reinhard; Kekow, Jörn; Thiesen, Hans-Jürgen

    2006-01-01

    With the availability of the human genome sequence and those of related species like chimpanzee, mouse, and rat, data driven research for tackling the molecular grounds of rheumatoid arthritis (RA), a multifactorial polygenic disease, can be considered a realistic challenge to the scientific community. A comprehensive research strategy is presented enabling the integration of multiple research efforts on studying autoimmunity by so called systems biology approaches. An integrative scientific concept is discussed of how to unravel molecular mechanisms of complex diseases by making use of state-of-the-art methodologies in functional and comparative genomics. A continuous interchange of data-driven and hypothesis-driven research is adjoined to determine the nature of rheumatic diseases with autoimmune background. Instead of studying single genes and proteins, RNA and protein microarray profiles are currently obtained in numerous research projects producing read-outs termed gene signatures rather than DNA and/or protein markers. A comprehensive study of the RNA, protein, and metabolite regimes is undertaken that eventually will lead to a "holistic" view of how all respective molecules, pathways and cells themselves interact with each other. Some of the above mentioned research aspects have already been studied by the authors, hopefully leading to new diagnostics and therapeutics in the future. PMID:16283676

  12. Methotrexate, Cyclosporine A, and Biologics Protect against Atherosclerosis in Rheumatoid Arthritis

    PubMed Central

    Kruszewski, Robert; Juszkiewicz, Aleksandra; Raczkiewicz, Anna; Bachta, Artur; Tłustochowicz, Małgorzata; Staniszewska-Varga, Jadwiga; Kłos, Krzysztof; Duda, Krzysztof; Bogusławska-Walecka, Romana; Płoski, Rafał; Tłustochowicz, Witold

    2015-01-01

    Introduction. The risk of cardiovascular disease is increased in rheumatoid arthritis (RA). A meta-analysis showed increased intima media thickness (IMT) in RA. It has been shown that disease modifying antirheumatic drugs (DMARDs) may influence the progression of atherosclerosis. However, it was suggested that biologics may be more efficient than other DMARDs (including methotrexate—MTX) in protecting against atherosclerosis. Objectives. The aim of this study was to assess the influence of different RA characteristics and treatment regimens on IMT and atherosclerotic plaques. Patients and Methods. 317 RA patients and 111 controls were included in the study. IMT was measured in carotid (CIMT) and femoral (FIMT) arteries. Arteries were screened for the presence of plaques. Results. CIMT, FIMT, and prevalence of plaques were lower in patients treated with methotrexate (MTX) ≥ 20 mg/wk, cyclosporine (CsA), or biologics than in patients treated with lower doses of MTX and other disease modifying antirheumatic drugs. No differences in IMT between patients treated with MTX ≥ 20 mg/wk, biologics, or CsA were found. Conclusions. We found a beneficial effect of MTX ≥ 20 mg/wk, biologics, and CsA on atherosclerosis. We do not confirm a stronger influence of biologics on IMT compared with therapeutic doses of MTX. PMID:26090499

  13. What predicts negative effects of rheumatoid arthritis? A follow-up two years after diagnosis.

    PubMed

    Gåfvels, Catharina; Hägerström, Margareta; Nordmark, Birgitta; Wändell, Per

    2014-01-01

    We aimed at analyzing important predictive factors for experienced negative emotional and social effects of rheumatoid arthritis (RA) two years after diagnosis in patients aged 18-65 years. The first group included 41 participants, who had psychosocial problems (PSP) already at diagnosis, and who received an intervention by a medical social worker to improve coping capacity and social situation. The second group included 54 patients (NPSP) without such problems at diagnosis. All completed a questionnaire mapping their social situation, the Hospital Anxiety and Depression Scale (HADS), the Sense of Coherence Scale (SOC) and the General Coping Questionnaire (GCQ) at diagnosis and after 24 months. The most pronounced predictive factor for a strong impact of the disease was high scores on HADS depression scale. After 24 months, PSP participants had a more strained life situation, with higher scores on anxiety and depression and lower on SOC, in comparison with NPSP. NPSP participants improved their coping strategies regarding self-trust, cognitive revaluation, protest and intrusion, but deteriorated regarding problem focusing and social trust. PSP patients kept their initial coping strategies, except for intrusion decreasing over time, and seemed to have a more rigid coping pattern. However, the experienced negative impact of the disease increased over time in both groups despite improvement in sickness related data. Mostly influenced areas were economy, leisure time activities and social life. We conclude that psychosocial consequences of RA are more connected to emotional and social vulnerability than are RA-related clinical factors. PMID:24634809

  14. [Rituximab (MabThera)--a new biological medicine in rheumatoid arthritis therapy].

    PubMed

    Nemec, P

    2007-11-01

    Rheumatoid arthritis (RA) is a serious, chronic, inflammatory disorder that damages the joints. The chronic destructive process causes pain to patients with RA and leads to the development of permanent disability. At present, great emphasis is placed on timely and effective therapy for RA, which is able to halt or slow the development of the disorder. At present we do not have any means of curing RA, the main objective for treatment is to induce remission of the disorder and prevent structural damage to the joints and the development of permanent disability. The relatively frequent failure of disease modifying medications (DMARDs) lead to efforts to find new resources for the treatment of RA. So called biological medicines were recently introduced into therapeutic use. These were mainly TNFalpha blockers. Experience has shown that approximately a third of patients with RA do not respond even to treatment with such medicines. Rituximab (MabThera), a monoclonal antibody against CD20 positive B-lymphocytes, is a new biological medicine approved for RA therapy. It represents a new hope for patients with active RA, for whom earlier therapy with TNFa blockers has failed. PMID:18277630

  15. Genetics of rheumatoid arthritis: a new boost is needed in Latin American populations.

    PubMed

    Castro-Santos, Patricia; Díaz-Peña, Roberto

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory rheumatic disease which affects several organs and tissue, predominantly the synovial joints. Like many other autoimmune diseases, RA is a complex disease, where genetic variants, environmental factors and random events interact to trigger pathological pathways. Genetic implication in RA is evident, and recent advances have expanded our knowledge about the genetic factors that contribute to RA. An exponential increment in the number of genes associated with the disease has been described, mainly through gene wide screen studies (GWAS) involving international consortia with large patient cohorts. However, there are a few studies on Latin American populations. This article describes what is known about the RA genetics, the future that is emerging, and how this will develop a more personalized approach for the treatment of the disease. Latin American RA patients cannot be excluded from this final aim, and a higher collaboration with the international consortia may be needed for a better knowledge of the genetic profile of patients from this origin. PMID:27267531

  16. Effect of yogic package on rheumatoid arthritis.

    PubMed

    Singh, Vijay Kumar; Bhandari, R B; Rana, Budhi Bal

    2011-01-01

    This study aimed at studying the effect of yogic package (YP) with some selected pranayama, cleansing practices and meditation on pain intensity, inflammation, stiffness, pulse rate (PR), blood pressure (BP), lymphocyte count (LC), C-reactive protein (CRP) and serum uric acid (UA) level among subjects of rheumatoid arthritis (RA). Randomized control group design was employed to generate pre and post data on participants and controls. Repealed Measure ANOVAs with Bonferroni adjustment were applied to check significant overall difference among pre and post means of participants and controls by using PASW (SPSS Inc. 18th Version). Observed result favored statistically significant positive effect of YP on selected RA parameters and symptoms under study at P<0.05, 0.01 and 0.001 respectively that showed remarkable improvement in RA severity after 40-day practice of YP. It concluded that YP is a significant means to reduce intensity of RA. PMID:23362725

  17. Coexistence of rheumatoid arthritis and ankylosing spondylitis

    PubMed Central

    Węgierska, Małgorzata; Żuchowski, Paweł; Dura, Marta; Zalewska, Joanna; Waszczak, Marzena; Jeka, Sławomir

    2015-01-01

    Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic progressive inflammatory diseases, leading to joint damage and reducing the physical fitness of patients. They are among the most common rheumatic diseases. However, their etiology and symptomatology are different. Formerly, AS was often wrongly diagnosed as RA. Today there are no major diagnostic difficulties in differentiation between these diseases, thanks to modern laboratory tests and imaging. However, a problem may arise when the patient has symptoms typical for both diseases simultaneously. Cases of coexistence of RA with AS – according to our best knowledge – are rare. This study aims to compare our experience in diagnosis and treatment of concomitant RA and AS with the experience of other researchers. Implementation of the proper diagnostic algorithm, allowing for correct diagnosis of both diseases in one patient, may be useful for differential diagnosis of similar cases in the future.

  18. Determinants of Disability in Rheumatoid Arthritis: A Community-Based Cohort Study

    PubMed Central

    Krause, Megan L.; Crowson, Cynthia S.; Bongartz, Tim; Matteson, Eric L.; Michet, Clement J.; Mason, Thomas G.; Persellin, Scott T.; Gabriel, Sherine E.; Davis, John M.

    2015-01-01

    Longitudinal care of a community-based cohort of patients with rheumatoid arthritis (RA) was evaluated retrospectively. Candidate determinants of disability included visual analog scales (VAS) for patient global assessment and pain, comorbidities, and medications. The outcome was the ‘patient-acceptable symptom state’ for disability as defined by the Health Assessment Questionnaire (HAQ) disability index, using a cutoff of <1.04. Two-sample t tests and multivariable logistic regression were used to determine odds ratios (OR) for associations between predictor variables and disability. Out of a total of 99 patients, 28 (28%) patients had HAQ ≥1.04 at their last visit. The greatest odds of not attaining the patient-acceptable symptom state in a multivariable model was associated with corticosteroids (OR: 5.1; p=0.02), antidepressants (OR: 5.3; p=0.02), and female sex (OR: 6.5; p=0.05). In the era of biologic therapy, female sex, corticosteroids, and antidepressants remain profound determinants of disability highlighting the need to understand the underlying mechanisms. PMID:26862353

  19. Deficient cytokine control modulates temporomandibular joint pain in rheumatoid arthritis.

    PubMed

    Ahmed, Neveen; Catrina, Anca I; Alyamani, Ahmed O; Mustafa, Hamid; Alstergren, Per

    2015-08-01

    The aim was to investigate how endogenous cytokine control of tumor necrosis factor (TNF) influences temporomandibular joint (TMJ) pain in relation to the role of anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA). Twenty-six consecutive patients with TMJ RA were included. Temporomandibular joint pain intensity was assessed at rest, on maximum mouth opening, on chewing, and on palpation. Mandibular movement capacity and degree of anterior open bite (a clinical sign of structural destruction of TMJ tissues) were also assessed. Systemic inflammatory activity was assessed using the Disease Activity Score in 28 joints (DAS28) for rheumatoid arthritis. Samples of TMJ synovial fluid and blood were obtained and analyzed for TNF, its soluble receptor, soluble TNF receptor II (TNFsRII), and ACPA. A high concentration of TNF in relation to the concentration of TNFsRII in TMJ synovial fluid was associated with TMJ pain on posterior palpation on maximum mouth opening. The ACPA concentration correlated significantly to the TNF concentration, but not to the TNFsRII concentration, indicating that increased inflammatory activity is mainly caused by an insufficient increase in anti-inflammatory mediators. This study indicates that TMJ pain on palpation in patients with RA is related to a deficiency in local cytokine control that contributes to increased inflammatory activity, including sensitization to mechanical stimuli over the TMJ. PMID:26010823

  20. Understanding the diverse functions of Huatan Tongluo Fang on rheumatoid arthritis from a pharmacological perspective

    PubMed Central

    ZHENG, CHUNSONG; QIU, MINGSHAN; XU, XIAOJIE; YE, HONGZHI; ZHANG, QIAN; LI, YIHAN; LIU, XIANXIANG; CHEN, JINCHUN

    2016-01-01

    Huatan Tongluo Fang (HTTLF) is a traditional herbal formula that can resolve phlegm and dredge collaterals. HTTLF has also been used to treat rheumatoid arthritis (RA); however, the mechanism underlying the therapeutic effects of HTTLF on RA has not been clearly elucidated at the molecular level. In the present study, an integrated model of system pharmacology containing chemical space analysis, potential active compound prediction and compound-target-disease network was constructed to investigate the molecular mechanisms of HTTLF. The compounds from HTTLF dispersed well in the chemical space. Most of the compounds from HTTLF had similar chemical spaces to drug/drug-like compounds associated with RA, according to the MDL Drug Data Report. A total of 127 potentially active compounds and 17 targets of RA were identified. Among them, 50 compounds interacted with ≥2 targets, while 77 compounds interacted with only one target. In addition, 17 targets were associated with 82 diseases that belonged to 26 categories. These results indicate that HTTLF has diverse chemical spaces and polypharmacology with regards to the treatment of RA. In addition, HTTLF demonstrated therapeutic potential against diverse diseases other than RA, including osteoarthritis, atherosclerosis and brain cancer. This study provides a novel platform for understanding how HTTLF treats RA; this is beneficial for explaining the diverse functions of HTTLF with regards to RA, and may help develop novel compounds with desirable therapeutic targets to treat RA. PMID:27347021

  1. 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.

  2. Glucocorticoid-Responsive Cold Agglutinin Disease in a Patient with Rheumatoid Arthritis.

    PubMed

    Honne, Kyoko; Nagashima, Takao; Iwamoto, Masahiro; Kamesaki, Toyomi; Minota, Seiji

    2015-01-01

    A 57-year-old man with rheumatoid arthritis developed severe anemia during treatment with adalimumab plus methotrexate. Cold agglutinin disease was diagnosed because haptoglobin was undetectable, cold agglutinin was positive (1 : 2048), and the direct Coombs test was positive (only to complement). Although the cold agglutinin titer was normalized (1 : 64) after treatment with prednisolone (0.7 mg/kg/day for two weeks), the patient's hemoglobin did not increase above 8 g/dL. When cold agglutinins were reexamined using red blood cells suspended in bovine serum albumin, the titer was still positive at 1 : 1024. Furthermore, the cold agglutinin had a wide thermal amplitude, since the titer was 1 : 16 at 30°C and 1 : 1 at 37°C. This suggested that the cold agglutinin would show pathogenicity even at body temperature. After the dose of prednisolone was increased to 1 mg/kg/day, the patient's hemoglobin rapidly returned to the normal range. The thermal amplitude test using red blood cells suspended in bovine serum albumin is more sensitive than the standard test for detecting pathogenic cold agglutinins. PMID:26346552

  3. Efficacy of total lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized trial

    SciTech Connect

    Strober, S.; Tanay, A.; Field, E.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.; Brown, B.W.; Kaplan, H.S.

    1985-04-01

    Twenty-six patients participated in a randomized, double-blind study of the efficacy of total lymphoid irradiation in the treatment of intractable rheumatoid arthritis. All 26 patients, for whom therapy with gold compounds and penicillamine had failed, would ordinarily have been considered candidates for cytotoxic or antimetabolite drug therapy. Thirteen patients randomly assigned to receive full-dose total lymphoid irradiation (2000 rad) and 11 patients assigned to receive control low-dose total lymphoid irradiation (200 rad) completed radiotherapy. Alleviation of joint disease activity was significantly greater in the high-dose group as judged by morning stiffness, joint tenderness, and functional assessment (global composite score) at 3 and 6 months after radiotherapy. The high-dose group had a marked reduction in both T-lymphocyte function and numbers, but this finding was not observed in the low-dose group. Complications seen in the high-dose but not low-dose group included transient neutropenia, thrombocytopenia, pericarditis, and pleurisy.

  4. Benefit and Risk of Tofacitinib in the Treatment of Rheumatoid Arthritis: A Focus on Herpes Zoster.

    PubMed

    Yamaoka, Kunihiro

    2016-09-01

    The biologics have revolutionized the treatment of rheumatoid arthritis (RA). However, there are still patients that are difficult to control and a cure is still not achievable. Tofacitinib, a Janus kinase (JAK) inhibitor is an orally available, new-in-class, disease-modifying anti-rheumatic drug with similar efficacy to biologics. JAK is activated by multiple cytokines involved in the pathology of RA, and affects non-immune and immune cells, mainly the lymphocytes. Besides its anti-rheumatic effect, the recent focus has been on adverse events. As with other biologics, serious infections have been observed especially with patients with lymphopenia, consistent with the mechanism of action. The major difference in adverse events from other disease-modifying anti-rheumatic drugs is the prominent increase in the occurrence of herpes zoster; it is increased worldwide, especially in Asia. There are other concerns such as malignancies and hyperlipidemia that may cause cardiovascular events that deserve further attention. The first JAK inhibitor for RA is demonstrating great benefit along with some risk, providing insights into the post-biologic era. PMID:27193610

  5. Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis

    SciTech Connect

    Kawahito, Yutaka; Ichinose, Sizuko; Sano, Hajime; Tsubouchi, Yasunori; Kohno, Masataka; Yoshikawa, Toshikazu; Tokunaga, Daisaku; Hojo, Tatsuya; Harasawa, Ryo; Nakano, Teruaki; Matsuda, Kazuhiro

    2008-05-02

    Mycoplasma fermentans has been suspected as one of the causative pathogenic microorganisms of rheumatoid arthritis (RA) however, the pathogenic mechanism is still unclear. We, previously, reported that glycolipid-antigens (GGPL-I and III) are the major antigens of M. fermentans. Monoclonal antibody against the GGPL-III could detect the existence of the GGPL-III antigens in synovial tissues from RA patients. GGPL-III antigens were detected in 38.1% (32/84) of RA patient's tissues, but not in osteoarthritis (OA) and normal synovial tissues. Immunoelectron microscopy revealed that a part of GGPL-III antigens are located at endoplasmic reticulum. GGPL-III significantly induced TNF-{alpha} and IL-6 production from peripheral blood mononulear cells, and also proliferation of synovial fibroblasts. Further study is necessary to prove that M. fermentans is a causative microorganism of RA; however, the new mechanisms of disease pathogenesis provides hope for the development of effective and safe immunotherapeutic strategies based on the lipid-antigen, GGPL-III, in the near future.

  6. Multifocal inflammatory demyelination in a patient with rheumatoid arthritis and treatment complications.

    PubMed

    Lu, Jian-Qiang; Ringrose, Jennifer; Gross, Donald; Emery, Derek; Blevins, Gregg; Power, Christopher

    2016-08-15

    Rheumatoid arthritis (RA) and multiple sclerosis (MS) are both autoimmune diseases that share similar pathogenesis, but the development of MS in RA patients without the treatment of anti-tumor necrosis factor-alpha is rarely reported, which might be attributed to the use of other medications with potential immunosuppressive effects in the treatment of RA. Since MS can be clinically silent and autopsy examination of the central nervous system in RA patients is rarely described, the association of MS with RA may be possibly under-recognized. We report an autopsy case revealing multifocal inflammatory demyelination in a RA patient who had a prolonged use of methotrexate and hydroxychloroquine resulting in hydroxychloroquine-induced myopathies and heart failure. The neuropathological features of this case are consistent with MS, although there are some altered inflammatory demyelinating features such as relatively smaller lesions and less infiltration of inflammatory cells, particularly T-cells. Our present case, in combination with literature review, suggests that the RA treatment especially with hydroxychloroquine and methotrexate is likely to alter the characteristics of inflammatory demyelination and disease course. PMID:27423608

  7. Bidirectional associations between rheumatoid arthritis and depression: a nationwide longitudinal study

    PubMed Central

    Lu, Ming-Chi; Guo, How-Ran; Lin, Miao-Chiu; Livneh, Hanoch; Lai, Ning-Sheng; Tsai, Tzung-Yi

    2016-01-01

    Rheumatoid arthritis (RA) and depression may be associated with each other pathophysiologically, but few studies have been conducted on the interplay between these two diseases using longitudinal measurement. Therefore, we used the National Health Insurance Research Database of Taiwan to investigate the bidirectional associations between RA and depression. One cohort was included to analyze RA predicting the onset of depression and a second cohort for analysis of depression predicting RA. A sex- and age-matched control group was included for both. The incidence of depression in RA subjects was higher than in non-RA subjects [15.69 vs. 8.95 per 1,000 person-years (PYs)], with an adjusted hazard ratios (HRs) of 1.69 [95% confidence interval (CI), 1.51–1.87]. The incidence of RA was higher in depressed than non-depressed individuals (2.07 vs. 1.21 per 1,000 PYs), with an adjusted HRs of 1.65 (95% CI, 1.41–1.77). This population-based cohort study suggested strong bidirectional relationships between RA and depression. Healthcare providers are recommended to facilitate the implementation of more effective therapeutic interventions to achieve favorable prognosis, especially for those with new-onset or younger cases. PMID:26857028

  8. Clinical Significance of Auditive Involvement in Rheumatoid Arthritis: A Case-Control Study

    PubMed Central

    Alonso, Laura; Gutierrez-Farfan, Ileana; Peña-Ayala, Angelica; Perez-Bastidas, Maria-Esther; Espinosa, Rolando

    2011-01-01

    Introduction. Rheumatoid arthritis (RA) can involve the incudomalleolar or incudostapedial articulations. Objective. To know the punctual prevalence of audiological alterations in patients with RA. Patients and Methods. RA patients and their controls (Cs), were evaluated by Tonal Audiometry (AU); if there were alterations in the air conduction (AC), bone conduction (BC), Logoaudiometry (LG), and Tympanometry (T) were performed. Results. 45 RA patients and 45 Cs were evaluated. RA patients had 40% of bilateral and 17.8% unilateral alteration versus Cs with 22.2% bilateral and 4.4% unilateral alteration versus Cs with 22.2% bilateral and 4.4% unilateral in AC audiometry. In conventional T (CT) As-type curves in patients with RA, there were 22 LE (48.8%) and 26 RE (57.7%) versus Cs, there were16 RE (35.5%) and 20 LE (44.4%). In High-frequency T (HFT): the 3B1G pattern in RA more frequent versus Controls (Cs) in RE (P = .002 and LE (P = .01). There were no differences according to RA activity or RA disease evolution. Conclusions. There is a greater tendency of auditive loss of As curves in CT (rigidity in ossicular chain) and of the 3B1G pattern in HFT in RA. PMID:22482066

  9. Adherence to Methotrexate therapy in Rheumatoid Arthritis

    PubMed Central

    Arshad, Nasim; Ahmad, Nighat Mir; Saeed, Muhammad Ahmed; Khan, Saira; Batool, Shabnam; Farman, Sumaira

    2016-01-01

    Objective: To determine adherence to methotrexate (MTX) therapy in patients with Rheumatoid Arthritis (RA) and to identify factors that promote either adherence or non adherence. Methods: One hundred Rheumatoid Arthritis patients on MTX for at least two months were enrolled. Questionnaire was completed by direct interview. Details recorded were, demographics (age, sex, education, monthly income), disease duration, duration on MTX and current dose. Disease Activity Score on 28 joint counts (DAS 28) at the current visit, concomitant drugs taken and number of doses of MTX missed in the previous 8 weeks were noted. Non adherence was defined as omission of any three or more prescribed doses of MTX in previous 8 week. Patients were asked for the factors that motivated their adherence to MTX as well as factors for non adherence. Presence of side effects due to MTX was also recorded. Result: Non adherence was found among 23% of cases. Patients of low socioeconomic group (p <0.0001) and on MTX for longer duration (p <0.001) had higher non adherence. Non adherent patients had significantly higher disease activity as measured by DAS 28 (p<0.001). Good counseling and education by the doctor was a strong predictor of adherence (p <0.001). Lack of affordability (p <0.001); lack of availability at local pharmacy (p <0.001); lack of family support (p <0.001) and lack of awareness regarding need and importance of MTX (p < 0.001were found as significant factors for non adherence. Conclusion: MTX non adherence in RA is noted in about one fourth of study group. Various economical and social issues lead to non adherence but good patient education and counseling by doctor could promote adherence in this study group. PMID:27182251

  10. Comorbidity profile among patients with rheumatoid arthritis and the impact on prescriptions trend.

    PubMed

    Al-Bishri, J; Attar, Sm; Bassuni, Nawal; Al-Nofaiey, Yasser; Qutbuddeen, Hamed; Al-Harthi, Salma; Subahi, Sarah

    2013-01-01

    Comorbid conditions play a pivotal role in rheumatoid arthritis management and outcomes. We estimated the percentage of comorbid illness among rheumatoid arthritis patients and explored the relationship between this comorbidity and different prescriptions. A cross-sectional study of patients with rheumatoid arthritis in three centers in Saudi Arabia was carried out. Comorbidity and antirheumatoid medication regimens prescribed were recorded on a specially designed Performa. The association between comorbidity and different drugs was analyzed. A total of 340 patients were included. The most comorbidities were hypertension 122 (35.9%), diabetes 105 (30.9%), osteoporosis 88 (25.8%), and dyslipidemia in 66 (19.4). The most common drug prescribed was prednisolone in 275 (80.8%) patients followed by methotrexate in 253 (74.4%) and biological therapy in 142 (41.5%) patients. Glucocorticoids were prescribed considerably more frequently in hypertensive and diabetic patients as well as in patients with osteoporosis and dyslipidemia. Most patients with rheumatoid arthritis suffered from comorbid diseases. PMID:23645988

  11. [Biologics as first line therapy in the treatment of rheumatoid arthritis. A posture a favor].

    PubMed

    Hernández Cruz, Blanca

    2009-04-01

    Changes in diagnosis and treatment of rheumatoid arthritis oblige us to question clinical practice. Evidence demonstrates that the combination of biologics and methotrexate in rapid increments leads to larger remission rates than methotrexate alone. The combination has a faster clinical response in activity, physical function, quality of life, fatigue and sleep. But the most significant effect of biologics is on radiographic progression. The reduction in radiological damage has a spectrum that goes from anti-TNF+methotrexate to anti-TNF monotherapy, being less with methotrexate, and independent from improvement in activity; it occurs with all of the anti-TNF drugs and with other targets with different mechanisms of action (anti-CD20, T cell costimulation inhibitors and anti IL-6). The clinical significance of this finding will be seen in the future, when more is known of its impact on the poor outcomes of RA patients. Because methotrexate is an excellent drug, it seems madness to say that all patients should receive biologics+methotrexate, but it is reasonable to consider that a subgroup must receive them from the start. The American College of Rheumatology recommends their use in patients with RA of less than 6 months since onset, with no previous exposure to methotrexate, persistent and elevated activity (<3 months) and poor prognostic factors or those with persistent and elevated activity (3-6 months) independent of poor prognostic factors, and if the patient "has insurance". A final thought would be: Is there a new treatment pyramid which has cost at its base now? PMID:21794638

  12. A strategy for reaching therapeutic salicylate levels in patients with rheumatoid arthritis using standardized dosing regimens.

    PubMed

    Furst, D E; Blocka, K; Cassell, S; Dromgoole, S; Harris, E R; Hirschberg, J M; Josephson, N; Rupp, P A; Paulus, H E; Trimble, R B

    1987-04-01

    After one to 2 weeks of 45 mg/kg/day choline magnesium trisalicylate (CMT) in 2 divided doses, 51 of 71 patients with rheumatoid arthritis (72%) had observed steady state serum salicylate concentrations between 150 and 300 mg/l (mean salicylate: 213 +/- 10 mg/l), although 17 later required dose adjustment. CMT dosing was changed in 37 cases by using the formula: dosing rate = total clearance X concentration. The expected and observed concentrations were not different (p = 0.31); thus, this formula can help calculate salicylate dosing changes to bring the serum salicylate level to within the therapeutic range. PMID:3599003

  13. Spontaneous establishment of an Epstein-Barr virus-infected fibroblast line from the synovial tissue of a rheumatoid arthritis patient.

    PubMed Central

    Koide, J; Takada, K; Sugiura, M; Sekine, H; Ito, T; Saito, K; Mori, S; Takeuchi, T; Uchida, S; Abe, T

    1997-01-01

    An Epstein-Barr virus (EBV)-infected fibroblast line, designated DSEK, was spontaneously established from synovial tissue of a patient with rheumatoid arthritis (RA). DSEK cells expressed EBV nuclear antigens EBNA-1 and EBNA-2 and latent membrane protein LMP-1. Cell surface markers of DSEK cells were similar to those of EBV-negative fibroblast clones derived from synoviocytes and were negative for lymphocyte and macrophage markers. DSEK cells expressed CD44, CD58, and HLA-DR antigens and spontaneously produced interleukin-10 basic fibroblast growth factor and transforming growth factor beta1. These results indicate that rheumatoid synoviocytes can be a target for EBV infection and suggest that EBV may play a role in the pathogenesis of RA. PMID:9032386

  14. 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

  15. 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. PMID:3977410

  16. Total glucosides of paeony for rheumatoid arthritis: a protocol for a systematic review

    PubMed Central

    Luo, Jing; Jin, Di-Er; Yang, Guo-Yan; Zhang, Ying-Ze; Wang, Jian-Ming; Kong, Wei-Ping; Tao, Qing-Wen

    2016-01-01

    Introduction Total glucosides of paeony (TGP) is a natural plant extract, which is widely used in China for treating rheumatoid arthritis (RA). Many relevant randomised controlled trials (RCTs) of TGP for RA are available, but they have not been systematically reviewed. This systematic review aims to examine the effectiveness and safety of TGP in patients with RA. Methods and analyses We will search for RCTs of TGP in the treatment of RA, performed up until February 2016, in PubMed, Embase, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database). Trial registers and reference lists of retrieved articles will also be searched to identify potential articles. RCTs comparing TGP with placebo, no treatment, or disease-modifying antirheumatic drugs for patients with RA will be retrieved. The primary outcomes will be disease improvement and disease remission. The secondary outcomes will be surrogate outcomes, symptoms, adverse effects, and quality of life. Two reviewers will independently extract data on participants, interventions, comparisons, outcomes, etc. The methodological quality of each included study will be evaluated using the Cochrane risk of bias tool, and the strength of evidence on prespecified outcomes will be assessed in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Review Manager 5.3 software will be used for data analyses. Meta-analyses will be performed if the data are sufficiently homogeneous, both statistically and clinically. Possible publication bias will also be checked using funnel plots once the number of included studies is sufficient. Ethics and dissemination Ethics approval is not required, as this study will not involve patients. The results of this study will be submitted to a peer-reviewed journal for publication, to inform both clinical

  17. Increased incidence of rheumatoid arthritis in multiple sclerosis

    PubMed Central

    Tseng, Chia-Chun; Chang, Shun-Jen; Tsai, Wen-Chan; Ou, Tsan-Teng; Wu, Cheng-Chin; Sung, Wan-Yu; Hsieh, Ming-Chia; Yen, Jeng-Hsien

    2016-01-01

    Abstract Past studies have shown inconsistent results on whether there is an association between multiple sclerosis (MS) and rheumatoid arthritis. To investigate the possible relationship between the 2 autoimmune diseases, we performed a nationwide cohort study utilizing the National Health Insurance Research Database and the Registry of Catastrophic Illness. A total of 1456 newly diagnosed patients with MS and 10,362 control patients were matched for age, sex, and initial diagnosis date. Patients with MS had a higher incidence of rheumatoid arthritis (age-adjusted standardized incidence ratio: 1.72; 95% confidence interval = 1.01–2.91). There was a positive correlation in being diagnosed with rheumatoid arthritis in patients previously diagnosed with MS when stratified by sex and age. The strength of this association remained statistically significant after adjusting for sex, age, and smoking history (hazard ratio: 1.78, 95% confidence interval = 1.24–2.56, P = 0.002). In conclusion, this study demonstrates that a diagnosis of MS increased the likelihood of a subsequent diagnosis of rheumatoid arthritis in patients, independent of sex, age, and smoking history. PMID:27368008

  18. A controlled study of concurrent therapy with a nonacetylated salicylate and naproxen in rheumatoid arthritis.

    PubMed

    Furst, D E; Blocka, K; Cassell, S; Harris, E R; Hirschberg, J M; Josephson, N; Lachenbruch, P A; Trimble, R B; Paulus, H E

    1987-02-01

    Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis (RA) have yielded conflicting results. We used standard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations. We used doses of choline magnesium trisalicylate, adjusted to achieve therapeutic serum salicylate concentrations, and naproxen in a randomized, double-blind, placebo-controlled cross-over study of full dose trisalicylate (CMT), full dose naproxen (N), full dose of both (CMT-N), and half dose of both (cmt-n) to examine their relative efficacy and toxicity in treating RA. CMT-N was statistically superior to all other treatments in only 1 of 12 efficacy variables, but was equal to N and better than CMT or cmt-n for 7 variables. There were minimal differences among treatments for the other 4 efficacy variables. The mean percentage difference for the efficacy variables between CMT-N and N was 3%, between CMT-N and CMT was 10.6%, and between CMT-N and cmt-n was 10.5%. Thirteen percent of patients manifested toxic reactions during the initial open dose-adjustment salicylate run-in phase. During the double-blind phases of the study, CMT-N was more toxic than N, CMT, or cmt-n (7.5% versus 3.4%, 1.8%, and 3.7%, respectively). Tinnitus was more common when full-dose CMT was used; N (N or CMT-N) was associated with increased skin toxicity. Gastrointestinal complaints were equally common with all regimens. CMT-N, although sometimes statistically superior to CMT, N, or cmt-n, showed no clinically important additive or synergistic effect versus N or CMT alone. PMID:3548732

  19. Myelitis and optic neuritis induced by a long course of etanercept in a patient with rheumatoid arthritis

    PubMed Central

    Yokoyama, Waka; Takada, Kazuki; Miyasaka, Nobuyuki; Kohsaka, Hitoshi

    2014-01-01

    A 64-year-old woman presented with an acute onset of myelitis and optic neuritis after 47 months of etanercept use for rheumatoid arthritis. Etanercept was discontinued and pulse methylprednisolone therapy (1000 mg/day for 3 days) was started, followed by a quick and complete resolution. Demyelination associated with antitumor necrosis factor agents, reported to develop mostly from 1 week to 12 months after the initiation of the agents, could develop after a few years and thus warrants vigilant monitoring. PMID:25085953

  20. Altered composition of gut microbiota in rheumatoid arthritis patients.

    PubMed

    Maeda, Yuichi; Kumanogoh, Atsushi; Takeda, Kiyoshi

    2016-01-01

      Manifestation of rheumatoid arthritis (RA) can be attributed to both genetic and environmental factors. Some researchers have been focusing on intestinal microbiota which is thought to be one of the environmental factors that may enhance the development of RA. The advancement of culture-independent, high throughput microbial DNA sequencing had enabled us to understand the interplay between intestinal microbiota and host immune systems. In this study, we have reviewed the previous findings in animal and human studies with respect to the role of intestinal microbiota in RA. Mouse models of arthritis have demonstrated that gut microbiota plays a critical role in the disease development. K/BxN and IL-1 receptor-antagonist knock-out mice did not develop disease in germ free condition, however, colonization of particular intestinal bacteria was sufficient to induce arthritis. Moreover, the dysbiosis was observed in the human RA patients from United States, China and Finland. Thus, we believe that endeavors to improve the dysbiosis would serve as a novel therapeutic or preventive strategy in RA patients. PMID:27181236

  1. Targeting GM-CSF in rheumatoid arthritis.

    PubMed

    Avci, Ali Berkant; Feist, Eugen; Burmester, Gerd-Rüdiger

    2016-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well-known as a haemopoietic growth factor. However, it is also essential in regulating functions of mature myeloid cells such as macrophages. Preclinical studies and observations of flares of arthritis in patients following GM-CSF treatment supported its important contribution to the pathogenesis of rheumatoid arthritis (RA). As the most advanced compound, mavrilimumab, a monoclonal antibody against GM-CSF receptor, has already completed phase II trials with a long term of follow-up period of 74 weeks. During this exposure period, an acceptable sustained safety and tolerability profile has been observed addressing the concerns of development of cytopenias or pulmonary alveolar proteinosis. Of note, a rapid and sustained efficacy and normalisation of acute phase reactants were consistently shown in studies both targeting GM-CSF and its receptor. Its tumour necrosis factor (TNF) independent mode of action with concurrent blockade of GM-CSF as well as IL-17 signalling reported from preclinical studies supports the assumption that it can be a useful biologic and an alternative agent in TNF inhibitor resistant patients with RA. Therefore, subsequent studies are warranted to investigate the safety and efficacy of GM-CSF blocking agents in different subgroups of RA. PMID:27586802

  2. Rheumatoid Arthritis and Periodontal Disease. An Update.

    PubMed

    Venkataraman, Archana; Almas, Khalid

    2015-01-01

    A review of the epidemiological, pathological and immunological relationships between two chronic inflammatory diseases: rheumatoid arthritis (RA) and periodontal disease (PD). RA is a chronic inflammatory disease of the joints, characterized by loss of connective tissue and mineralized structures, the so-called "synovial membrane." Periodontitis is the inflammatory destruction of the periodontal attachment and alveolar bone. While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are similar. And it is possible that individuals manifesting both PD and RA may suffer from a unifying underlying systemic deregulation of the inflammatory response. There is an overproduction of a variety of cytokines and MMPs that appears to be common in both diseases. Oral health parameters should be more closely monitored in patients with RA, an autoimmune disease. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Interventions to prevent, minimize or treat periodontitis in arthritis patients will definitely promise a better quality of life for these patients. PMID:26521325

  3. Inhibition of GSK-3β Alleviates Collagen II-Induced Rheumatoid Arthritis in Rats

    PubMed Central

    Zhou, Haiyan; Liu, Jun; Zeng, Jiashun; Hu, Bailong; Fang, Xiuyi; Li, Long

    2016-01-01

    Background 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. Material/Methods 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. Results 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. Conclusions 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. PMID:27029564

  4. [Immunodeficiency-associated Burkitt lymphoma developed in a patient receiving a long-term methotrexate therapy for rheumatoid arthritis].

    PubMed

    Katsuragi, Takefumi; Iwashige, Atsushi; Tsukada, Junichi

    2016-01-01

    An increased risk of lymphoproliferative disorders (LPD) has been demonstrated in patients treated with methotrexate (MTX) for rheumatoid arthritis (RA). The role of Epstein-Barr virus (EBV) has been discussed in the pathogenesis of immunodeficiency-associated LPDs. We herein present a RA patient, who developed Burkitt lymphoma during MTX treatment. The patient was a 61-year-old Japanese female with a 10-year history of weekly MTX therapy for RA. She presented with a one-month history of submandibular lymph node swelling and fever. Remarkable increases in serum lactate dehydrogenase and blood EBV DNA were observed. Serology for HIV was negative. Biopsy specimens demonstrated diffuse proliferation of medium-sized lymphoid cells. The cells were positive for CD10, CD20 and BCL6, and negative for BCL2, MUM1, terminal deoxynucleotidyl transferase and CD34. The MIB-1 index was almost 100%. EBV in the tumor cells was identified by using EBV-encoded RNA in situ hybridization. A chromosomal translocation t(8;14) was found and further confirmed by fluorescence in situ hybridization. Her condition improved following discontinuation of MTX and initiation of prednisolone. After three cycles of a dose-reduced CHOP-like regimen, chemotherapy was discontinued due to severe complications. However, there has been no sign of recurrence for six years to date without additional intensive chemotherapy. PMID:26861097

  5. Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis.

    PubMed

    Peres, Raphael Sanches; Liew, Foo Y; Talbot, Jhimmy; Carregaro, Vanessa; Oliveira, Rene D; Almeida, Sergio L; França, Rafael F O; Donate, Paula B; Pinto, Larissa G; Ferreira, Flavia I S; Costa, Diego L; Demarque, Daniel P; Gouvea, Dayana Rubio; Lopes, Norberto P; Queiroz, Regina Helena C; Silva, Joao Santana; Figueiredo, Florencio; Alves-Filho, Jose Carlos; Cunha, Thiago M; Ferreira, Sérgio H; Louzada-Junior, Paulo; Cunha, Fernando Q

    2015-02-24

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4(+)CD25(+)FoxP3(+)) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39(+)CD4(+)CD25(+)FoxP3(+) Tregs than the healthy controls. Tregs produce adenosine (ADO) through ATP degradation by sequential actions of two cell surface ectonucleotidases: CD39 and CD73. Tregs from UR-MTX expressed a lower density of CD39, produced less ADO, and had reduced suppressive activity than Tregs from R-MTX. In a prospective study, before MTX treatment, UR-MTX expressed a lower density of CD39 on Tregs than those of R-MTX or control (P < 0.01). In a murine model of arthritis, CD39 blockade reversed the antiarthritic effects of MTX treatment. Our results demonstrate that MTX unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production. Our findings thus provide hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Furthermore, our data suggest that low expression of CD39 on Tregs could be a noninvasive biomarker for identifying MTX-resistant RA patients. PMID:25675517

  6. Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis

    PubMed Central

    Peres, Raphael Sanches; Liew, Foo Y.; Talbot, Jhimmy; Carregaro, Vanessa; Oliveira, Rene D.; Almeida, Sergio L.; França, Rafael F. O.; Donate, Paula B.; Pinto, Larissa G.; Ferreira, Flavia I. S.; Costa, Diego L.; Demarque, Daniel P.; Gouvea, Dayana Rubio; Lopes, Norberto P.; Queiroz, Regina Helena C.; Silva, Joao Santana; Figueiredo, Florencio; Alves-Filho, Jose Carlos; Cunha, Thiago M.; Ferreira, Sérgio H.; Louzada-Junior, Paulo; Cunha, Fernando Q.

    2015-01-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39+CD4+CD25+FoxP3+ Tregs than the healthy controls. Tregs produce adenosine (ADO) through ATP degradation by sequential actions of two cell surface ectonucleotidases: CD39 and CD73. Tregs from UR-MTX expressed a lower density of CD39, produced less ADO, and had reduced suppressive activity than Tregs from R-MTX. In a prospective study, before MTX treatment, UR-MTX expressed a lower density of CD39 on Tregs than those of R-MTX or control (P < 0.01). In a murine model of arthritis, CD39 blockade reversed the antiarthritic effects of MTX treatment. Our results demonstrate that MTX unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production. Our findings thus provide hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Furthermore, our data suggest that low expression of CD39 on Tregs could be a noninvasive biomarker for identifying MTX-resistant RA patients. PMID:25675517

  7. 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.

  8. Diffuse alveolar damage in a patient with rheumatoid arthritis under prolonged leflunomide treatment: A Case Report and Literature Review.

    PubMed

    Keng, Li-Ta; Lin, Mong-Wei; Huang, Hsien-Neng; Chung, Kuei-Pin

    2016-06-01

    Patients with rheumatoid arthritis (RA) often have pulmonary involvement, and interstitial lung disease (ILD) is the primary manifestation, in which diffuse alveolar damage (DAD) is a rare histopathologic pattern. Leflunomide (LEF) is a frequently prescribed disease-modifying antirheumatic drug for treating RA. LEF-related ILD in the form of DAD has been reported in patients with RA, with the duration of LEF treatment before symptom onset ranging from 6 to 1204 days.We present a case of elderly woman with RA under prolonged LEF treatment for >9 years (3291 days), who had acute respiratory failure with the initial presentation of exertional dyspnea, fever, chills, and productive cough for 2 days. The histopathologic result of surgical lung biopsy was compatible with DAD. She was diagnosed as having LEF-related ILD, based on correlated clinical history, compatible histopathologic examination and excluding possible infection after extensive survey.Although the causative role of LEF cannot be confirmed, this case still hints that LEF-related DAD may occur even if LEF has been prescribed for a prolonged period. PMID:27368035

  9. The autotaxin-lysophosphatidic acid pathway in pathogenesis of rheumatoid arthritis.

    PubMed

    Orosa, Beatriz; García, Samuel; Conde, Carmen

    2015-10-15

    Lysophosphatidic acid (LPA) is a phospholipid that is mainly produced by the hydrolysis of lysophosphatidylcholine (LPC) by lysophospholipase D, which is also called autotaxin (ATX). LPA interacts with specific G-protein coupled receptors and is involved in the regulation of cellular survival, proliferation, differentiation and motility. LPA also has roles in several pathological disorders, such as cancer and pulmonary, dermal and renal fibrosis. The involvement of the ATX-LPA pathway has recently been demonstrated in inflammatory responses and apoptosis of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis and during the development of experimental arthritis. This review summarises the current literature of the ATX-LPA pathway in rheumatoid arthritis. PMID:26297977

  10. Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study

    PubMed Central

    Rho, Young Hee; Man, Ada; Zhu, Yanyan; Zhang, Yuqing; Love, Thorvardur Jon; Ogdie, Alexis; Gelfand, Joel M.; Choi, Hyon K.

    2014-01-01

    Objective. The objective of this study was to evaluate the incidence of diabetes among patients with PsA and RA in the general population. Methods. We conducted a cohort study using an electronic medical records database representative of the UK general population (1986–2010). We estimated hazard ratios (HRs) for incident diabetes in PsA, psoriasis and RA cohorts compared with age- and sex-matched comparison cohorts without the corresponding conditions, adjusting for BMI, smoking, alcohol use, co-morbidities and glucocorticoids at baseline. Results. Cohorts included 4196 persons with PsA, 59 281 with psoriasis and 11 158 with RA, with mean follow-up times of 5.9, 5.8 and 5.5 years, respectively. Incidence rates for diabetes were 7.3, 6.4 and 6.3 cases per 1000 person-years among individuals with PsA, psoriasis and RA, respectively. Age- and sex-matched HRs for diabetes were 1.72 (95% CI 1.46, 2.02) in PsA, 1.39 (95% CI 1.32, 1.45) in psoriasis and 1.12 (95% CI 1.01, 1.25) in RA. After adjustment for BMI, smoking and alcohol, the HRs were attenuated substantially (1.43, 1.24 and 1.00, respectively). With further adjustment for baseline glucocorticoid use and co-morbidities, the HRs were 1.33 (1.09, 1.61) in PsA, 1.21 (1.15, 1.27) in psoriasis and 0.94 (0.84, 1.06) in RA. Conclusion. This general population study suggests an increased incidence of diabetes in PsA and RA, which is substantially explained by obesity and lifestyle factors. These findings support the importance of managing such factors in PsA and RA patients. PMID:24185762

  11. Silent myocardial infarction secondary to cardiac autonomic neuropathy in a patient with rheumatoid arthritis.

    PubMed

    Unnikrishnan, Dileep; Jacob, Aasems; Anthony Diaz, Mark; Lederman, Jeffrey

    2016-01-01

    An 83-year-old female patient with rheumatoid arthritis and hypertension presented to the emergency department with fever and chills of 1 day duration. On examination, temperature was 100.9 F, heart rate 111/min and she had orthostatic hypotension. Laboratory tests showed elevated blood urea nitrogen and white cell count. The patient underwent treatment for symptomatic urinary tract infection and while her fever and leucocytosis resolved, tachycardia persisted. An EKG done showed T inversions in leads II, III, arteriovenous fistula, V2 and V3. Troponin-I was elevated. Nuclear stress test revealed apical wall motion abnormality confirming myocardial infarction. Ewing's tests were carried out at bedside and these diagnosed severe autonomic neuropathy. Rheumatoid arthritis can cause cardiac autonomic neuropathy from chronic inflammation. This case entails the importance of assessing and detecting cardiac autonomic neuropathy in chronic inflammatory conditions, and the need to be cautious of acute coronary events in these patients, even for minimal or no symptoms. PMID:27489064

  12. Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases.

    PubMed Central

    Spector, T D; Woodward, L; Hall, G M; Hammond, A; Williams, A; Butler, M G; James, I T; Hart, D J; Thompson, P W; Scott, D L

    1992-01-01

    Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss. PMID:1444626

  13. Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a murine model of rheumatoid arthritis.

    PubMed

    Matsuo, Yusuke; Mizoguchi, Fumitaka; Saito, Tetsuya; Kawahata, Kimito; Ueha, Satoshi; Matsushima, Kouji; Inagaki, Yutaka; Miyasaka, Nobuyuki; Kohsaka, Hitoshi

    2016-02-12

    Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP and wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G2/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA. PMID:26806309

  14. Influence of human leucocyte antigen‐DRB1 on the susceptibility to rheumatoid arthritis and on the production of anti‐cyclic citrullinated peptide antibodies in a Portuguese population

    PubMed Central

    Ligeiro, D; Fonseca, J E; Abade, O; Abreu, I; Cruz, M; Nero, P; Cavaleiro, J; Teles, J; Trindade, H; Caetano, J M; Branco, J

    2007-01-01

    Objective To clarify the influence of the HLA‐DRB1 locus on the susceptibility to rheumatoid arthritis and the production of anti‐cyclic citrullinated peptide antibodies (anti‐CCP) in a Portuguese population. Methods: 141 patients with rheumatoid arthritis fulfilling the American College of Rheumatology 1987 revised criteria for rheumatoid arthritis were compared with 150 healthy controls. Human leucocyte antigen (HLA)‐DRB1 locus genotyping was assessed by polymerase chain reaction reverse probing assays and sequence‐specific primers. Anti‐CCP antibodies were quantified by ELISA in patients with rheumatoid arthritis. Frequencies between groups were compared by the two‐sided Fisher's exact test and considered significant if p<0.05. Results The HLA‐DRB1*04 and HLA‐DRB1*10 groups were highly associated with rheumatoid arthritis (p<0.001 and p = 0.031, respectively). High titres of anti‐CCP antibodies were largely associated with the presence of HLA‐DRB1*04/10. Conclusion The well‐recognised susceptibility alleles to rheumatoid arthritis, HLA‐DRB1*04, were associated with rheumatoid arthritis in Portuguese patients. The relatively rare DRB1*10 was also associated with rheumatoid arthritis, as was described previously in other southern European countries. Both groups were associated with high anti‐CCP titres, reinforcing its relevance to disease onset. PMID:16793843

  15. Pulmonary function in rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.

    PubMed

    Beyeler, C; Jordi, B; Gerber, N J; Im Hof, V

    1996-05-01

    Lung volumes and gas exchange were investigated prospectively in 96 patients with rheumatoid arthritis selected without regard to pulmonary disorders and treated with i.m. methotrexate (MTX) injections [mean weekly dose 13.0 mg (5th-95th percentile (5-95 PC) 7.6-20.8)]. Individual changes over time during MTX treatment [mean duration 2.9 yr (5-95 PC 0.4-5.3)] were assessed by regression analyses in each individual. Forced vital capacity (FVC) remained stable in the majority of patients [mean annual change +0.8% (5-95 PC -8.1 to +14.0) of calculated normal value]. In addition, transfer factor using the indicator gas CO (TL,CO) was unaltered in most patients [mean annual change -2.1% (5-95 PC -16.2 to +11.8) of predicted value]. However, there were significant decreases in the forced expiratory volume in 1 s (FEV1) before and after inhalation of 0.2 mg salbutamol [mean annual change -0.8% (5-95 PC -8.4 to +3.2) and -1.3% (5-95 PC -7.8 to +3.9) of the FVC measured, respectively]. In addition, there were significant increases in alveolar-arterial Po2 gradients (P(A-a),O2) at rest and after exercise [mean annual change +1.7 mmHg (5-95 PC -5.2 to +12.2) and +1.8 mmHg (5-95 PC -3.5 to 9.0), respectively]. Nevertheless, the amounts were small in view of the reliability of the methods applied and reflect, at least in part, the normal process of ageing. The annual change in FEV1/FVC was negatively correlated with FEV1/FVC at baseline (Rs = -0.46, P < 0.001). The annual change in TL,CO was also negatively correlated with TL,CO at baseline (Rs = -0.31, P = 0.028). No other risk factors for deterioration of lung volumes or gas exchange were found, including mean weekly MTX dose, age, gender, smoking, presence of rheumatoid factor and pulmonary function at baseline. We conclude that MTX has no major effect on pulmonary function in the majority of patients and that there is no evidence that patients with pre-existing pulmonary disease are at increased risk for further

  16. Could Early Rheumatoid Arthritis Resolve After Periodontitis Treatment Only?

    PubMed Central

    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

    2014-01-01

    Abstract 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. PMID:25501069

  17. 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. PMID:27281595

  18. Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later: a population-based study.

    PubMed

    Wallin, Karin; Solomon, Alina; Kåreholt, Ingemar; Tuomilehto, Jaakko; Soininen, Hilkka; Kivipelto, Miia

    2012-01-01

    Inflammation has been associated with Alzheimer's disease (AD) and dementia. The association between rheumatoid arthritis (RA) or arthritis and dementia/AD has been investigated in several case-control or hospital- and register-based studies with mixed results. This long-term population-based study investigates the association between presence of joint disorders (RA and other joint disorders) in midlife and cognitive status later in life. 1,449 participants were first evaluated in 1972, 1977, 1982, and 1987 and follow-up was performed after 21 years. A self-administered questionnaire including questions on joint disorders was used at both evaluations. Cognitive status (control, mild cognitive impairment, dementia/AD) was assessed at follow-up. The presence of any joint disorder in midlife was significantly associated with a worse cognitive status later in life: OR (95% CI) in an ordinal logistic regression analysis adjusted for age, gender, follow-up time, education, APOEε4, body mass index, smoking, drug treatment, and diabetes was 1.96 (1.17-3.28). For RA only, OR (95% CI) was 2.77 (1.26-6.10). The correlation remained significant for RA when AD was considered instead of dementia OR (95% CI) 2.49 (1.09-5.67). The presence of joint disorders, especially RA, at midlife seems to be associated with a worse cognitive status later in life. Given the chronic inflammatory component of RA, this study suggests that inflammatory mechanisms may have an important role in increasing the risk of cognitive impairment and dementia/AD. PMID:22647255

  19. Angiotensin II in inflammation, immunity and rheumatoid arthritis

    PubMed Central

    Chang, Y; Wei, W

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that is characterized by increased cardiovascular morbidity and mortality, independent of the traditional risk factors for cardiovascular disease. Although classically known for its role in the regulation of circulatory homeostasis, angiotensin II (Ang II) is recognized to act as a powerful proinflammatory mediator. Some research has showed that Ang II plays important roles in autoimmune diseases, including RA, systemic lupus erythematosus and multiple sclerosis. Ang II blockers prove effective in reducing inflammation and autoimmunity in rheumatic diseases and their relative safety, together with their effects for reducing the cardiovascular disease risk, suggest that Ang II blockers may at least act as effective adjunctive therapy for disease control in patients with RA. The present review focuses systematically on the potential impact of Ang II and its receptors on inflammation and immunomodulation in patients with RA. PMID:25302847

  20. Staphylococcal Enterotoxin A Detection from Rheumatoid Arthritis Patients’ Blood and Synovial Fluid

    PubMed Central

    Ataee, Ramezan Ali; Kahani, Mahboobeh Sadat; Alishiri, Gholam Hossein; Ahamadi, Zyenab

    2016-01-01

    Introduction Direct detection of microbial super antigens in synovial fluid of patients with rheumatoid arthritis may be able to guide to the design of cost-effective therapies. The purpose of this study was to assess the existence of Staphylococcal enterotoxin A (superantigen A) in the synovial fluid of patients with RA by the PCR and ELISA methods. Methods This experimental study was conducted on the synovial fluid of 103 RA patients from Baqiyatallah University of Medical Sciences’ Rheumatology Clinic in Tehran, Iran in 2011–2014. Bacterial cultures, polymerase chain reaction with specific primer pairs and enzyme-linked immunosorbent assay (ELISA) methods were used. The PCR products were subjected to sequence as a confirmatory molecular method results. The data were descriptively analyzed by SPSS Version 19. Results The bacteriological study result indicated that, in four cases (3.8%) of the patients, bacterial strains were isolated. The result of PCR molecular method for staphylococcal enterotoxin A gene showed that, 42 of the patients (40.7%) tested positive for the ent A gene. The results of ELISA were positive for staphylococcal enterotoxin A (superantigen A) in 51 cases (49.51%) of the patients’ synovial fluids. The results indicated that the possibility of detecting superantigen A in the SF of RA patients, but the origin of the enterotoxin A gene remained unknown. Conclusions The findings of this study may be able to alter the actual theory on the pathogenesis, diagnosis, and treatment of RA patients. In addition, the results have shown the probability of an endogenous origin for the involved superantigen A in RA patients’ synovial fluids. PMID:27053990

  1. A Decision Tool to Improve the Quality of Care in Rheumatoid Arthritis

    PubMed Central

    Fraenkel, Liana; Peters, Ellen; Charpentier, Peter; Olsen, Blair; Errante, Lanette; Schoen, Robert T.; Reyna, Valerie

    2012-01-01

    Objectives Despite the importance of achieving tight control, many rheumatoid arthritis (RA) patients are not effectively treated with disease modifying anti-rheumatic drugs (DMARDs). The objective of this study was to develop a decision support tool to inform RA patients with ongoing active disease about the risks and benefits related to biologic therapy. Methods We developed a balanced, web-based, decision support tool. Options, values and probabilistic information were described using theoretically supported formulations. We conducted a pre-post test study to assess preliminary evidence of the tool’s efficacy in improving knowledge related to biologics, clarity of values, willingness to take a biologic and informed choice. Results We interviewed 104 subjects; mean age = 62; 84% female, 86% White; median duration of RA =13 years. Knowledge (coded on a 0 to 20 scale) and willingness to take a biologic (coded on a 0 to 10 scale) significantly increased after viewing the tool (mean differences = 3.1 and 1.4 respectively, both p < 0.0001). Perceived knowledge and value clarity (coded on 0 to 100 scales) also significantly improved (mean differences 20.4 and 20.7 respectively, both p<0.001). The proportion of subjects making an informed, value-concordant choice increased substantially from 35% to 64%. Conclusion A tool designed to effectively communicate the risks and benefits associated with biologic therapy increased knowledge, patient willingness to escalate care, and the likelihood of making an informed choice. The results of this study support the need for a clinical trial to examine the impact of the tool in clinical practice. PMID:22392766

  2. Effect of intensive exercise on patients with active rheumatoid arthritis: a randomised clinical trial

    PubMed Central

    van den Ende, C H M; Breedveld, F; le Cessie, S; Dijkmans, B; de Mug, A W; Hazes, J

    2000-01-01

    OBJECTIVE—To investigate the effects of a dynamic, intensive exercise regimen on pain, disease activity, and physical functioning in active rheumatoid arthritis (RA).
METHODS—64 patients with RA with a mean age of 60 (13) years and mean disease duration of 8 (8) years, admitted to hospital because of active disease, were randomly assigned to an intensive exercise programme or to a conservative exercise programme during their period in hospital with a mean length of 30 (14) days. The intensive exercise programme consisted of knee and shoulder dynamic and isometric muscle strengthening exercises against resistance five times a week and conditioning bicycle training three times a week and was supplemental to the conservative exercise programme of range of motion and isometric exercises. Indices of disease activity, pain, muscle strength, and functional ability were assessed at 0, 3, 6, 12, and 24 weeks by a blinded observer.
RESULTS—The medical treatment during the study was the same in both groups. Both groups improved in measures of disease activity, differences between groups were not statistically significant. The mean improvement in disease activity score at 24 weeks in the intensive and conservative exercise group was −1.4 (1.5) and −0.7 (1.4), respectively. Measures of physical functioning improved significantly for patients in the intensive exercise group, and differences between groups were statistically significant for measures of muscle strength.
CONCLUSION—A short term intensive exercise programme in active RA is more effective in improving muscle strength than a conservative exercise programme and does not have deleterious effects on disease activity.

 PMID:10913058

  3. Construct Validation of a Multidimensional Computerized Adaptive Test for Fatigue in Rheumatoid Arthritis

    PubMed Central

    Nikolaus, Stephanie; Bode, Christina; Taal, Erik; Vonkeman, Harald E.; Glas, Cees A. W.; van de Laar, Mart A. F. J.

    2015-01-01

    Objective Multidimensional computerized adaptive testing enables precise measurements of patient-reported outcomes at an individual level across different dimensions. This study examined the construct validity of a multidimensional computerized adaptive test (CAT) for fatigue in rheumatoid arthritis (RA). Methods The ‘CAT Fatigue RA’ was constructed based on a previously calibrated item bank. It contains 196 items and three dimensions: ‘severity’, ‘impact’ and ‘variability’ of fatigue. The CAT was administered to 166 patients with RA. They also completed a traditional, multidimensional fatigue questionnaire (BRAF-MDQ) and the SF-36 in order to examine the CAT’s construct validity. A priori criterion for construct validity was that 75% of the correlations between the CAT dimensions and the subscales of the other questionnaires were as expected. Furthermore, comprehensive use of the item bank, measurement precision and score distribution were investigated. Results The a priori criterion for construct validity was supported for two of the three CAT dimensions (severity and impact but not for variability). For severity and impact, 87% of the correlations with the subscales of the well-established questionnaires were as expected but for variability, 53% of the hypothesised relations were found. Eighty-nine percent of the items were selected between one and 137 times for CAT administrations. Measurement precision was excellent for the severity and impact dimensions, with more than 90% of the CAT administrations reaching a standard error below 0.32. The variability dimension showed good measurement precision with 90% of the CAT administrations reaching a standard error below 0.44. No floor- or ceiling-effects were found for the three dimensions. Conclusion The CAT Fatigue RA showed good construct validity and excellent measurement precision on the dimensions severity and impact. The dimension variability had less ideal measurement characteristics

  4. Presence of Cyclophilin A in Synovial Fluids of Patients with Rheumatoid Arthritis

    PubMed Central

    Billich, Andreas; Winkler, Gottfried; Aschauer, Heinrich; Rot, Antal; Peichl, Peter

    1997-01-01

    Cyclophilins have been suggested to act as leukocyte chemotactic factors produced in the course of inflammation. Therefore we looked for the presence of cyclophilins in the synovial fluids (SF) from patients with rheumatoid arthritis (RA). Peptidyl prolyl cis–trans isomerase activity (PPIase) was measured in SF from knee punctures of 26 patients with RA and five patients with knee osteoarthritis (OA). PPIase was detected in SF from RA patients, but not in samples from OA patients. Enzyme activity was sensitive to inhibition by cyclosporin A (IC50 = 28–50 nM). Estimated concentrations of the SF-derived cyclophilin based on the enzyme activity were in the range of 11 to 705 nM. The presence of cyclophilin in the SF showed disease correlation; its concentration correlated with the number of cells in the SF (r   = 0.91, P <0.0001) and with the percentage of neutrophils in the cellular infiltrate and was higher in more acute cases of joint swelling. In immunoblots of partially purified preparations of SF from RA patients, an ∼18-kD protein band reacted with polyclonal antibodies that recognize cyclophilin A and B, but not with antibodies specific for cyclophilin B. Sequencing of this protein revealed identity of the NH2-terminal amino acids with those of human cyclophilin A. The finding is unexpected since cyclophilin B rather than A is generally regarded as the secreted isoform, the presence of cyclophilin A being confined to the cytoplasm. Our data support the hypothesis that cyclophilins may contribute to the pathogenesis of inflammatory diseases, possibly by acting as cytokines. This may offer a possible explanation of the effectiveness of cyclosporin A in RA, in addition to the known immunosuppressive effects of the drug. PMID:9120404

  5. The pendulum test as a tool to evaluate passive knee stiffness and viscosity of patients with rheumatoid arthritis

    PubMed Central

    Valle, Maria S; Casabona, Antonino; Sgarlata, Rosaria; Garozzo, Rosaria; Vinci, Maria; Cioni, Matteo

    2006-01-01

    Background The pendulum test of Wartenberg is a technique commonly used to measure passive knee motion with the aim to assess spasticity. We used this test to evaluate changes of the knee angular displacement, passive stiffness and viscosity in rheumatoid arthritis patients. Stiffness and viscosity represent passive resistances to joint motion associated with the structural properties of the joint tissue and of the muscular-tendon complex. Stiffness can be considered an intrinsic property of the tissues to resist deformation, while viscosity is related to cohesive forces between adjacent layers of tissues. Both parameters may influence the joint range of motion affecting angular displacement. Methods Nine women with rheumatoid arthritis were compared with a group of healthy women. With the subject half-lying, the relaxed knee was dropped from near-full extension and the characteristics of the ensuring damped unsustained knee oscillation evaluated. The kinematics of leg oscillations was recorded using ultrasonic markers (Zebris CMS HS 10) and the kinetic data were calculated from kinematic and anthropometric measures. Results Knee stiffness significantly increased (p < 0.001) in patients with respect to the control group, while differences in viscosity were not significant. Moreover, the amplitudes of first knee flexion (the maximal flexion excursion after knee release) and first knee extension (the maximal extension excursion after the first knee flexion) were significantly decreased (p < 0.001). A regression analysis showed that disease severity correlated moderately with stiffness (R2 = 0.68) and first flexion (R2 = 0.78). Using a multivariate regression, we found that increasing stiffness was the main factor for the reduction of flexion and extension motions. Conclusion We showed that the Wartenberg test can be considered a practical tool to measure mechanical changes of knee caused by rheumatoid arthritis. This novel application of Wartenberg test could be

  6. A prospective study of renal disease in patients with early rheumatoid arthritis

    PubMed Central

    Koseki, Y; Terai, C; Moriguchi, M; Uesato, M; Kamatani, N

    2001-01-01

    OBJECTIVES—This prospective study was designed to clarify the frequency, causes, and clinical course of renal disease in patients with early rheumatoid arthritis (RA).
METHODS—235 patients (185 women, mean age 49.4 years) with early RA of less than one year's duration were enrolled and assessed monthly. Proteinuria was defined as a positive dipstick result and microscopic haematuria was defined as the presence of ⩾5 red blood cells per high power field. Urinary abnormalities lasting three months or longer were defined as persistent abnormalities.
RESULTS—At entry, 40 patients exhibited haematuria, two had a raised serum creatinine concentration, and none had proteinuria. During the observation period (average 42 months), persistent haematuria was found in 43, persistent proteinuria in 17, and a raised serum creatinine concentration in 14 patients. Persistent proteinuria was caused by drugs in 14 of 17 patients and disappeared in most cases. Risk factors for drug induced proteinuria included a raised C reactive protein and erythrocyte sedimentation rate and age over 50 at entry. Drugs resulted in a raised serum creatinine concentration in eight of 14 patients. The incidence of haematuria at entry did not differ among patients who had been treated with non-steroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, or no drugs. In some patients with isolated haematuria, the haematuria appeared when the activity of RA was high and resolved when it was low.
CONCLUSIONS—This study suggests that a raised serum creatinine concentration or persistent proteinuria in patients with early RA is predominantly drug related whereas, in contrast, isolated haematuria is more directly associated with the activity of the disease process.

 PMID:11247860

  7. [Phaeomycotic cyst caused by Exophiala xenobiotica in a patient with rheumatoid arthritis and lung cancer].

    PubMed

    Urano, Shoko; Suzuki, Yoko; Anzawa, Kazushi; Ohishi, Tsuyoshi; Kuroishi, Shigeki; Itoh, Naomi; Okada, Takathika; Mochizuki, Takashi

    2014-01-01

    In black fungal infections, Exophiala species are frequently encountered as causative agents of human mycosis, particularly in immunocompromised patients. Among them, Exophiala jenselmei was previously reported as the most common etiological agent. Advances in molecular taxonomy proved this taxon to be heterogeneous, and led to newly introduced or redefined species. Exophiala xenobiotica is one of the novel species differentiated from E. jenselmei on the basis of molecular phylogeny.Here, we report a case of pheomycotic cyst caused by E. xenobiotica, which was well controlled via drainage and local thermotherapy. A 70-year-old man developed a cystic nodular lesion on the dorsum of his right thumb over the previous 3 months. He had been treated with prednisolone and methotrexate for 4 years for rheumatoid arthritis. The patient also had lung cancer with vertebral bone metastasis. Direct microscopic examination of the greenish pus aspirated from the cyst revealed mycelial elements. Culture of the pus on blood and Sabouraud dextrose agar yielded numerous black colonies multiple times. Histopathological examination of a biopsy specimen showed subcutaneous abscess formation surrounded by granulomatous tissues. Faintly pigmented pseudohyphae were seen within the abscess. The presence of melanin in the fungal cells was determined by Fontana-Masson staining. Initial microscopic examination of the isolate revealed annellidic conidiogenous cells, suggestive of E. jenselmei. This strain was further identified as E. xenobiotica by sequence analysis of the internal transcribed spacer (ITS) region of ribosomal RNA, showing a 100% sequence homology with the strain type.Pheomycotic cysts should be considered on identifying a slowly developing chronic subcutaneous abscess in immunocompromised patients. Sequencing is recommended for accurate species identification of causative pathogens. PMID:25742995

  8. Inflammation as a Risk of Developing Chronic Kidney Disease in Rheumatoid Arthritis

    PubMed Central

    Kochi, Masako; Kohagura, Kentaro; Shiohira, Yoshiki; Iseki, Kunitoshi; Ohya, Yusuke

    2016-01-01

    Objective The relationship between chronic inflammation and the incidence of chronic kidney disease (CKD) remained not-clear in patients with rheumatoid arthritis (RA). This study aims to examine the relationship between persistently high C-reactive protein (CRP), a marker of inflammation, and the incidence of CKD in RA. Methods We retrospectively examined the relationship between the levels of CRP and incidence of CKD in 345 RA patients. The outcome of interest was incidence of CKD, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or positive dipstick testing for proteinuria for ≥3 months. We defined high CRP, as >3.0 mg/L. On the basis of three measurements of CRP for 6-months period, patients were divided into three groups: group 1, including patients with no high CRP values; group 2, patients with transient high CRP values (once or twice) and group 3, patients with persistently high CRP values. Results During a median follow-up period of 89 months, 14% of all patients developed CKD. The cumulative incidence of CKD was 7% in group 1, 14% in group 2 and 22% in group 3 (P = 0.008, log-rank test). In a multivariate analysis, including classical risk factors for CKD, persistently high CRP was an independent predictor of the incidence of CKD (hazard ratio, 3.00; 95% confidence interval, 1.23–8.53; P = 0.01). Conclusions Persistently high CRP was a significant risk factor for the incidence of CKD. Results suggest that persistent inflammation is a marker for the high risk of CKD in RA. PMID:27537204

  9. Estimating the burden of rheumatoid arthritis in Africa: A systematic analysis

    PubMed Central

    Dowman, Ben; Campbell, Ruth M.; Zgaga, Lina; Adeloye, Davies; Chan, Kit Yee

    2012-01-01

    Background Rheumatoid arthritis (RA) has an estimated worldwide prevalence of 1%. It is one of the leading causes of chronic morbidity in the developed world, but little is known about the disease burden in Africa. RA is often seen as a minor health problem and has been neglected in research and resource allocation throughout Africa despite potentially fatal systemic manifestations. This review aims to identify all relevant epidemiological literature pertaining to the occurrence of RA in Africa and calculate the prevalence and burden of disease. Methods A systematic literature review of Medline, Embase and Global Health Library retrieved a total of 335 publications, of which 10 population studies and 11 hospital studies met pre–defined minimum criteria for relevance and quality. Data on prevalence was extracted, analysed and compared between population and hospital studies. Differences between genders were also analysed. Findings The estimated crude prevalence of RA in Africa based on the available studies was 0.36% in 1990, which translates to a burden of 2.3 million affected individuals in 1990. Projections for the African population in 2010 based on the same prevalence rates would suggest a crude prevalence of 0.42% and the burden increased to 4.3 million. Only 2 population studies have been conducted after 1990, so projections for 2010 are uncertain. Hospital–based studies under–report the prevalence by about 6 times in comparison to population–based studies. Conclusion The availability of epidemiological information on RA in Africa is very limited. More studies need to be conducted to estimate the true burden and patterns of RA before appropriate health policies can be developed. PMID:23289081

  10. Process Evaluation of a Workplace Integrated Care Intervention for Workers with Rheumatoid Arthritis.

    PubMed

    van Vilsteren, M; Boot, C R L; Voskuyl, A E; Steenbeek, R; van Schaardenburg, D; Anema, J R

    2016-09-01

    Purpose To perform a process evaluation of the implementation of a workplace integrated care intervention for workers with rheumatoid arthritis to maintain and improve work productivity. The intervention consisted of integrated care and a participatory workplace intervention with the aim to make adaptations at the workplace. Methods The implementation of the workplace integrated care intervention was evaluated with the framework of Linnan and Steckler. We used the concepts recruitment, reach, dose delivered, dose received, fidelity and satisfaction with the intervention. Data collection occurred through patient questionnaires and medical records. Results Participants were recruited by sending a letter including a reply card from their own rheumatologist. In total, we invited 1973 patients to participate. We received 1184 reply cards, and of these, 150 patients eventually participated in the study. Integrated care was delivered according to protocol for 46.7 %, while the participatory workplace intervention was delivered for 80.6 %. Dose received was nearly 70 %, which means that participants implemented 70 % of the workplace adaptations proposed during the participatory workplace intervention. The fidelity score for both integrated care and the participatory workplace intervention was sufficient, although communication between members of the multidisciplinary team was limited. Participants were generally satisfied with the intervention. Conclusions This process evaluation shows that our intervention was not entirely implemented as intended. The integrated care was not delivered to enough participants, but for the intervention components that were delivered, the fidelity was good. Communication between members of the multidisciplinary team was limited. However, the participatory workplace intervention was implemented successfully, and participants indicated that they were satisfied with the intervention. PMID:26811171

  11. Temperature-responsive polymeric nanospheres containing methotrexate and gold nanoparticles: A multi-drug system for theranostic in rheumatoid arthritis.

    PubMed

    Costa Lima, Sofia A; Reis, Salette

    2015-09-01

    Inflammation plays a crucial role in rheumatoid arthritis progress. In the present work, a novel stealth polymeric nanospheres platform able to carry anti-inflammatory drugs and an imaging agent was developed. Incorporation of gold nanoparticles will allow photoacoustic imaging and near infra-red photothermal application. Through emulsion-diffusion evaporation technique methotrexate and gold nanoparticles were incorporated in the pegylated-poly(DL-lactic-co-glycolic acid) nanospheres. In vitro drug release assays revealed pH and temperature-dependence on gold nanoparticles. Blank nanospheres exhibited negligible in vitro cytotoxicity, while methotrexate-loaded nanospheres hampered monocytes and macrophages viability at a higher level than free methotrexate. Confocal fluorescent microscopy and flow cytometry revealed effective nanospheres internalization, and that their cellular uptake was energy dependent mediated by caveolae and clathrin-endocytosis mechanism. Finally, MTX-loaded multifunctional nanospheres containing gold lead to a significant reduction of IL-1β, IL-6 and TNF-α inflammatory cytokines produced by monocytes and macrophages upon in vitro inflammatory stimulation, suggesting a favorable anti-inflammatory activity. These results confirm that the multifunctional nanospheres represent a promising theranostic platform for RA diagnosis and intracellular treatment, by combining methotrexate and gold nanoparticles for a highly effective targeted chemo-photothermal therapy. PMID:25979151

  12. High Sodium Intake Is Associated With Self-Reported Rheumatoid Arthritis: A Cross Sectional and Case Control Analysis Within the SUN Cohort.

    PubMed

    Salgado, Eva; Bes-Rastrollo, Maira; de Irala, Jokin; Carmona, Loreto; Gómez-Reino, Juan J

    2015-09-01

    Sodium intake is a potential environmental factor for immune-mediated inflammatory diseases. The aim of this study is to investigate the association of sodium intake with rheumatoid arthritis. We performed a cross-sectional study nested in a highly educated cohort investigating dietary habits as determinants of disease. Daily sodium intake in grams per day was estimated from a validated food frequency questionnaire. We identified prevalent self-reported cases of rheumatoid arthritis. Logistic regression models were used to estimate the odds ratio for rheumatoid arthritis by sodium intake adjusting for confounders. Linear trend tests and interactions between variables were explored. Sensitivity analyses included age- and sex-matched case-control study, logistic multivariate model adjusted by residuals, and analysis excluding individuals with prevalent diabetes or cardiovascular disease. The effective sample size was 18,555 individuals (mean age 38-years old, 60% women) including 392 self-reported rheumatoid arthritis. Median daily sodium intake (estimated from foods plus added salt) was 3.47 (P25-75: 2.63-4.55) grams. Total sodium intake in the fourth quartile showed a significant association with rheumatoid arthritis (fully adjusted odds ratio 1.5; 95% CI 1.1-2.1, P for trend = 0.02). Never smokers with high sodium intake had higher association than ever smokers with high sodium intake (P for interaction = 0.007). Dose-dependent association was replicated in the case-control study. High sodium intake may be associated with a diagnosis of rheumatoid arthritis. This confirms previous clinical and experimental research. PMID:26376372

  13. High Sodium Intake Is Associated With Self-Reported Rheumatoid Arthritis: A Cross Sectional and Case Control Analysis Within the SUN Cohort

    PubMed Central

    Salgado, Eva; Bes-Rastrollo, Maira; de Irala, Jokin; Carmona, Loreto; Gómez-Reino, Juan J.

    2015-01-01

    Abstract Sodium intake is a potential environmental factor for immune-mediated inflammatory diseases. The aim of this study is to investigate the association of sodium intake with rheumatoid arthritis. We performed a cross-sectional study nested in a highly educated cohort investigating dietary habits as determinants of disease. Daily sodium intake in grams per day was estimated from a validated food frequency questionnaire. We identified prevalent self-reported cases of rheumatoid arthritis. Logistic regression models were used to estimate the odds ratio for rheumatoid arthritis by sodium intake adjusting for confounders. Linear trend tests and interactions between variables were explored. Sensitivity analyses included age- and sex-matched case–control study, logistic multivariate model adjusted by residuals, and analysis excluding individuals with prevalent diabetes or cardiovascular disease. The effective sample size was 18,555 individuals (mean age 38-years old, 60% women) including 392 self-reported rheumatoid arthritis. Median daily sodium intake (estimated from foods plus added salt) was 3.47 (P25–75: 2.63–4.55) grams. Total sodium intake in the fourth quartile showed a significant association with rheumatoid arthritis (fully adjusted odds ratio 1.5; 95% CI 1.1–2.1, P for trend = 0.02). Never smokers with high sodium intake had higher association than ever smokers with high sodium intake (P for interaction = 0.007). Dose-dependent association was replicated in the case–control study. High sodium intake may be associated with a diagnosis of rheumatoid arthritis. This confirms previous clinical and experimental research. PMID:26376372

  14. Current medication choices in juvenile rheumatoid arthritis II--update of a survey performed in 1993.

    PubMed

    Brunner, H I; Kim, K N; Ballinger, S H; Bowyer, S L; Griffin, T A; Higgins, G C; Mier, R; Passo, M H; Rennebohm, R; Schikler, K; Lovell, D J

    2001-10-01

    The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is important to allow for the evaluation of practice patterns for future outcome studies. A survey of nine pediatric rheumatologists was performed between September 1999 and February 2000. Each of the physicians prospectively recorded demographic and treatment information on consecutively sampled JRA patients (n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in 35%, and systemic onset JRA in 19% of the children. Naproxen was the most frequently prescribed medication (55% of the patients), followed by methotrexate (MTX), which was used in 39% of the patients. Folic acid supplementation (1 mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used in 11% of the children. Eleven percent of the patients received corticosteroids, and 13% of children on corticosteroids took calcium supplements. Uveitis was present in 8% and had a chronic course in 79% of those cases. Although systemic medications were used in 50% of the children with uveitis to control eye inflammation, severe damage to the eyes developed in 30% of them. Fourteen percent of the patients required gastroprotective medications. Compared with findings of a similar survey performed in 1993, there was no significant change in the frequency of use of naproxen, but nabumetone is now more often prescribed, and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among second-line agents used for JRA have also occurred, although there was no change in the frequency of use of MTX or corticosteroids. JRA continues to be a treatment challenge for the practicing pediatric rheumatologist. Patients often show incomplete response to the currently available medications. Therefore, new therapeutic agents need to be evaluated for their use in JRA, and the treatment of JRA associated uveitis especially needs to be improved. PMID:17039159

  15. Symptom Complexes at the Earliest Phases of Rheumatoid Arthritis: A Synthesis of the Qualitative Literature

    PubMed Central

    Stack, Rebecca J; Sahni, Melanie; Mallen, Christian D; Raza, Karim

    2013-01-01

    Objective Understanding the features and patterns of symptoms that characterize the earliest stages of rheumatoid arthritis (RA) is of considerable importance if patients are to be identified and started on treatment early. However, little is known about the characteristics of symptoms at the onset of a disease that eventually progresses to RA. Methods A systematic review of qualitative peer-reviewed publications was conducted to identify the earliest symptoms associated with the onset of RA. A total of 1,736 abstracts were searched to identify relevant publications. Twenty-six publications were identified, assessed for quality, and subjected to analysis informed by thematic and grounded theory frameworks. Results Several interacting themes describing the early symptoms of RA were identified, including swelling, pain and tenderness, stiffness, fatigue and weakness, and the emotional impact of symptoms. For each symptom, different and evolving intensities were described; in some cases, patterns of symptom onset and symptom complexes at the onset of RA were highlighted. Importantly, this review has emphasized major deficiencies in the literature. None of the studies reviewed originally aimed to explore symptoms at RA onset (often discussions about symptom onset were secondary to the study's primary aim). Also, many of the articles identified sampled people diagnosed with RA many years previously, making their recollection of symptoms at onset less reliable. Conclusion In order for clinicians to fully understand the earliest phases of disease, the nature of symptoms at onset needs to be understood. The current work represents a useful starting point, but this area needs further qualitative investigation, followed by quantitative explorations of symptom clusters and their associated features. PMID:23926091

  16. Pulmonary involvement in rheumatoid arthritis: A cross-sectional study in Iran

    PubMed Central

    Zayeni, Habib; Haji-Abbasi, Asghar; Foumani, Seyed Ali Alavi; Tohidi, Mehdi; Masooleh, Irandokht Shenavar; Parsa, Banafsheh Ghavidel; Aghaei, Mehrdad; Hassankhani, Amir; Parsa, Pooneh Ghavidel; Maafi, Alireza Amir

    2016-01-01

    Background: Interstitial lung disease (ILD) is a type of pulmonary manifestation in patients with rheumatoid arthritis (RA). Mostly RA-ILD has no symptoms and is only diagnosed by clinical examination, pulmonary function test (PFT), and high-resolution computed tomography (HRCT); hence it seems that the diagnosis of pulmonary involvement in early stages of RA is of great importance. Therefore, we decided to answer this question whether the evaluation of RA patients without pulmonary symptoms using methods such as PFT and HRCT are justifiable and reasonable or not. Methods: We conducted a cross-sectional study in a referral rheumatology clinic in Razi hospital of Rasht, Iran. Forty-four consecutive patients, diagnosed with RA, were enrolled. Physical examination of the joints was performed by an rheumatologist. The activity of RA was evaluated in all patients by Disease Activity Score 28. An expert pulmonologist performed the respiratory examination in all participants. Then, all subjects were referred for chest X-ray, PFT, and HRCT of lungs. Results: Patients included in this study, 9 (20.45%) males and 35 (79.55%) females, were 21–73 years old and their mean age was 49 ± 13 years. Significant relation between PFT and respiratory complaints was observed (P = 0.016). PFT had significant relation with respiratory examinations (P = 0.009). Our results indicated a significant relation between disease activity rate and PFT (P = 0.038). While HRCT had any significant relation with above items. Conclusion: We concluded, using PFT in the respiratory assessment of RA patients can be limited to persons with high disease activity, respiratory complaints, and positive findings in the clinical respiratory examination. PMID:26933307

  17. An algorithm to identify rheumatoid arthritis in primary care: a Clinical Practice Research Datalink study

    PubMed Central

    Muller, Sara; Hider, Samantha L; Raza, Karim; Stack, Rebecca J; Hayward, Richard A; Mallen, Christian D

    2015-01-01

    Objective Rheumatoid arthritis (RA) is a multisystem, inflammatory disorder associated with increased levels of morbidity and mortality. While much research into the condition is conducted in the secondary care setting, routinely collected primary care databases provide an important source of research data. This study aimed to update an algorithm to define RA that was previously developed and validated in the General Practice Research Database (GPRD). Methods The original algorithm consisted of two criteria. Individuals meeting at least one were considered to have RA. Criterion 1: ≥1 RA Read code and a disease modifying antirheumatic drug (DMARD) without an alternative indication. Criterion 2: ≥2 RA Read codes, with at least one ‘strong’ code and no alternative diagnoses. Lists of codes for consultations and prescriptions were obtained from the authors of the original algorithm where these were available, or compiled based on the original description and clinical knowledge. 4161 people with a first Read code for RA between 1 January 2010 and 31 December 2012 were selected from the Clinical Practice Research Datalink (CPRD, successor to the GPRD), and the criteria applied. Results Code lists were updated for the introduction of new Read codes and biological DMARDs. 3577/4161 (86%) of people met the updated algorithm for RA, compared to 61% in the original development study. 62.8% of people fulfilled both Criterion 1 and Criterion 2. Conclusions Those wishing to define RA in the CPRD, should consider using this updated algorithm, rather than a single RA code, if they wish to identify only those who are most likely to have RA. PMID:26700281

  18. Is rheumatoid arthritis in Indians associated with HLA antigens sharing a DR beta 1 epitope?

    PubMed Central

    Ollier, W E; Stephens, C; Awad, J; Carthy, D; Gupta, A; Perry, D; Jawad, A; Festenstein, H

    1991-01-01

    HLA class II antigens were identified in a group of 44 patients with rheumatoid arthritis (RA) originating largely from the north or northeast of the Indian subcontinent and resident now in east London. Compared with 67 locally typed east London Asian controls, the prevalence of three HLA-DR antigens was raised in the patients: DR1 18.2% v 6.0% chi 2 = 3.99, DR4 20.5% v 11.9% chi 2 = 1.48, and DRw10 27.3% v 8.9% chi 2 = 6.56. These differences were also found when the patients with RA were compared with a larger control group of 110 northern Indians: DR1 18.2% v 7.2% chi 2 = 4.02, DR4 20.5% v 7.2% chi 2 = 5.56, and DRw10 27.3% v 8.1% chi 2 = 9.7. Twenty five (57%) of the patients expressed at least one of these antigens. All patients were also characterised for HLA-Dw types by mixed lymphocyte culture typing. The prevalence of the HLA-DR4 associated Dw types in the patients was: Dw4 2.3%, Dw10 0%, Dw14 11.4%, and Dw15 6.8%. The DR beta 1 chains of DR1 and DRw10 together with the Dw types of DR4 other than Dw10 share amino acid residues in a region of the third hypervariable region considered to be critical in antigen presentation. It is concluded that RA in Indians is associated with these HLA antigens, and data from this study support the hypothesis of a cross reactive epitope common to HLA specificities associated with RA. PMID:1710441

  19. Opioid use in patients with rheumatoid arthritis 2005-2014: a population-based comparative study.

    PubMed

    Zamora-Legoff, Jorge A; Achenbach, Sara J; Crowson, Cynthia S; Krause, Megan L; Davis, John M; Matteson, Eric L

    2016-05-01

    Opioid prescriptions have seen an increase across the USA, Canada, Europe, and the UK. In the USA, they have quadrupled from 1999 to 2010. Opioid use among patients with rheumatoid arthritis (RA) over time is not well described. This study examined trends of opioid use in patients with RA. Retrospective prescription data was examined from 2005 to 2014 in a population-based incidence cohort of patients with RA by 1987 ACR criteria and comparable non-RA subjects. Differences in opioid use were examined with Poisson models. A total of 501 patients with RA (71 % female) and 532 non-RA subjects (70 % female) were included in the study. Total and chronic opioid use in 2014 was substantial in both cohorts 40 % RA vs 24 % non-RA and 12 % RA vs. 4 % non-RA, respectively. Opioid use increased by 19 % per year in both cohorts during the study period (95 % confidence interval [CI] 1.15, 1.25). Relative risk (RR) of chronic opiate use for RA patients compared to non-RA subjects was highest in adults aged 50-64 years (RR 2.82; 95 % CI 1.43-6.23). RA disease characteristics, biologic use at index, treated depression/fibromyalgia, education, and smoking status were not significantly associated with chronic opiate use. Over a third of patients with RA use opioids in some form, and in more than a tenth use is chronic. Use has increased in recent years. Patients aged 50-64 with RA use substantially more opioids than their non-RA counterparts. PMID:27022929

  20. The process of acceptance among rheumatoid arthritis patients in Switzerland: A qualitative study

    PubMed Central

    Kostova, Zlatina; Caiata-Zufferey, Maria; Schulz, Peter J

    2014-01-01

    BACKGROUND: Rheumatoid arthritis (RA) is a chronic, painful disease with many injurious psychological effects. Acceptance is an important component of pain management and is associated with improved quality of life, and lower levels of pain and depression. While studies have begun to identify the stages of acceptance, little is known about factors influencing the ease and speed with which patients pass through these stages. OBJECTIVE: To explore the main stages through which RA patients pass and the strategies they adopt to learn to live with the pain, and to identify factors shaping patients’ capacities to achieve acceptance. METHODS: A qualitative study involving 20 semistructured interviews with RA patients in the Italian-speaking region of Switzerland was conducted. Analysis of the data followed the precepts of grounded theory. RESULTS: Although the present study revealed that acceptance is not a smooth or linear process, five main stages in patients’ struggles to accommodate the newly imposed limitations were, nonetheless, identified: naming the illness; realizing the illness; resisting the illness; ‘hitting the bottom’; and integrating the illness. Diagnosis proved to be an especially tortuous stage in the case of RA, and the effects of delayed diagnosis continued to be felt during the subsequent stages. Patients’ understanding of the notion of acceptance and the strategies that they used to achieve it were also explored. CONCLUSIONS: Diagnosis of RA is notoriously difficult. Beyond the clinical difficulties, structural reasons for late diagnosis (symptoms being neglected by patients and medical professionals) were identifed. Delayed diagnosis hindered the acceptance process throughout, and led to more resistant behaviour and to a struggle to achieve the optimal formula for acceptance – accepting the losses of prepain life while still pursuing personal goals. PMID:24527466

  1. A descriptive, cross-sectional study characterizing bone erosions in rheumatoid arthritis and gout by ultrasound.

    PubMed

    Ventura-Ríos, Lucio; Hernández-Díaz, Cristina; Sanchez-Bringas, Guadalupe; Madrigal-Santillán, Eduardo; Morales-González, José Antonio; Pineda, Carlos

    2016-09-01

    The aim of this study is to characterize bone erosions in metatarsal heads (MTH) in rheumatoid arthritis (RA) and gout by grayscale ultrasound. In a descriptive, cross-sectional study, we evaluated 40 patients with RA and 40 with gout, both diagnosed according to the American College of Rheumatology/European League Against Rheumatism criteria, respectively. All patients had bone erosion demonstrated by ultrasound, which was used, following OMERACT criteria, to describe the shape, size, number, border definition, overhanging margin, topography (intra- or extra-articular), and distribution (over dorsal, medial, lateral, or plantar aspect) of the lesions in the MTH. Descriptive statistics were used and a concordance exercise between two ultrasonographers blinded to the diagnosis was performed. Bone erosions in RA were observed most frequently at the plantar and lateral aspect of the fifth MTH, round in 96 %, small-sized (2.43 ± 0.9 mm), intra-articular (100 %), and single (75 %). Few bone erosions had a well-defined border an overhanging margin while in gout were found most frequently in the medial and dorsal aspect of the first MTH, single in 71 %, intra-articular in 100 %, and of median size (4.0 ± 2.3). For shape, 51 % was round and 49 % was oval. A well-defined border was present in 39 %, and an overhanging margin in 62 %. Inter-rater reliability kappa was excellent (0.81, 95 % CI 0.56-1.00). Some characteristics of bone erosions in RA, including shape, size, ill-defined border, and localization in the fifth MTH could distinguish the lesions from gout. Grayscale US has excellent reliability to describe bone erosions in RA and gout. PMID:27393079

  2. Circulating interleukin-6 and rheumatoid arthritis

    PubMed Central

    Li, Bing; Xiao, Yu; Xing, Dan; Ma, Xin-long; Liu, Jun

    2016-01-01

    Abstract Interleukin-6 (IL-6), as a pleiotropic cytokine, has been demonstrated to be closely associated with the pathogenisis of rheumatoid arthritis (RA). However, whether this association is causal or not remains unclear, because of the multifactorial role of IL-6 and related confounding factors. We aimed to evaluate the causal relevance between circulating IL-6 levels and the risk of RA through meta-analytical Mendelian randomization approach. IL-6 gene -174G/C variant was selected as an instrument in this Mendelian randomization meta-analysis. Article identification and data collection were conducted in duplicate and independently by 2 authors. The STATA software was used for data analysis. In total, 15 and 5 articles on the association of the -174G/C variant with RA risk and circulating IL-6 level, respectively, were included. The overall analysis showed that C allelic and GC+CC genotype were significantly with 1.59-fold (95% CI: 1.19–2.14) and 1.63-fold (95% CI: 1.17–2.26) increased risk of developing RA, respectively. Asian populations showed stronger association with 4.55-fold (95% CI: 1.62–12.75), 1.84-fold (95% CI: 1.13–2.99), and 4.69-fold (95% CI: 1.68–13.14) increased RA risk in carriers of -174C allelic, CC, and GC+CC genotype, respectively. Carriers of GC+CC genotype showed significant reduction in the circulating IL-6 level compared with GG carriers (WMD = −0.77; 95% CI: −1.16 to −0.38; P = 0.000) in overall populations. Mendelian randomization presented 6% and 22% increased risk of RA with 0.1 pg/mL reduction of circulating IL-6 level in overall and Asian populations, respectively. This Mendelian randomization meta-analysis demonstrated that the long-term genetically reduced circulating IL-6 level might be causally related to a higher risk of RA, especially in Asian populations. PMID:27281095

  3. Body mass index and response to tocilizumab in rheumatoid arthritis: a real life study.

    PubMed

    Gardette, A; Ottaviani, S; Sellam, J; Berenbaum, F; Lioté, F; Meyer, A; Sibilia, J; Fautrel, B; Palazzo, E; Dieudé, P

    2016-04-01

    Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor α (anti-TNFα) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 ≥ 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0-28.8) kg/m(2). The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1-29.9] vs 24.9 [22.0-27.1], P = 0.38), EULAR good response (25.9 [22.8-30.0] vs 25.4 [22.0-28.4], P = 0.61), and remission (25.1 [22.5-28.6] vs 25.4 [22.0-28.9], P = 0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients. PMID:26801332

  4. Withdrawal of biologic agents in rheumatoid arthritis: a systematic review and meta-analysis.

    PubMed

    Galvao, Tais Freire; Zimmermann, Ivan Ricardo; da Mota, Licia Maria Henrique; Silva, Marcus Tolentino; Pereira, Mauricio Gomes

    2016-07-01

    The aim of this study is to assess the efficacy of withdrawing biologics from patients with rheumatoid arthritis in sustained remission or low disease activity. This is a systematic review of clinical trials that randomized withdrawal or continuation of biologics. We searched MEDLINE, Embase, and other databases. Three authors independently selected and extracted the data from the studies. The GRADE approach was employed to assess the quality of the evidence. We calculated meta-analyses of random effects model and estimated the heterogeneity by I (2). The number needed to treat (NNT) was calculated for significant outcomes. We included six trials (N = 1927 patients), most were industry-sponsored. Compared to withdrawing, continuing biologics increased the probability of low disease activity (relative risk [RR] = 0.66, 95 % CI 0.51-0.84, I (2) = 91 %, NNT = 4, low quality), remission (0.57, 0.44-0.74, I (2) = 82 %, NNT = 3, low quality), and radiographic progression (RR = 0.91, 95 % CI 0.85-0.98, I (2) = 13 %, NNT = 12, moderate quality). No significant difference was detected in the incidence of serious adverse events, serious infection, malignancy, and scores of improvement of tender and swollen joints between these strategies (low quality). A worse profile of outcomes was experienced by those patients when compared to the ones that continued biologics, but almost half of patients maintained low disease activity after withdrawal. As the quality of evidence was low, the conclusions may change as new results become available. The potential harms and benefits of this decision must be discussed with patients. PMID:27107756

  5. Hepatitis B virus reactivation in a juvenile rheumatoid arthritis patient under treatment and its successful management: a complicated case.

    PubMed

    Durmus, Oguz; Tekin, Levent; Carli, Alparslan Bayram; Cakar, Engin; Acar, Ali; Ulcay, Asim; Dincer, Umit; Kiralp, Mehmet Zeki

    2013-05-01

    Juvenile rheumatoid arthritis is a common chronic inflammatory disease in the childhood and it can differentiate rarely into spondiloarthropaties. It is one of the important causes of chronic pain and disability. Some of the drugs used for the treatment have immunosupressive activity. One of the serious side-effects of immunosupressive treatment is activation of opportunistic pathogens. Hepatitis B virus (HBV) is one of these pathogens, and the rate of carriers in the population is considerably high. It can cause liver damage and death if reactivated. Thus, the management of oppotunistic pathogens becomes a complex issue when treating rheumatic diseases with immunosupressive drugs. In this case report, we present a juvenile rheumatoid arthritis patient whose liver enzymes raised while he was under treatment and afterwards HBV reactivation was determined as the cause. When reactivation was detected, we started controlled antiviral therapy. We achieved successful clinical and laboratory results after adding biological agents to the treatment. Careful evaluation of the patients who have indication for immunosuppressive agents and regular follow-up in case of infection may be protective from severe morbidity and/or mortality. PMID:22147111

  6. Rheumatoid Arthritis Disadvantages Younger Patients for Cardiovascular Diseases: A Meta-Analysis

    PubMed Central

    Fransen, Jaap; Kazemi-Bajestani, Seyyed M. R.; Bredie, Sebastian J. H.; Popa, Calin D.

    2016-01-01

    Introduction The incidence of cardiovascular diseases (CVD) is increased in rheumatoid arthritis (RA) patients. It remains unclear whether the load of RA increases cardiovascular (CV) risk especially in female and in younger RA patients. In the present study we aim to analyse the influence of age and gender on CV risk in RA relative to the general population, using meta-analysis of direct comparative studies. Method Systematic literature search was performed in MEDLINE for studies reporting on occurrence of CV events in RA as compared to the general population, stratified for gender and/or age. Quality was appraised using the Newcastle-Ottawa scale. Meta-analysis was performed on rate ratios using inverse variance methods. Results There were 1372 records screened and 13 studies included. RA females and males have a similar higher risk (95%CI) to develop stroke with RR 1.35 (1.30–1.40) and RR 1.31 (1.21–1.43); coronary artery disease with RR 1.65 (1.54–1.76) versus RR 1.55 ((1.41–1.69) in men; cardiovascular disease with RR 1.56 (1.49–1.62) versus 1.50 (1.41–1.60). The highest incidence of CV events was observed in the youngest patients, RR 2.59 (1.77–3.79), whereas older patients had the lowest relative risk when compared to the general population, RR 1.27 (1.16–1.38). Conclusion The relative risk of RA patients for CVD is age dependent, but does not depend on gender: the relative risk on CVD appears to be equally raised for males and females, while relatively young RA patients (<50 years) have the highest, and older patients the lowest relative risk. PMID:27310259

  7. A case series to describe the clinical characteristics of foot ulceration in patients with rheumatoid arthritis.

    PubMed

    Siddle, Heidi J; Firth, Jill; Waxman, Robin; Nelson, E Andrea; Helliwell, Philip S

    2012-03-01

    The aim of this study was to describe the clinical characteristics of foot ulceration in patients with rheumatoid arthritis (RA). Adults with RA and current foot ulceration but without diabetes were recruited. Clinical examination included assessment of RA disease activity, foot deformity, peripheral vascular disease, neuropathy and plantar pressures. Location, wound characteristics and time to healing were recorded for each ulcer. Participants completed the Health Assessment Questionnaire and Leeds Foot Impact Scale. Thirty-two cases with 52 current ulcers were recruited. Thirteen patients (41%) experienced more than one current ulcer: 5 (16%) had bilateral ulceration, 15 (47%) had previous ulceration at a current ulcer site. The majority (n = 33) of open ulcers were located over the dorsal aspect of the interphalangeal joints (n = 12), plantar aspect of the metatarsophalangeal joints (MTPJs) (n = 12) and medial aspect of first MTPJs (n = 9). In ulcerated limbs (n = 37), ankle brachial pressure index (ABPI) was <0.8 in 2 (5%); protective sensation was reduced in 25 (68%) and peak plantar pressures were >6 kg/cm(2) in 6 (16%). Mean ulcer size was 4.84 by 3.29 mm. Most ulcers (n = 42, 81%) were superficial; five (9.6%) were infected. Time to healing was available for 41 ulcers: mean duration was 28 weeks. Three ulcers remained open. In conclusion, foot ulceration in RA is recurrent and multiple ulcers are common. Whilst ulcers are small and shallow, time to achieve healing is slow, posing infection risk. Reduced protective sensation is common in affected patients. The prevalence of arterial disease is low but may be under estimated due to high intolerance of ABPI. PMID:22052587

  8. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis.

    PubMed

    Tracy, T S; Krohn, K; Jones, D R; Bradley, J D; Hall, S D; Brater, D C

    1992-01-01

    We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations. PMID:1618240

  9. Expression and functional role of 1F7 (CD26) antigen on peripheral blood and synovial fluid T cells in rheumatoid arthritis patients.

    PubMed

    Muscat, C; Bertotto, A; Agea, E; Bistoni, O; Ercolani, R; Tognellini, R; Spinozzi, F; Cesarotti, M; Gerli, R

    1994-11-01

    The expression and the functional role of the CD26 (1F7) T cell surface molecule, an ectoenzyme which seems to represent a functional collagen receptor of T lymphocytes and to have a role in T cell activation, were analysed in both peripheral blood (PB) and synovial fluid (SF) T cell samples from patients with active and inactive rheumatoid arthritis (RA). Although patients with active disease displayed higher percentages of PB CD26+ CD4+ T cells than inactive RA and control subjects, CD26 antigen expression on RA SF T lymphocytes was low. The anti-1F7 binding to the T cell surface, that led to CD26 antigen modulation and enhancement of both IL-2 synthesis by, and 3H-TdR incorporation of, anti-CD3- or anti-CD2-triggered PB T cells in RA and control subjects, was unable to affect significantly both expression and functional activity of RA SF T lymphocytes. Since the 1F7 antigen spontaneously reappeared on the surface of unstimulated SF T cells after 2-5 days of culturing, the low 1F7 antigen expression of anti-1F7 in the SF T cell compartment may be the result of in vivo molecule modulation exerted by the natural ligand in the joint, with important implications for T cell activation and lymphokine synthesis. PMID:7955530

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

    PubMed Central

    Manriquez, Juan; Giesen, Laura; del Puerto, Constanza; 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. PMID:27579747

  11. Functional analysis of the p53 codon 72 polymorphism in black South Africans with rheumatoid arthritis--a pilot study.

    PubMed

    Moodley, Devapregasan; Mody, Girish M; Chuturgoon, Anil A

    2010-10-01

    The p53 tumor-suppressor protein plays an integral role in apoptosis. Perturbations in peripheral lymphocyte (PL) apoptosis may be associated with rheumatoid arthritis (RA). Polymorphisms at codon 72 of p53 (arginine (Arg72) to proline transition) confers differences in mitochondrial translocation and apoptosis inducing capabilities of p53 in vitro. We examined associations of this polymorphism with PL apoptosis, mitochondrial depolarization, and clinical markers of disease activity in a cohort of black South African RA patients. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. PL apoptosis was measured using the annexin-V assay and mitochondrial membrane potential with the JC-1 assay. Clinical and laboratory parameters were recorded for all patients. Statistical differences in these parameters were investigated according to genotype. Genotype distribution did not differ significantly between RA patients and controls (Arg/Arg, Arg/Pro, Pro/Pro: 12%, 46%, and 42% versus 3%, 34%, and 63%), despite significantly higher frequency of the Arg72 allele in patients (p = 0.0406). There was no significant difference in PL apoptosis and mitochondrial depolarization based on p53 codon 72 genotype. In addition, clinical markers of disease activity were not significantly different between genotypes. We conclude that p53 codon 72 genotype does not influence PL apoptosis or mitochondrial depolarization and is not associated with clinical markers of disease in RA. PMID:20532936

  12. The molecular mechanism of osteoclastogenesis in rheumatoid arthritis

    PubMed Central

    Udagawa, Nobuyuki; Kotake, Shigeru; Kamatani, Naoyuki; Takahashi, Naoyuki; Suda, Tatsuo

    2002-01-01

    Bone-resorbing osteoclasts are formed from hemopoietic cells of the monocyte–macrophage lineage under the control of bone-forming osteoblasts. We have cloned an osteoblast-derived factor essential for osteoclastogenesis, the receptor activator of NF-κB ligand (RANKL). Synovial fibroblasts and activated T lymphocytes from patients with rheumatoid arthritis also express RANKL, which appears to trigger bone destruction in rheumatoid arthritis as well. Recent studies have shown that T lymphocytes produce cytokines other than RANKL such as IL-17, granulocyte–macrophage colony-stimulating factor and IFN-γ, which have powerful regulatory effects on osteoclastogenesis. The possible roles of RANKL and other cytokines produced by T lymphocytes in bone destruction are described. PMID:12223101

  13. Endothelial Dysfunction and Inflammation: Immunity in Rheumatoid Arthritis

    PubMed Central

    Yang, XueZhi; Chang, Yan; Wei, Wei

    2016-01-01

    Inflammation, as a feature of rheumatoid arthritis (RA), leads to the activation of endothelial cells (ECs). Activated ECs induce atherosclerosis through an increased expression of leukocyte adhesion molecules. Endothelial dysfunction (ED) is recognized as a failure of endothelial repair mechanisms. It is also an early preclinical marker of atherosclerosis and is commonly found in RA patients. RA is now established as an independent cardiovascular risk factor, while mechanistic determinants of ED in RA are still poorly understood. An expanding body of study has shown that EC at a site of RA is both active participant and regulator of inflammatory process. Over the last decade, a role for endothelial dysfunction in RA associated with cardiovascular disease (CVD) has been hypothesized. At the same time, several maintenance drugs targeting this phenomenon have been tested, which has promising results. Assessment of endothelial function may be a useful tool to identify and monitor RA patients. PMID:27122657

  14. Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study

    PubMed Central

    Zheng, Guifeng; Zou, Hai; Wang, Jian Min; Lin, Yao Yao; Chuka, Chifundo Martha; Ge, Ren Shan; Zhai, Weitao; Wang, Jian Guang

    2015-01-01

    Objectives To explore the pathogenesis of rheumatoid arthritis (RA), the different metabolites were screened in synovial fluid by metabolomics. Methods Synovial fluid from 25 RA patients and 10 normal subjects were analyzed by GC/TOF MS analysis so as to give a broad overview of synovial fluid metabolites. The metabolic profiles of RA patients and normal subjects were compared using multivariate statistical analysis. Different proteins were verified by qPCR and western blot. Different metabolites were verified by colorimetric assay kit in 25 inactive RA patients, 25 active RA patients and 20 normal subjects. The influence of hypoxia-inducible factor (HIF)-1α pathway on catabolism was detected by HIF-1α knockdown. Results A subset of 58 metabolites was identified, in which the concentrations of 7 metabolites related to energy metabolism were significantly different as shown by importance in the projection (VIP) (VIP≥1) and Student’s t-test (p<0.05). In the 7 metabolites, the concentration of glucose was decreased, and the concentration of lactic acid was increased in the synovial fluid of RA patients than normal subjects verified by colorimetric assay Kit. Receiver operator characteristic (ROC) analysis shows that the concentration of glucose and lactic acid in synovial fluid could be used as dependable biomarkers for the diagnosis of active RA, provided an AUC of 0.906 and 0.922. Sensitivity and specificity, which were determined by cut-off points, reached 84% and 96% in sensitivity and 95% and 85% in specificity, respectively. The verification of different proteins identified in our previous proteomic study shows that the enzymes of anaerobic catabolism were up-regulated (PFKP and LDHA), and the enzymes of aerobic oxidation and fatty acid oxidation were down-regulated (CS, DLST, PGD, ACSL4, ACADVL and HADHA) in RA patients. The expression of HIF-1α and the enzymes of aerobic oxidation and fatty acid oxidation were decreased and the enzymes of anaerobic

  15. Optical monitoring of rheumatoid arthritis: Monte Carlo generated reconstruction kernels

    NASA Astrophysics Data System (ADS)

    Minet, O.; Beuthan, J.; Hielscher, A. H.; Zabarylo, U.

    2008-06-01

    Optical imaging in biomedicine is governed by the light absorption and scattering interaction on microscopic and macroscopic constituents in the medium. Therefore, light scattering characteristics of human tissue correlate with the stage of some diseases. In the near infrared range the scattering event with the coefficient approximately two orders of magnitude greater than absorption plays a dominant role. When measuring the optical parameters variations were discovered that correlate with the rheumatoid arthritis of a small joint. The potential of an experimental setup for transillumination the finger joint with a laser diode and the pattern of the stray light detection are demonstrated. The scattering caused by skin contains no useful information and it can be removed by a deconvolution technique to enhance the diagnostic value of this non-invasive optical method. Monte Carlo simulations ensure both the construction of the corresponding point spread function and both the theoretical verification of the stray light picture in rather complex geometry.

  16. Molecular Insight into Gut Microbiota and Rheumatoid Arthritis

    PubMed Central

    Wu, Xiaohao; He, Bing; Liu, Jin; Feng, Hui; Ma, Yinghui; Li, Defang; Guo, Baosheng; Liang, Chao; Dang, Lei; Wang, Luyao; Tian, Jing; Zhu, Hailong; Xiao, Lianbo; Lu, Cheng; Lu, Aiping; Zhang, Ge

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, and RA. It has become known that gut microbiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gut microbiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA. PMID:27011180

  17. Extra-articular Manifestations in Rheumatoid Arthritis

    PubMed Central

    Cojocaru, Manole; Cojocaru, Inimioara Mihaela; Silosi, Isabela; Vrabie, Camelia Doina; Tanasescu, R

    2010-01-01

    ABSTRACT Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main characteristic is persistent joint inflammation that results in joint damage and loss of function. Although RA is more common in females, extra-articular manifestations of the disease are more common in males. The extra-articular manifestations of RA can occur at any age after onset. It is characterised by destructive polyarthritis and extra-articular organ involvement, including the skin, eye, heart, lung, renal, nervous and gastrointestinal systems. The frequence of extra-articular manifestations in RA differs from one country to another. Extra-articular organ involvement in RA is more frequently seen in patients with severe, active disease and is associated with increased mortality. Incidence and frequence figures for extra-articular RA vary according to study design. Extra-articular involvement is more likely in those who have RF and/or are HLA-DR4 positive. Occasionally, there are also systemic manifestations such as vasculitis, visceral nodules, Sjögren's syndrome, or pulmonary fibrosis present. Nodules are the most common extra-articular feature, and are present in up to 30%; many of the other classic features occur in 1% or less in normal clinic settings. Sjögren's syndrome, anaemia of chronic disease and pulmonary manifestations are relatively common – in 6-10%, are frequently present in early disease and are all related to worse outcomes measures of rheumatoid disease in particular functional impairment and mortality. The occurrence of these systemic manifestations is a major predictor of mortality in patients with RA. This paper focuses on extra-articular manifestations, defined as diseases and symptoms not directly related to the locomotor system. PMID:21977172

  18. Lymphotoxin α revisited: general features and implications in rheumatoid arthritis

    PubMed Central

    2011-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting synovial joints. Therapies blocking tumor necrosis factor-alpha (TNFα) are now routinely used in the management of RA. However, a significant number of patients with RA do not respond or develop resistance to anti-TNF therapies, and the participation of other cytokines in RA pathogenesis has been reported as well. Lymphotoxin alpha (LTα) is the closest homolog to TNFα and has been implicated in inflammation and autoimmunity since its original description in 1968. In spite of that, little is known about the role of LTα in RA or the potential of blocking this cytokine as an alternative therapeutic approach. In this review, we aim to summarize the general features of LTα and what is currently known about its participation in RA. PMID:21861866

  19. Prospective study of the clinical value of determining circulating IgA-alpha 1-antitrypsin complex using a prototype ELISA kit in patients with rheumatoid arthritis.

    PubMed Central

    Iwana, K; Aotsuka, S; Nishioka, K

    1996-01-01

    OBJECTIVE: To evaluate the clinical value of determining circulating IgA-alpha 1-antitrypsin (IgA-AT) complex in rheumatoid arthritis. METHODS: The IgA-AT complex was assayed by a prototype ELISA kit using a specific monoclonal antibody against the complex. RESULTS: The median level of serum IgA-AT complex in rheumatoid patients (2.26 AU ml-1) was significantly higher than in osteoarthritis patients (1.37 AU ml-1, P < 0.05) and healthy volunteers (1.03 AU ml-1, P < 0.001). The concentration of IgA-AT complex in rheumatoid arthritis patients at baseline was correlated with the number of painful joints (P < 0.05), number of swollen joints (P < 0.01), erythrocyte sedimentation rate (P < 0.05), and modified Lansbury index (P < 0.01). The median serum level of IgA-AT complex in rheumatoid patients at baseline was higher than that at three months (P < 0.01), six months (P < 0.01), and 12 months (P < 0.01) after the start of treatment. The difference and ratio of IgA-AT complex levels before and after treatment were significantly associated with radiographic progression. CONCLUSIONS: The findings validate the usefulness of determining IgA-AT complex using ELISA in the management of rheumatoid arthritis. PMID:8976645

  20. 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

  1. Biosimilars for the management of rheumatoid arthritis: economic considerations.

    PubMed

    Gulácsi, László; Brodszky, Valentin; Baji, Petra; Kim, HoUng; Kim, Su Yeon; Cho, Yu Young; Péntek, Márta

    2015-01-01

    Biologic drugs have proved highly effective for the treatment of immune-mediated inflammatory diseases such as rheumatoid arthritis (RA). These drugs are often considered cost-effective for well-defined RA patient populations not responding adequately to conventional treatment, but are used first-line relatively rarely, partly due to high costs. Furthermore, not all clinically eligible patients can access biologics even as second-line therapy. Recently, there has been a rise in interest in 'biosimilar' drugs that are highly comparable to the 'reference medicinal product' (RMP) in terms of efficacy and safety but may generally be lower in price. This review summarizes the cost burden of RA and considers the potential role of biosimilars in reducing drug costs and increasing patient access to biologics. PMID:26395836

  2. Tocilizumab-induced psoriasiform rash in rheumatoid arthritis.

    PubMed

    Palmou-Fontana, Natalia; Sánchez Gaviño, Juan Antonio; McGonagle, Dennis; García-Martinez, Eva; Iñiguez de Onzoño Martín, Luis

    2014-01-01

    Tocilizumab (TCZ) is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and has been approved for the treatment of rheumatoid arthritis (RA) patients who have had an inadequate response to previous biological therapies. Psoriasiform skin lesions, especially palmoplantar pustulosis lesions, are well described following anti-tumour necrosis factor therapy. We describe a 79-year-old woman with rheumatoid factor-positive, anti-citrullinated protein antibody-positive erosive RA, who developed a psoriasiform palmoplantar pustulosis reaction following treatment with TCZ therapy (IL-6 receptor). The rash showed histological features compatible with psoriasis and disappeared following discontinuation of TCZ. PMID:24942661

  3. Hyaluronan nanoparticles bearing γ-secretase inhibitor: in vivo therapeutic effects on rheumatoid arthritis.

    PubMed

    Heo, Roun; Park, Jong-Sung; Jang, Hye Jin; Kim, Seol-Hee; Shin, Jung Min; Suh, Yung Doug; Jeong, Ji Hoon; Jo, Dong-Gyu; Park, Jae Hyung

    2014-10-28

    γ-Secretase inhibitors which prevent Notch activation are emerging as potent therapeutics for various inflammatory diseases, including ischemic stroke and rheumatoid arthritis. However, their indiscriminate distribution in the body causes serious side effects after systemic administration, since Notch proteins are ubiquitous receptors that play an important role in cellular functions such as differentiation, proliferation, and apoptosis. In this study, hyaluronan nanoparticles (HA-NPs) bearing a γ-secretase inhibitor (DAPT) were prepared as potential therapeutics for rheumatoid arthritis. In vivo biodistribution of the DAPT-loaded HA-NPs (DNPs), labeled with near-infrared dye, were observed using a non-invasive optical imaging system after systemic administration to a collagen-induced arthritis (CIA) mouse model. The results demonstrated that DNPs were effectively accumulated at the inflamed joint of the CIA mice. From the in vivo therapeutic efficacy tests, DNPs (1mg DAPT/kg) significantly attenuated the severity of RA induction compared to DAPT alone (2mg/kg), which was judged from clinical scores, tissue damage, and neutrophil infiltration. In addition, DNPs dramatically reduced the production of pro-inflammatory cytokines (TNF-α, IFN-γ, MCP-1, and IL-6, -12, -17) and collagen-specific auto-antibodies (IgG1 and IgG2a) in the serum of the CIA mice. These results suggest that DNPs have potential as therapeutics for rheumatoid arthritis. PMID:25109660

  4. Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Maher, Jason R.; Takahata, Masahiko; Awad, Hani A.; Berger, Andrew J.

    2011-08-01

    Although glucocorticoids are frequently prescribed for the symptomatic management of inflammatory disorders such as rheumatoid arthritis, extended glucocorticoid exposure is the leading cause of physician-induced osteoporosis and leaves patients at a high risk of fracture. To study the biochemical effects of glucocorticoid exposure and how they might affect biomechanical properties of the bone, Raman spectra were acquired from ex vivo tibiae of glucocorticoid- and placebo-treated wild-type mice and a transgenic mouse model of rheumatoid arthritis. Statistically significant spectral differences were observed due to both treatment regimen and mouse genotype. These differences are attributed to changes in the overall bone mineral composition, as well as the degree of phosphate mineralization in tibial cortical bone. In addition, partial least squares regression was used to generate a Raman-based prediction of each tibia's biomechanical strength as quantified by a torsion test. The Raman-based predictions were as accurate as those produced by microcomputed tomography derived parameters, and more accurate than the clinically-used parameter of bone mineral density. These results suggest that Raman spectroscopy could be a valuable tool for monitoring bone biochemistry in studies of bone diseases such as osteoporosis, including tests of drugs being developed to combat these diseases.

  5. Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis

    PubMed Central

    Machado, Marina Amaral de Ávila; de Moura, Cristiano Soares; Ferré, Felipe; Bernatsky, Sasha; Rahme, Elham; Acurcio, Francisco de Assis

    2016-01-01

    ABSTRACT OBJECTIVE To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). METHODS This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients’ chances of persisting in their therapies after the first and after the two first years of follow-up. RESULTS The study included 11,642 patients with rheumatoid arthritis – 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD – and 1,251 patients with ankylosing spondylitis – 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. CONCLUSIONS A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing

  6. Arthritis of the Wrist

    MedlinePlus

    ... is caused by just two types: osteoarthritis and rheumatoid arthritis. Osteoarthritis Osteoarthritis (OA) is a progressive condition that ... other, it results in pain, stiffness, and weakness. Rheumatoid Arthritis Rheumatoid arthritis (RA) is a chronic disease that ...

  7. A medium-term follow-up study of 44 Souter-Strathclyde elbow arthroplasties carried out for rheumatoid arthritis.

    PubMed

    Dainton, Jeremy N; Hutchins, Philip M

    2002-01-01

    The results of 44 primary Souter-Strathclyde total elbow arthroplasties performed on 36 patients with rheumatoid arthritis are reported, with a mean follow-up of 6 years (range, 17 months-12 years; median, 6 years). Of these patients, 63% reported complete freedom from pain in the elbow, 25% mild intermittent pain, and 12% moderate pain. The mean range of motion at follow-up was 97 degrees (range, 40 degrees -135 degrees ). This represented a mean gain of 16.5 degrees of flexion, but only a 1.5 degrees gain in extension. Twenty-sevenelbows had a range of motion of 100 degrees or greater compared with 13 before surgery. There was 1 permanent ulnar nerve palsy and 1 deep infection requiring debridement. Six cases (4%) required revision, 2 for olecranon fractures and 4 for loosening. In patients with rheumatoid arthritis with low functional demand, the Souter-Strathclyde total elbow arthroplasty performs well in abolishing pain and increasing independence in carrying out the activities of daily living. PMID:12378169

  8. Social aspects of living with rheumatoid arthritis: a qualitative descriptive study in Soweto, South Africa – a low resource context

    PubMed Central

    Schneider, Marguerite; Manabile, Esther; Tikly, Mohammed

    2008-01-01

    Background Rheumatoid Arthritis (RA) is a chronic illness with important functional, social and employment consequences. We therefore undertook a cross-sectional study, using the International Classification of Functioning, Disability and Health framework, to investigate the personal and social consequences of RA in women, living under largely impoverished conditions. Methods A qualitative case study design was used with a convenience sample of 60 women with RA living in Soweto, South Africa. Semi-structured in-depth interviews were conducted to cover a range of experiences including onset of disease, treatment, environmental barriers and facilitators, employment, and social inclusion in family and community life. The outcomes are described according the International Classification of Functioning, Health and Disability framework at the body, person and societal levels and looking at both personal and environmental factors. Results The main features of living with RA were pain, muscle stiffness at the body level, difficulties in doing various activities such as mobility, washing, dressing, domestic activities, using transport and obtaining and maintaining employment at the person level. At the societal level the participants described difficulties moving around, interacting socially and taking part in community activities, fulfilling social roles and earning a living. Environmental facilitators such as assistive devices and health care services improved functioning. Barriers such as physical environments, lack of transport and basic services, such as electricity, and attitudes of others lead to social exclusion, loss of a sense of self and independence. Low income, lack of sufficient public transport, and sparse basic services were poverty features that exacerbated negative experiences. Conclusion The experiences of living with RA in a low resource context are similar to those in mid- and high resource contexts, but are exacerbated by poverty and the lack of basic

  9. Protective Role of the Interleukin 33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Rheumatoid Arthritis Patients

    PubMed Central

    Robustillo-Villarino, Montserrat; García-Bermúdez, Mercedes; Llorca, Javier; Corrales, Alfonso; González-Juanatey, Carlos; Ubilla, Begoña; Miranda-Filloy, José A.; Mijares, Verónica; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J.; Ramírez Huaranga, Marco A.; Mínguez Sánchez, María D.; Tejera Segura, Beatriz; Ferraz-Amaro, Iván; Vicente, Esther; Carmona, F. David; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A.

    2015-01-01

    Objectives To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Methods A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US). Results RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed. Conclusions In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA. PMID:26571131

  10. Preclinical lung disease in early rheumatoid arthritis.

    PubMed

    Robles-Perez, Alejandro; Luburich, Patricio; Rodriguez-Sanchon, Benigno; Dorca, Jordi; Nolla, Joan Miquel; Molina-Molina, Maria; Narvaez-Garcia, Javier

    2016-02-01

    Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lung disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lung disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels. PMID:26846584

  11. Efficacy of biological agents administered as monotherapy in rheumatoid arthritis: a Bayesian mixed-treatment comparison analysis

    PubMed Central

    Migliore, Alberto; Bizzi, Emanuele; Egan, Colin Gerard; Bernardi, Mauro; Petrella, Lea

    2015-01-01

    Background Biological agents provide an important therapeutic alternative for rheumatoid arthritis patients refractory to conventional disease-modifying antirheumatic drugs. Few head-to-head comparative trials are available. Purpose The aim of this meta-analysis was to compare the relative efficacy of different biologic agents indicated for use as monotherapy in rheumatoid arthritis. Methods A systemic literature search was performed on electronic databases to identify articles reporting double-blind randomized controlled trials investigating the efficacy of biologic agents indicated for monotherapy. Efficacy was assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria at 16–24 weeks. Relative efficacy was estimated using Bayesian mixed-treatment comparison models. Outcome measures were expressed as odds ratio and 95% credible intervals. Results Ten randomized controlled trials were selected for data extraction and analysis. Mixed-treatment comparison analysis revealed that tocilizumab offered 100% probability of being the best treatment for inducing an ACR20 response versus placebo, methotrexate, adalimumab, or etanercept. Likewise, for ACR50 and ACR70 outcome responses, tocilizumab had a 99.8% or 98.7% probability of being the best treatment, respectively, compared to other treatments or placebo. Tocilizumab increased the relative probability of being the best treatment (vs methotrexate) by 3.2-fold (odds ratio: 2.1–3.89) for all ACR outcomes. Conclusion Tocilizumab offered the greatest possibility of obtaining an ACR20, ACR50, and ACR70 outcome vs other monotherapies or placebo. PMID:26366085

  12. Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthritis.

    PubMed

    Whang, Jennifer A; Chang, Betty Y

    2014-08-01

    The function and role of Bruton's tyrosine kinase (BTK) in human B cell development was demonstrated by its association with X-linked agammaglobulinemia (XLA) manifested by a substantial reduction in immunoglobulins and B cells. BTK has a crucial role in pre-B cell receptor (BCR) and BCR signaling during normal B cell development and activation. Aberrant BCR signaling is associated with autoimmune diseases, such as rheumatoid arthritis (RA). In addition, BTK is also expressed in myeloid cell populations, including monocytes, macrophages, neutrophils and mast cells. These innate cells infiltrate the synovial cavity and produce inflammatory cytokines, aggravating arthritic symptoms. In myeloid cell populations, BTK functions downstream of the Fcγ receptors (FcγR) and Fcɛ receptors (FcɛR). In the absence of BTK, FcR-mediated functions, such as cytokine production, are impaired. In addition, Xid mice, which have a mutation in BTK, have decreased susceptibility to developing collagen-induced arthritis (CIA). Given that BTK is involved in multiple signaling pathways downstream of the BCR and FcR, it is an attractive therapeutic target for RA. PMID:24721226

  13. Smoking is a major preventable risk factor for Rheumatoid arthritis Estimations of risks after various exposures to cigarette smoke

    PubMed Central

    Källberg, Henrik; Ding, Bo; Padyukov, Leonid; Bengtsson, Camilla; Rönnelid, Johan; Klareskog, Lars; Alfredsson, Lars

    2011-01-01

    Background Earlier studies have demonstrated that smoking and genetic risk factors interact in providing an increased risk for Rheumatoid Arthritis (RA). Less is known on how smoking contributes to RA in the context of genetic variability, and what proportion of RA that may be caused by smoking. Objectives To determine the association between amount of smoking and risk of RA in the context of different HLA-DRB1 shared epitope (SE) alleles, and to estimate proportions of RA cases attributed to smoking. Design, Setting, and Participants Data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) case-control study encompassing 1204 cases and 871 controls were analysed. Main Outcome Measure Estimated odds ratio to develop RA and excess fraction of cases attributable to smoking according to amount of smoking and genotype. Results Smoking was estimated to be responsible for 35 % of the ACPA+ cases. For each HLA-DRB1 SE genotype, smoking was dose-dependently associated with increased risk of ACPA+ RA (p-trend<0.001). In individuals carrying two copies of the HLA-DRB1 shared epitope, 55 % of ACPA-positive RA were attributable to smoking. Conclusions Smoking is a preventable risk factor for RA. The increased risk due to smoking is dependent on amount of smoking and genotype. PMID:21149499

  14. Prevention of Stroke in Rheumatoid Arthritis.

    PubMed

    Zha, Alicia M; Di Napoli, Mario; Behrouz, Réza

    2015-12-01

    The risk of cerebrovascular disease is increased among rheumatoid arthritis (RA) patients and remains an underserved area of medical need. Only a minor proportion of RA patients achieve suitable stroke prevention. Classical cardiovascular risk factors appear to be under-diagnosed and undertreated among patients with RA. Reducing the inflammatory burden is also necessary to lower the cardiovascular risk. An adequate control of disease activity and cerebrovascular risk assessment using national guidelines should be recommended for all patients with RA. For patients with a documented history of cerebrovascular or cardiovascular risk factors, smoking cessation and corticosteroids and non-steroidal anti-inflammatory drugs at the lowest dose possible are crucial. Risk score models should be adapted for patients with RA by introducing a 1.5 multiplication factor, and their results interpreted to appropriately direct clinical care. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers are preferred treatment options. Biologic and non-biologic disease-modifying anti-rheumatic drugs should be initiated early to mitigate the necessity of symptom control drugs and to achieve early alleviation of the inflammatory state. Early control can improve vascular compliance, decrease atherosclerosis, improve overall lipid and metabolic profiles, and reduce the incidence of heart disease that may lead to atrial fibrillation. In patients with significant cervical spine involvement, early intervention and improved disease control are necessary and may prevent further mechanical vascular injury. PMID:26486791

  15. Janus kinase inhibitors for rheumatoid arthritis.

    PubMed

    Yamaoka, Kunihiro

    2016-06-01

    Treatment of autoimmune diseases, such as rheumatoid arthritis (RA), has advanced substantially over the past decade with the development of biologics targeting inflammatory cytokines. Recent progress in treating RA has been achieved with janus kinase (JAK) inhibitors (Jakinibs), an orally available disease-modifying anti-rheumatic drug targeting the intracellular kinase JAK and with similar efficacy to biologics. The first Jakinib approved for RA was tofacitinib, which exerted superiority to methotrexate and non-inferiority to tumor necrosis factor (TNF) inhibitors. In recent years, the Jakinib baricitinib has demonstrated superiority to both methotrexate and a TNF inhibitor, adalimumab. Given these promising findings, Jakinibs are expected to represent the next generation compounds for treating RA, and a number of Jakinibs are currently in clinical trials. Jakinibs can differ substantially in their selectivity against JAKs; tofacitinib and baricitinib target multiple JAKs, whereas the most recently developed Jakinibs target only a single JAK. The influence of Jakinib selectivity on efficacy and side effects is of great interest, requiring further careful observation. PMID:26994322

  16. Fucosyltransferase 1 mediates angiogenesis in rheumatoid arthritis

    PubMed Central

    Isozaki, Takeo; Amin, Mohammad A.; Ruth, Jeffrey H.; Campbell, Phillip L.; Tsou, Pei-Suen; Ha, Christine M.; Stinson, W. Alex; Domino, Steven E.; Koch, Alisa E.

    2015-01-01

    Objective The aim of this study was to determine the role of α(1,2)-linked fucosylation of proteins by fucosyltransferase1 (fut1) in rheumatoid arthritis (RA) angiogenesis. Methods Analysis of α(1,2)-linked fucosylated proteins in synovial tissues (STs) was performed by immunohistological staining. α(1,2)-linked fucosylated angiogenic chemokine expression in synovial fluids (SFs) was determined by immunoprecipitation and lectin blotting. To determine the angiogenic role of α(1,2)-linked fucosylated proteins in RA, we performed human dermal microvascular endothelial cell (HMVEC) chemotaxis and Matrigel assays using nondepleted and α(1,2)-linked fucosylated protein depleted RA SFs. To examine the production of proangiogenic chemokines by fucosyltransferase 1 (fut1) in HMVECs, cells were transfected with fut1 sense or antisense oligonucleotides, and enzyme-linked immunosorbent assay was performed. We then studied mouse lung endothelial cell (MLEC) chemotaxis using wild type and fut1 gene deficient MLECs. Results α(1,2)-linked fucosylated proteins on RA ST endothelial cells (ECs) were highly expressed compared to normal ST. α(1,2)-linked fucosylated monocyte chemoattract protein-1 (MCP-1)/CCL2 was present in RA SFs, and was significantly elevated compared to osteoarthritis SFs. Depletion of α(1,2)-linked fucosylated proteins in RA SFs induced less HMVEC migration and tube formation compared to nondepleted RA SFs. We found that blocking fut1 expression in ECs resulted in decreased MCP-1/CCL2 and regulated upon activation and normal T cell expressed and secreted (RANTES)/CCL5 production. Finally, we showed that fut1 regulates EC migration in response to vascular endothelial cell growth factor. Conclusions α(1,2)-linked fucosylation by fut1 may be an important new target for angiogenic diseases like RA. PMID:24692243

  17. Salicylate pharmacokinetics in patients with rheumatoid arthritis.

    PubMed Central

    Owen, S G; Roberts, M S; Friesen, W T; Francis, H W

    1989-01-01

    1. The pharmacokinetics of salicylic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2. The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3. Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4. During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5. Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations. PMID:2590603

  18. Epidemiology of Rheumatoid Arthritis in Southern Albania

    PubMed Central

    Koko, Vjollca; Ndrepepa, Ana; Skenderaj, Skender

    2015-01-01

    Objectives: The aim of this study was to assess the prevalence, incidence and the burden of rheumatoid arthritis (RA) in the Southern Albania. Material and Methods: This is an epidemiologic observational study with cross-sectional analyses of all patients with RA who lived in Southern Albania during the 1995-2011 years. The RA prevalence, incidence and disability-adjusted life years (DALY) were assessed. Results: During the 1995-2011 years, 194 patients (154 females and 40 males) with RA living in Southern Albania were identified. The prevalence of RA in 2011 was 0.25% in general population and 0.34% in adult (>14 years) population. The incidence of RA in 2011 was 0.012% (12 new cases per 100000 inhabitants) and 0.016% (16 new cases per 100000 adults). The prevalence increased (from 0.036% in 1996 to 0.25% in 2011) and the incidence did not change over the study period. The mortality was 3.2% (n=7 deaths). The DALY due to RA was 823 years per 100000 inhabitants during 1995-2011 years. Conclusion: RA in Southern Albania has a prevalence of 0.25 % and an annual incidence of 0.012% in the general population in 2011. RA was responsible for a considerable burden on the health of population during the 1995-2011 years. PMID:26236163

  19. TNF inhibitor therapy for rheumatoid arthritis

    PubMed Central

    MA, XIXI; XU, SHENGQIAN

    2013-01-01

    Immunotherapy has markedly improved treatment outcomes in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α antagonists, such as infliximab (IFX), etanercept (ETN), adalimumab (ADA), golimumab (GOLI) and certolizumab pegol (CZP) have been widely used for the treatment of RA. IFX provides significant, clinically relevant improvement in physical function and the quality of life, inhibits progressive joint damage and sustains improvement in the signs and symptoms of patients with RA. ETN is effective and safe for patients with RA. Combination therapy with ETN plus methotrexate (MTX) reduces disease activity, decreases total joint score progression, slows the pace of joint destruction and improves function more effectively compared to any of the monotherapies. ADA with or without MTX also relieves the signs and symptoms of RA. CZP and GOLI expand the therapeutic schedule for patients with RA. The TNF-α inhibitors have similar efficacy, but distinct clinical pharmacokinetic and -dynamic properties. The common adverse events of these TNF-α antagonists include adverse reactions, infections and injection-site reaction. Additionally, these adverse events are mostly mild or moderate and their incidence is low. Certain patients exhibit a lack of response to anti-TNF-α therapies. Some patients may discontinue the initial drug and switch to a second anti-TNF-α agent. The shortage of clinical response to one agent may not predict deficiency of response to another. This review mainly addresses the latest developments of these biological agents in the treatment of RA. PMID:24648915

  20. Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: Rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives

    PubMed Central

    Sparks, Jeffrey A.; Iversen, Maura D.; Kroouze, Rachel Miller; Mahmoud, Taysir G.; Triedman, Nellie A.; Kalia, Sarah S.; Atkinson, Michael L.; Lu, Bing; Deane, Kevin D.; Costenbader, Karen H.; Green, Robert C.; Karlson, Elizabeth W.

    2014-01-01

    We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention. PMID:25151341

  1. Differential Methylation as a Biomarker of Response to Etanercept in Patients With Rheumatoid Arthritis

    PubMed Central

    Plant, Darren; Webster, Amy; Nair, Nisha; Oliver, James; Smith, Samantha L.; Eyre, Steven; Hyrich, Kimme L.; Wilson, Anthony G.; Morgan, Ann W.; Isaacs, John D.; Worthington, Jane

    2016-01-01

    Objective Biologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide biomarkers predictive of response to tumor necrosis factor inhibitor (TNFi) therapy in patients with RA. Methods An epigenome‐wide association study was performed on pretreatment whole blood DNA from patients with RA. Patients who displayed good response (n = 36) or no response (n = 36) to etanercept therapy at 3 months were selected. Differentially methylated positions were identified using linear regression. Variance of methylation at differentially methylated positions was assessed for correlation with cis‐acting single‐nucleotide polymorphisms (SNPs). A replication experiment for prioritized SNPs was performed in an independent cohort of 1,204 RA patients. Results Five positions that were differentially methylated between responder groups were identified, with a false discovery rate of <5%. The top 2 differentially methylated positions mapped to exon 7 of the LRPAP1 gene on chromosome 4 (cg04857395, P = 1.39 × 10−8 and cg26401028, P = 1.69 × 10−8). The A allele of the SNP rs3468 was correlated with higher levels of methylation for both of the top 2 differentially methylated positions (P = 2.63 × 10−7 and P = 1.05 × 10−6, respectively). Furthermore, the A allele of rs3468 was correlated with European League Against Rheumatism nonresponse in the discovery cohort (P = 0.03; n = 56) and in the independent replication cohort (P = 0.003; n = 1,204). Conclusion We identify DNA methylation as a potential biomarker of response to TNFi therapy, and we report the association between response and the LRPAP1 gene, which encodes a chaperone of low‐density lipoprotein

  2. [Colonic microbial biocenosis in rheumatoid arthritis].

    PubMed

    Gul'neva, M Iu; Noskov, S M

    2011-01-01

    The aim of the work was to study colonic microbial biocenosis and colonizing ability of opportunistic bacteria in 32 patients with rheumatoid arthritis (RA) and 30 healthy subjects. RA was diagnosed based on the American Rheumatism Association criteria (1987). Qualitative and quantitative composition of the microflora was detected by a bacteriological method. StatSoft Statistics 6.0 was used to treat the data obtained. RA was associated with significant modification of the intestinal flora, viz. decrease in lactobacteria and significant increase of enterococci, clostridia, colibacteria showing reduced enzymatic activity, and opportunistic species. Also, symbiotic relationships between microorganisms altered. The fraction of bifidobacteria, bacteroids, and lactopositive colibacteria reduced while the abundance of opportunistic enterobacteria and staphylococci was elevated. Opportunistic Enterobacteriaceae were present in urine and nasal mucosa which suggested their translocation from the intestines. It is concluded that changes in intestinal microflora and colonization by opportunistic bacteria enhance the risk of development of co-morbid conditions in patients with RA. PMID:21932563

  3. [Management of rheumatoid arthritis medications and pregnancy].

    PubMed

    Funakubo Asanuma, Yu

    2015-01-01

    Rheumatoid arthritis (RA) affects mainly women during their childbearing years. As aging of childbirth advances in Japan, women who plan pregnancy would increase after they developed RA. Recent findings showed that high disease activity of RA might impair fertility. Planning pregnancy is preferable after female patients achive and maintain low disease activity or remission of RA. Women on methotrexate, which is the anchor drug for RA, need to discontinue the medication with a high risk of causing birth defects during conception and pregnancy. Data of RA patients exposed TNF inhibitors during pregnancy has been accumulating in recent years. These data suggest that increased risk of spontaneous abortion and congenital abnomalies has not been observed. Although there is insufficient data about safety of breastfeeding while using TNF inhibitors, the secretion of the drugs in breast milk is very little and fetal toxicity has not been observed. Since long term safety of children exposed TNF inhibitors in uterus has not been established, we should discontinue the drugs as soon as pregnancy is recognized. TNF inhibitors may be an useful tools for management of active RA resistant to conventional DMARDs in women who desire to bear children. PMID:25765688

  4. An Appendectomy Increases the Risk of Rheumatoid Arthritis: A Five-Year Follow-Up Study

    PubMed Central

    Kao, Li-Ting; Kao, Senyeong; Lin, Herng-Ching; Lee, Cha-Ze

    2015-01-01

    Many studies have reported a possible association of an appendectomy with rheumatoid arthritis (RA). However, findings of the relationship between an appendectomy and RA remain inconsistent. Furthermore, all such studies were conducted in Western societies, and relevant studies on the relationship between an appendectomy and RA in Asian countries are still lacking. In this study, we investigated the relationship between an appendectomy and the subsequent risk of RA using a population-based dataset. We retrieved data for this retrospective cohort study from the Taiwan “Longitudinal Health Insurance Database 2005”. We included 4,294 subjects who underwent an appendectomy in the study cohort and 12,882 matched subjects in the comparison cohort. We individually tracked each subject for a 5-year period from their index date to identify those who developed RA. A stratified Cox proportional hazard regression was performed to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI) for the subsequent development of RA during the 5-year follow-up period between subjects who underwent an appendectomy and comparison subjects. Of the sampled subjects, 93 (0.54%) received a diagnosis of RA during the 5-year follow-up period: 33 from the study cohort (0.77% of subjects who underwent an appendectomy) and 60 from the comparison cohort (0.47% of comparison subjects) (p<0.001). After censoring individuals who died during the follow-up period and adjusting for subjects’ monthly income and geographic region, the HR of RA during the 5-year follow-up period was 1.61 (95% CI = 1.05~2.48) for subjects who underwent an appendectomy compared to comparison subjects. We found that among females, the adjusted HR of RA was 1.76 (95% CI = 1.04~2.96) for subjects who underwent an appendectomy compared to comparison subjects. However, there was no increased hazard of RA for males who underwent an appendectomy compared to comparison subjects. We concluded that female

  5. Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis

    PubMed Central

    Dejaco, Christian; Klotz, Werner; Larcher, Heike; Duftner, Christina; Schirmer, Michael; Herold, Manfred

    2006-01-01

    Antibodies directed against citrullinated vimentin are members of the family of autoantibodies reactive with citrullinated proteins and are among the most specific serological markers for the diagnosis of rheumatoid arthritis (RA). This study was performed to test the diagnostic value of a newly developed enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with a second-generation anti-cyclic citrullinated peptides (anti-CCP2) ELISA test system. Blinded sera from 631 patients (409 consecutive out-patients and 222 randomly selected stored sera) with RA (n = 164) and non-RA (osteoarthritis [n = 120], polymyalgia rheumatica/giant cell arteritis [n = 80], spondyloarthritis [n = 36], and other inflammatory rheumatic or non-inflammatory disease [n = 67]) were tested for the presence of anti-MCV and anti-CCP2 antibodies according to the manufacturers' instructions. The diagnostic performance of the anti-MCV was comparable with the anti-CCP2 assay for the diagnosis of RA according to the calculated area under the curve (0.824; 95% confidence interval (CI) 0.778–0.870 versus 0.818; 95% CI 0.767–0.869) as analysed by receiving operating characteristic curve. When categorised with a cutoff value of 20.0 U/ml (as recommended by the manufacturer), sensitivity and specificity of the anti-MCV ELISA were 69.5% (95% CI 61.9%–76.5%) and 90.8% (86.9%–93.8%), respectively, compared with 70.1% (62.5%–77.0%) and 98.7% (96.7%–99.6%) of the anti-CCP2 assay. Using the cutoff values of 19.0 U/ml and 81.5 U/ml for the anti-MCV test to obtain a sensitivity and specificity identical to the anti-CCP2 assay, showed a reduced specificity (89.8%; 85.8%–92.9%) and sensitivity (53.7%; 45.7%–61.5%), respectively, of the anti-MCV ELISA compared with the anti-CCP2 test. In conclusion, the serum ELISA testing for anti-MCV antibodies as well as the anti-CCP-2 assay perform comparably well

  6. Consensus statement on the use of rituximab in patients with rheumatoid arthritis

    PubMed Central

    Smolen, J S; Keystone, E C; Emery, P; Breedveld, F C; Betteridge, N; Burmester, G R; Dougados, M; Ferraccioli, G; Jaeger, U; Klareskog, L; Kvien, T K; Martin‐Mola, E; Pavelka, K

    2007-01-01

    A large number of experts experienced in the treatment of rheumatoid arthritis were involved in formulating a consensus statement on the use of B cell‐targeted treatment with rituximab in patients with rheumatoid arthritis. The statement was supported by data from randomised controlled clinical trials and the substantial literature on oncology. The statement underwent three rounds of discussions until its ultimate formulation. It should guide clinicians in the use of this newly approved biological agent in treating patients with rheumatoid arthritis. PMID:17068064

  7. Prevalence of rheumatoid arthritis in low– and middle–income countries: A systematic review and analysis

    PubMed Central

    Rudan, Igor; Sidhu, Simrita; Papana, Angeliki; Meng, Shi–Jiao; Xin–Wei, Yu; Wang, Wei; Campbell–Page, Ruth M.; Demaio, Alessandro Rhyll; Nair, Harish; Sridhar, Devi; Theodoratou, Evropi; Dowman, Ben; Adeloye, Davies; Majeed, Azeem; Car, Josip; Campbell, Harry; Wang, Wei; Chan, Kit Yee

    2015-01-01

    Background Rheumatoid arthritis (RA) is an autoimmune disorder that affects the small joints of the body. It is one of the leading causes of chronic morbidity in high–income countries, but little is known about the burden of this disease in low– and middle–income countries (LMIC). Methods The aim of this study was to estimate the prevalence of RA in six of the World Health Organization's (WHO) regions that harbour LMIC by identifying all relevant studies in those regions. To accomplish this aim various bibliographic databases were searched: PubMed, EMBASE, Global Health, LILACS and the Chinese databases CNKI and WanFang. Studies were selected based on pre–defined inclusion criteria, including a definition of RA based on the 1987 revision of the American College of Rheumatology (ACR) definition. Results Meta–estimates of regional RA prevalence rates for countries of low or middle income were 0.40% (95% CI: 0.23–0.57%) for Southeast Asian, 0.37% (95% CI: 0.23–0.51%) for Eastern Mediterranean, 0.62% (95% CI: 0.47–0.77%) for European, 1.25% (95% CI: 0.64–1.86%) for American and 0.42% (95% CI: 0.30–0.53%) for Western Pacific regions. A formal meta–analysis could not be performed for the sub–Saharan African region due to limited data. Male prevalence of RA in LMIC was 0.16% (95% CI: 0.11–0.20%) while the prevalence in women reached 0.75% (95% CI: 0.60–0.90%). This difference between males and females was statistically significant (P < 0.0001). The prevalence of RA did not differ significantly between urban and rural settings (P = 0.353). These prevalence estimates represent 2.60 (95% CI: 1.85–3.34%) million male sufferers and 12.21 (95% CI: 9.78–14.67%) million female sufferers in LMIC in the year 2000, and 3.16 (95% CI: 2.25–4.05%) million affected males and 14.87 (95% CI: 11.91–17.86%) million affected females in LMIC in the year 2010. Conclusion Given that majority of the world’s population resides in LMIC, the number of

  8. Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial

    PubMed Central

    Burmester, Gerd R; Rigby, William F; van Vollenhoven, Ronald F; Rubbert-Roth, Andrea; Kelman, Ariella; Dimonaco, Sophie; Mitchell, Nina

    2016-01-01

    Objectives The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA). Methods In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28–erythrocyte sedimentation rate (ESR) <2.6) at week 24. Radiographic and physical function outcomes were also evaluated. We report results through week 52. Results The intent-to-treat population included 1157 patients. Significantly more patients receiving 8 mg/kg TCZ+MTX and 8 mg/kg TCZ+placebo than receiving placebo+MTX achieved DAS28-ESR remission at week 24 (45% and 39% vs 15%; p<0.0001). The 8 mg/kg TCZ+MTX group also achieved significantly greater improvement in radiographic disease progression and physical function at week 52 than did patients treated with placebo+MTX (mean change from baseline in van der Heijde–modified total Sharp score, 0.08 vs 1.14 (p=0.0001); mean reduction in Health Assessment Disability Index, −0.81 vs −0.64 (p=0.0024)). In addition, the 8 mg/kg TCZ+placebo and 4 mg/kg TCZ+MTX groups demonstrated clinical efficacy that was at least as effective as MTX for these key secondary endpoints. Serious adverse events were similar among treatment groups. Adverse events resulting in premature withdrawal occurred in 20% of patients in the 8 mg/kg TCZ+MTX group. Conclusions TCZ is effective in combination with MTX and as monotherapy for the treatment of patients with early RA. Trial registration number ClinicalTrials.gov, number NCT01007435 PMID:26511996

  9. Inherited and noninherited risk factors in rheumatoid arthritis.

    PubMed

    Weyand, C M; Goronzy, J J

    1995-05-01

    Rheumatoid arthritis (RA) is likely the result of a concerted action of several inherited and noninherited factors. Although there is a high suspicion that environmental factors are important, proof is missing. Most information has been collected on genetic risk factors. The inheritance pattern for RA is complex, and there is good evidence that HLA as well as non-HLA genes are involved. Almost all racial-ethnic groups share the association of RA with the HLA-DRB1-encoded sequence motif QKRAA or QRRAA. However, the completeness of the association varies significantly in different ethnic cohorts, as can be expected in a multigene model. The sequence motif translates into a pocket in the antigen-binding site of the HLA-DR molecule. The "rheumatoid pocket" accommodates peptide side chains and has distinct binding characteristics. Epidemiologic evidence points toward a role for non-HLA genes. Candidate genes, such as transporter in antigen processing (TAP) genes are currently explored. Major advances in defining and understanding the contribution of inherited and noninherited factors in RA may come from abandoning the concept of RA as a single entity and accepting a heterogeneity model for RA. Distributions of HLA-DR genes indicate that several subsets of RA patients exist. Seronegative (prognostically good) and seropositive (prognostically worse) patients can be distinguished by the arginine versus lysine substitution at position 71 of the HLA-DRB1 gene. A different dimension of disease, rheumatoid organ disease, appears to be reached in patients with two HLA-DRB1*0401 alleles. Identification of distinct RA subsets may allow us to stratify patients into categories that differ with respect to etiology, disease course, clinical pattern, and treatment response. PMID:7612412

  10. Prostaglandin D2 metabolites as a biomarker of in vivo mast cell activation in systemic mastocytosis and rheumatoid arthritis.

    PubMed

    Cho, Catherine; Nguyen, Anna; Bryant, Katherine J; O'Neill, Sean G; McNeil, H Patrick

    2016-03-01

    Mast cells (MCs) participate in diseases such as systemic mastocytosis (SM) and allergic conditions. Less well understood is the role of MCs in non-allergic inflammatory disorders like rheumatoid arthritis (RA). Studying definitive roles for MCs in human diseases has been hampered by the lack of a well-accepted biomarker for monitoring in vivo MC activation. This study aimed to investigate the utility of urinary tetranor PGDM (T-PGDM) as a biomarker of in vivo MC activation in patients with SM, and apply this biomarker to assess MC involvement in relation to RA disease activity. A prospective, cross-sectional cohort study was conducted to measure a major urinary metabolite of prostaglandin D2, T-PGDM. Urine samples were collected from patients with RA (n = 60), SM (n = 17) and healthy normal controls (n = 16) and T-PGDM excretion was determined by enzyme immunoassay as nanograms per milligram of urinary creatinine (ng/mg Cr). Mean urinary T-PGDM excretion was significantly higher (p < 0.01) in patients with SM compared to controls (37.2 vs. 11.5 ng/mg Cr) with 65% of SM patients showing elevated levels. One third of patients with RA had elevated T-PGDM excretion, and the mean level in the RA group (20.0 ng/mg Cr) was significantly higher than controls (p < 0.01). Medications inhibiting cyclooxygenase reduced T-PGDM excretion. Urinary T-PGDM excretion appears promising as a biomarker of in vivo MC activity and elevated levels in 33% of patients with RA provides evidence of MC activation in this disease. PMID:27042302

  11. Differences in the prevalence and characteristics of metabolic syndrome in rheumatoid arthritis and osteoarthritis: a multicentric study.

    PubMed

    Šalamon, Lea; Morović-Vergles, Jadranka; Marasović-Krstulović, Daniela; Kehler, Tatjana; Šakić, Davorin; Badovinac, Olga; Vlak, Tonko; Novak, Srđan; Štiglić-Rogoznica, Nives; Hanih, Marino; Bedeković, Dražen; Grazio, Simeon; Kadojić, Mira; Milas-Ahić, Jasminka; Prus, Višnja; Stamenković, Doris; Šošo, Daniela; Anić, Branimir; Babić-Naglić, Ðurđica; Gamulin, Stjepan

    2015-12-01

    The purpose of the study was to examine whether rheumatoid arthritis (RA) patients have higher prevalence of metabolic syndrome (MetS) than osteoarthritis (OA) patients in association with a higher level of chronic systemic inflammation in rheumatoid arthritis. A total of 583 RA and 344 OA outpatients were analyzed in this multicentric study. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. A 1.6-fold higher prevalence of MetS was found in patients with OA compared with the RA patients. Among the parameters of MetS, patients with OA had significantly higher levels of waist circumference, systolic blood pressure, fasting blood glucose and triglycerides, whereas HDL cholesterol and diastolic blood pressure values were similar in both groups of patients. Higher values of inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] in MetS than in non-MetS patients and higher prevalence of MetS in patients with CRP level ≥5 mg/L in both RA and OA patients were found. In multivariate logistic regression analysis, significant predictors of MetS were type of arthritis (OA vs. RA; OR 2.5 [95 % CI 1.82-3.43]), age (OR 1.04 [95 % CI 1.03-1.06]) and ESR (OR 1.01; [95 % CI 1.00-1.01]). The significant association between OA and MetS was maintained in the regression model that controlled for body mass index (OR 1.87 [95 % CI 1.34-2.61]). The present analysis suggests that OA is associated with an increased risk of MetS, which may be due to a common underlying pathogenic mechanism. PMID:26059944

  12. Rheumatoid Arthritis When Your Immune System Attacks Your Body | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Understanding Rheumatoid Arthritis (RA) Rheumatoid Arthritis When Your Immune System Attacks Your Body Past Issues / Summer 2014 Table ... disease, which means the arthritis results from your immune system attacking your body's own tissues. The course of ...

  13. Rheumatoid Arthritis When Your Immune System Attacks Your Body | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Rheumatoid Arthritis (RA) Rheumatoid Arthritis When Your Immune System Attacks Your Body Past Issues / Summer 2014 Table ... which means the arthritis results from your immune system attacking your body's own tissues. The course of ...

  14. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss

    PubMed Central

    Krishnamurthy, Akilan; Joshua, Vijay; Haj Hensvold, Aase; Jin, Tao; Sun, Meng; Vivar, Nancy; Ytterberg, A Jimmy; Engström, Marianne; Fernandes-Cerqueira, Cátia; Amara, Khaled; Magnusson, Malin; Wigerblad, Gustaf; Kato, Jungo; Jiménez-Andrade, Juan Miguel; Tyson, Kerry; Rapecki, Stephen; Lundberg, Karin; Catrina, Sergiu-Bogdan; Jakobsson, Per-Johan; Svensson, Camilla; Malmström, Vivianne; Klareskog, Lars; Wähämaa, Heidi; Catrina, Anca I

    2016-01-01

    Objectives Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) appear before disease onset and are associated with bone destruction. We aimed to dissect the role of ACPAs in osteoclast (OC) activation and to identify key cellular mediators in this process. Methods Polyclonal ACPA were isolated from the synovial fluid (SF) and peripheral blood of patients with RA. Monoclonal ACPAs were isolated from single SF B-cells of patients with RA. OCs were developed from blood cell precursors with or without ACPAs. We analysed expression of citrullinated targets and peptidylarginine deiminases (PAD) enzymes by immunohistochemistry and cell supernatants by cytometric bead array. The effect of an anti-interleukin (IL)-8 neutralising antibody and a pan-PAD inhibitor was tested in the OC cultures. Monoclonal ACPAs were injected into mice and bone structure was analysed by micro-CT before and after CXCR1/2 blocking with reparixin. Results Protein citrullination by PADs is essential for OC differentiation. Polyclonal ACPAs enhance OC differentiation through a PAD-dependent IL-8-mediated autocrine loop that is completely abolished by IL-8 neutralisation. Some, but not all, human monoclonal ACPAs derived from single SF B-cells of patients with RA and exhibiting distinct epitope specificities promote OC differentiation in cell cultures. Transfer of the monoclonal ACPAs into mice induced bone loss that was completely reversed by the IL-8 antagonist reparixin. Conclusions We provide novel insights into the key role of citrullination and PAD enzymes during OC differentiation and ACPA-induced OC activation. Our findings suggest that IL8-dependent OC activation may constitute an early event in the initiation of the joint specific inflammation in ACPA-positive RA. PMID:26612338

  15. Treatment of intractable rheumatoid arthritis with lymphoid irradiation

    SciTech Connect

    Strober, S.; Kotzin, B.L.; Hoppe, R.T.; Slavin, S.; Gottlieb, M.; Calin, A.; Fuks, Z.; Kaplan, H.S.

    1981-01-01

    Subdiaphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdiaphragmatic lymphoid tissues in fractionated doses of 150 to 250 rad each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.

  16. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis.

    PubMed

    Stahl, Eli A; Wegmann, Daniel; Trynka, Gosia; Gutierrez-Achury, Javier; Do, Ron; Voight, Benjamin F; Kraft, Peter; Chen, Robert; Kallberg, Henrik J; Kurreeman, Fina A S; Kathiresan, Sekar; Wijmenga, Cisca; Gregersen, Peter K; Alfredsson, Lars; Siminovitch, Katherine A; Worthington, Jane; de Bakker, Paul I W; Raychaudhuri, Soumya; Plenge, Robert M

    2012-05-01

    The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases. PMID:22446960

  17. Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications.

    PubMed Central

    Colville-Nash, P R; Scott, D L

    1992-01-01

    Rheumatoid arthritis can be considered as one of the family of 'angiogenesis dependent diseases'. Angiogenesis in rheumatoid arthritis is controlled by a variety of factors found in the synovial fluid and pannus tissue. Modulation of the angiogenic component of the disease may alter the pathogenesis of the condition, and subsequent cartilage and joint destruction, by reducing the area of the endothelium in the pannus and restricting pannus growth. Current therapeutic strategies exert, to varying extents, an inhibitory effect on the angiogenic process. In particular, the mode of action of the slow acting antirheumatic drugs may be due to their effect on the angiogenic response. The development of novel angiostatic treatments for chronic inflammatory joint disease may lead to a new therapeutic approach in controlling disease progression. PMID:1378718

  18. Indium-111 leukocyte imaging in patients with rheumatoid arthritis

    SciTech Connect

    Uno, K.; Matsui, N.; Nohira, K.; Suguro, T.; Kitakata, Y.; Uchiyama, G.; Miyoshi, T.; Uematsu, S.; Inoue, S.; Arimizu, N.

    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 determined 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.

  19. Ascites and other incidental findings revealing undiagnosed systemic rheumatoid arthritis.

    PubMed

    Szeto, Matthew Chak Hin; Disney, Benjamin; Perkins, Philip; Wood, Gordon

    2015-01-01

    We describe a case of a 43-year-old man presenting to the gastroenterology outpatient department with exudative ascites. Mediastinal lymphadenopathy, pericardial effusion and pleural effusion were detected on further imaging. Further clinical examination revealed subcutaneous nodules on the left arm, which were confirmed to be rheumatoid nodules on histology. Inflammatory markers were elevated with positive serology for rheumatoid factor and anticyclic citrullinated protein antibody. Our investigations excluded tuberculosis, pancreatitis and malignancy in the patient. Following review by a rheumatologist, a diagnosis of systemic rheumatoid arthritis (RA) was made. Pleuritis and pericarditis are well recognised as extra-articular manifestation of RA. Ascites, however, is rarely recognised as a manifestation of RA. Our literature search revealed two other cases of ascites due to RA disease activity, and both patients had long-standing known RA. This case adds to the discussion on whether ascites and peritonitis should be classified as extra-articular manifestations of RA. PMID:26055583

  20. New laboratory markers for the management of rheumatoid arthritis patients.

    PubMed

    Foti, Daniela P; Greco, Marta; Palella, Eleonora; Gulletta, Elio

    2014-12-01

    Rheumatoid arthritis, the most prominent of systemic autoimmune rheumatic diseases, represents an important social health problem. Recent insights into the immunopathogenic mechanism of this complex and multiform illness might open new perspectives for a more appropriate laboratory approach. In this review we focus on the most relevant pathogenetic mechanism; indicating the laboratory biomarkers specifically linked to early diagnosis, prognosis, evolutive aspects of the disease, and therapeutic efficacy. Evidence based on laboratory medicine could provide the best outcome for patients. PMID:24933628

  1. Food intolerance in rheumatoid arthritis. I. A double blind, controlled trial of the clinical effects of elimination of milk allergens and azo dyes.

    PubMed Central

    van de Laar, M A; van der Korst, J K

    1992-01-01

    The hypothetically negative influence of food on the clinical activity of seropositive rheumatoid arthritis was studied using two types of artificial elementary food. One diet was allergen free, the other allergen restricted, containing only lactoproteins and yellow dyes. Ninety four patients entered the study, which lasted 12 weeks. During the second four week period they were randomly assigned to one of the two artificial foods. Comparison between baseline and subsequent periods showed only subjective improvements. No differences were seen between the clinical effects of the two tested diets. Nine patients (three in the allergen restricted group, six in the allergen free group) showed favourable responses, followed by marked disease exacerbation during rechallenge. Dietary manipulation also brought about changes in objective disease activity parameters in these patients. The existence of a subgroup of patients in whom food intolerance influences the activity of rheumatoid factor seropositive rheumatoid arthritis deserves serious consideration. PMID:1575571

  2. Macrophage heterogeneity in the context of rheumatoid arthritis.

    PubMed

    Udalova, Irina A; Mantovani, Alberto; Feldmann, Marc

    2016-08-01

    Macrophages are very important in the pathogenesis of rheumatoid arthritis (RA). The increase in the number of sublining macrophages in the synovium is an early hallmark of active rheumatic disease, and high numbers of macrophages are a prominent feature of inflammatory lesions. The degree of synovial macrophage infiltration correlates with the degree of joint erosion, and depletion of these macrophages from inflamed tissue has a profound therapeutic benefit. Research has now uncovered an unexpectedly high level of heterogeneity in macrophage origin and function, and has emphasized the role of environmental factors in their functional specialization. Although the heterogeneous populations of macrophages in RA have not been fully characterized, preliminary results in mouse models of arthritis have contributed to our understanding of the phenotype and ontogeny of synovial macrophages, and to deciphering the properties of monocyte-derived infiltrating and tissue-resident macrophages. Elucidating the molecular mechanisms that drive polarization of macrophages towards proinflammatory or anti-inflammatory phenotypes could lead to identification of signalling pathways that inform future therapeutic strategies. PMID:27383913

  3. The interplay between inflammation and metabolism in rheumatoid arthritis.

    PubMed

    Chimenti, M S; Triggianese, P; Conigliaro, P; Candi, E; Melino, G; Perricone, R

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone that lead to joint destruction. The autoimmune process in RA depends on the activation of immune cells, which use intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. An intricate cytokine network participates in inflammation and in perpetuation of disease by positive feedback loops promoting systemic disorder. The widespread systemic effects mediated by pro-inflammatory cytokines in RA impact on metabolism and in particular in lymphocyte metabolism. Moreover, RA pathobiology seems to share some common pathways with atherosclerosis, including endothelial dysfunction that is related to underlying chronic inflammation. The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine-mediated inflammatory processes in RA. Altered metabolic fingerprints may be useful in predicting the development of RA in patients with early arthritis as well as in the evaluation of the treatment response. Evidence supports the role of metabolomic analysis as a novel and nontargeted approach for identifying potential biomarkers and for improving the clinical and therapeutical management of patients with chronic inflammatory diseases. Here, we review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response. PMID:26379192

  4. The interplay between inflammation and metabolism in rheumatoid arthritis

    PubMed Central

    Chimenti, M S; Triggianese, P; Conigliaro, P; Candi, E; Melino, G; Perricone, R

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone that lead to joint destruction. The autoimmune process in RA depends on the activation of immune cells, which use intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. An intricate cytokine network participates in inflammation and in perpetuation of disease by positive feedback loops promoting systemic disorder. The widespread systemic effects mediated by pro-inflammatory cytokines in RA impact on metabolism and in particular in lymphocyte metabolism. Moreover, RA pathobiology seems to share some common pathways with atherosclerosis, including endothelial dysfunction that is related to underlying chronic inflammation. The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine-mediated inflammatory processes in RA. Altered metabolic fingerprints may be useful in predicting the development of RA in patients with early arthritis as well as in the evaluation of the treatment response. Evidence supports the role of metabolomic analysis as a novel and nontargeted approach for identifying potential biomarkers and for improving the clinical and therapeutical management of patients with chronic inflammatory diseases. Here, we review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response. PMID:26379192

  5. [Recent advances in upper extremity surgery for rheumatoid arthritis].

    PubMed

    Nishida, Keiichiro

    2016-06-01

    The number of cases with rheumatoid arthritis who requires arthroscopic synovectomy is declining, but it is still a useful procedure in combination with effective pharmacologic disease control. For the destruction of glenohumeral joint, total shoulder arthroplasty is effective for pain relief and functional outcome for patients without rotator cuff impairment. The reverse shoulder arthroplasty has been shown favorable short-term results, but need a careful indication for rheumatoid shoulder with poor bone stock and bone quality. Linked or unlinked total elbow arthroplasty are now reliable methods for the reconstruction of rheumatoid elbows with acceptable long-term survival. Joint replacement surgery for proximal interphalangeal joint is a challenging procedure in terms of relatively high complication rate and disappointing improvement in range of motion, whereas achieves good patients' satisfaction for pain relief and improved finger appearances. PMID:27311189

  6. Managing early presentation of rheumatoid arthritis. Systematic overview.

    PubMed Central

    Glazier, R.

    1996-01-01

    OBJECTIVE: To describe evidence-based management of patients presenting to family physicians with typical signs and symptoms of recent onset of rheumatoid arthritis (RA). STUDY SELECTION: Articles for critical review were included if relevant to primary care management of early RA (less than 1 year duration). Sources included MEDLINE from 1966 to December 1995, the reference library of the Arthritis Community Research and Evaluation Unit, and conference abstracts. FINDINGS: Evidence from randomized, controlled trials supports the short-term benefit of nonsteroidal anti-inflammatory drugs, disease-modifying agents for rheumatic diseases, intravenous pulse corticosteroid therapy, intra-articular therapy, aerobic exercise, patient education, psychologic intervention, home physiotherapy, home occupational therapy, and rehabilitation programs. Some evidence favours acetaminophen for analgesia, low-dose oral corticosteroids for symptom control, and referral to a rheumatologist. Evidence for rest, ice, and heat for symptom control is conflicting and based on low-quality studies. CONCLUSION: Family physicians play an important role in establishing early and accurate diagnosis of RA, coordinating therapy, and providing ongoing support, education, and monitoring to patients and their families. PMID:8688694

  7. Efficient and Non-Toxic Biological Response Carrier Delivering TNF-α shRNA for Gene Silencing in a Murine Model of Rheumatoid Arthritis.

    PubMed

    Song, Jialin; Chen, Yinghui; Jiang, Shichao; Yang, Kejia; Li, Xiaoming; Zhao, Xiaotian; Ouyang, Yuanming; Fan, Cunyi; Yuan, Weien

    2016-01-01

    Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA). In this study, we pre-synthetized a degradable cationic polymer (PDAPEI) from 2,6-pyridinedicarboxaldehyde and low-molecular-weight polyethyleneimine (PEI, Mw = 1.8 kDa) as a gene vector for the delivery of TNF-α shRNA. The PDAPEI/pDNA complex showed a suitable particle size and stable zeta potential for transfection. In vitro study of the PDAPEI/pDNA complex revealed a lower cytotoxicity and higher transfection efficiency when transfecting TNF-α shRNA to macrophages by significantly down-regulating the expression of TNF-α. Moreover, the complex was extremely efficient in decreasing the severity of arthritis in mice with collagen-induced arthritis. PDAPEI delivered TNF-α shRNA has great potential in the treatment of RA. PMID:27594856

  8. Efficient and Non-Toxic Biological Response Carrier Delivering TNF-α shRNA for Gene Silencing in a Murine Model of Rheumatoid Arthritis

    PubMed Central

    Song, Jialin; Chen, Yinghui; Jiang, Shichao; Yang, Kejia; Li, Xiaoming; Zhao, Xiaotian; Ouyang, Yuanming; Fan, Cunyi; Yuan, Weien

    2016-01-01

    Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA). In this study, we pre-synthetized a degradable cationic polymer (PDAPEI) from 2,6-pyridinedicarboxaldehyde and low-molecular-weight polyethyleneimine (PEI, Mw = 1.8 kDa) as a gene vector for the delivery of TNF-α shRNA. The PDAPEI/pDNA complex showed a suitable particle size and stable zeta potential for transfection. In vitro study of the PDAPEI/pDNA complex revealed a lower cytotoxicity and higher transfection efficiency when transfecting TNF-α shRNA to macrophages by significantly down-regulating the expression of TNF-α. Moreover, the complex was extremely efficient in decreasing the severity of arthritis in mice with collagen-induced arthritis. PDAPEI delivered TNF-α shRNA has great potential in the treatment of RA. PMID:27594856

  9. Dispositional Affect in Unique Subgroups of Patients with Rheumatoid Arthritis

    PubMed Central

    Rice, Danielle B.; Mehta, Swati; Pope, Janet E.; Harth, Manfred; Shapiro, Allan; Teasell, Robert W.

    2016-01-01

    Background. Patients with rheumatoid arthritis may experience increased negative outcomes if they exhibit specific patterns of dispositional affect. Objective. To identify subgroups of patients with rheumatoid arthritis based on dispositional affect. The secondary objective was to compare mood, pain catastrophizing, fear of pain, disability, and quality of life between subgroups. Methods. Outpatients from a rheumatology clinic were categorized into subgroups by a cluster analysis based on dispositional affect. Differences in outcomes were compared between clusters through multivariate analysis of covariance. Results. 227 patients were divided into two subgroups. Cluster 1 (n = 85) included patients reporting significantly higher scores on all dispositional variables (experiential avoidance, anxiety sensitivity, worry, fear of pain, and perfectionism; all p < 0.001) compared to patients in Cluster 2 (n = 142). Patients in Cluster 1 also reported significantly greater mood impairment, pain anxiety sensitivity, and pain catastrophizing (all p < 0.001). Clusters did not differ on quality of life or disability. Conclusions. The present study identifies a subgroup of rheumatoid arthritis patients who score significantly higher on dispositional affect and report increased mood impairment, pain anxiety sensitivity, and pain catastrophizing. Considering dispositional affect within subgroups of patients with RA may help health professionals tailor interventions for the specific stressors that these patients experience. PMID:27445594

  10. Long-term results of cementless primary total hip arthroplasty with a threaded cup and a tapered, rectangular titanium stem in rheumatoid arthritis and osteoarthritis.

    PubMed

    Zwartele, Rob; Peters, Anil; Brouwers, Johannes; Olsthoorn, Paul; Brand, Ronald; Doets, Cornelis

    2008-10-01

    The aim of this study was to assess the outcome of primary cementless total hip arthroplasty in rheumatoid arthritis patients and to compare the results with osteoarthritis patients. Sixty-four patients (77 hips) with rheumatoid arthritis and 120 patients (135 hips) with osteoarthritis had a conical-shaped Zweymueller threaded cup and a tapered, rectangular Zweymueller stem implanted and were assessed after an average of 12.5 years. The endpoints for survival analysis were failure of one or both components due to radiographic loosening or revision. Revision was defined as exchange of cup, stem or both. When the PE-insert or the ceramic ball head were exchanged leaving cup and stem in place, e.g. for PE-wear or dislocation, this was not considered a revision but a re-intervention. No differences were found in survival rates; however, in the rheumatoid arthritis group there was an increased rate of malposition of the cup, avulsions of the greater trochanter, and increased bone resorption in the trochanteric region. This study shows that despite altered biomechanical properties of rheumatoid bone, mechanical stability and osseous integration of cementless prosthesis are not compromised and, although a higher complication rate did occur, long-term survival is excellent. PMID:17609955

  11. 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

  12. Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Pathogenic Role or Just an Epiphenomenon?

    PubMed

    Dantas, Andréa Tavares; Marques, Claudia Diniz Lopes; da Rocha Junior, Laurindo Ferreira; Cavalcanti, Mariana Brayner; Gonçalves, Sayonara Maria Calado; Cardoso, Pablo Ramon Gualberto; Mariz, Henrique de Ataide; Rego, Moacyr Jesus Barreto de Melo; Duarte, Angela Luzia Branco Pinto; Pitta, Ivan da Rocha; Pitta, Maira Galdino da Rocha

    2015-01-01

    The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618 pg/mL) and in SLE patients (12,26 ± 25,235 pg/mL) than in healthy individuals (1,22 ± 0,706 pg/mL) (p < 0,001). In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels (r = -0,1948; p = 0,0378). In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target. PMID:26078482

  13. Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Pathogenic Role or Just an Epiphenomenon?

    PubMed Central

    Dantas, Andréa Tavares; Marques, Claudia Diniz Lopes; da Rocha Junior, Laurindo Ferreira; Cavalcanti, Mariana Brayner; Gonçalves, Sayonara Maria Calado; Cardoso, Pablo Ramon Gualberto; Mariz, Henrique de Ataide; Rego, Moacyr Jesus Barreto de Melo; Duarte, Angela Luzia Branco Pinto; Pitta, Ivan da Rocha; Pitta, Maira Galdino da Rocha

    2015-01-01

    The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618 pg/mL) and in SLE patients (12,26 ± 25,235 pg/mL) than in healthy individuals (1,22 ± 0,706 pg/mL) (p < 0,001). In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels (r = −0,1948;  p = 0,0378). In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target. PMID:26078482

  14. Activation of NALP1 inflammasomes in rats with adjuvant arthritis; a novel therapeutic target of carboxyamidotriazole in a model of rheumatoid arthritis

    PubMed Central

    Zhu, Lei; Li, Juan; Guo, Lei; Yu, Xiaoli; Wu, Danwei; Luo, Lifeng; Zhu, Lingzhi; Chen, Wei; Chen, Chen; Ye, Caiying; Zhang, Dechang

    2015-01-01

    Background and Purpose Pro-inflammatory cytokines are important in rheumatoid arthritis (RA) and their production is mainly regulated by NF-κB and inflammasomes. Carboxyamidotriazole (CAI) exhibits potent anti-inflammatory activities by decreasing cytokines. Here, we have investigated NACHT, LRR and PYD domains-containing protein (NALP) inflammasomes in a rat model of RA and explored the therapeutic effects of CAI in this model and the involvement of NF-κB and inflammasomes in the actions of CAI. Experimental Approach The anti-arthritic effects of CAI were assessed in the adjuvant arthritis (AA) model in rats, using radiological and histological techniques. NALP1 and NALP3 inflammasomes, NF-κB pathway and pro-inflammatory cytokines levels were measured with Western blots, immunohistochemistry and elisa. Key Results CAI decreased the arthritis index, improved radiological and histological changes, and reduced synovial IL-1β, IL-6, IL-18 and TNF-α levels in rats with AA. Compared with normal rats, the 70 kDa NALP1 isoform was up-regulated, NALP3 was down-regulated, and levels of the 165 kDa NALP1 isoform and the adaptor protein ASC were unchanged in synovial tissue from AA rats. CAI reduced the 70 kDa NALP1 isoform and restored NALP3 levels in AA rats; CAI inhibited caspase-1 activation in AA synovial tissue, but not its enzymic activity in vitro. In addition, CAI reduced expression of p65 NF-κB subunit and IκBα phosphorylation and degradation in AA rats. Conclusion and Implications NALP1 inflammasomes were activated in synovial tissues from AA rats and appeared to be a novel therapeutic target for RA. CAI could have therapeutic value in RA by inhibiting activation of NF-κB and NALP1 inflammasomes and by decreasing pro-inflammatory cytokines. PMID:25799914

  15. Magnet therapy for the relief of pain and inflammation in rheumatoid arthritis (CAMBRA): A randomised placebo-controlled crossover trial

    PubMed Central

    Richmond, Stewart J

    2008-01-01

    Background Rheumatoid arthritis is a common inflammatory autoimmune disease. Although disease activity may be managed effectively with prescription drugs, unproven treatments such as magnet therapy are sometimes used as an adjunct for pain control. Therapeutic devices incorporating permanent magnets are widely available and easy to use. Magnets may also be perceived as a more natural and less harmful alternative to analgesic compounds. Of interest to health service researchers is the possibility that magnet therapy might help to reduce the economic burden of managing chronic musculoskeletal disorders. Magnets are extremely cheap to manufacture and prolonged treatment involves a single cost. Despite this, good quality scientific evidence concerning the safety, effectiveness and cost-effectiveness of magnet therapy is scarce. The primary aim of the CAMBRA trial is to investigate the effectiveness of magnet therapy for relieving pain and inflammation in rheumatoid arthritis. Methods/Design The CAMBRA trial employs a randomised double-blind placebo-controlled crossover design. Participant will each wear four devices: a commercially available magnetic wrist strap; an attenuated wrist strap; a demagnetised wrist strap; and a copper bracelet. Device will be allocated in a randomised sequence and each worn for five weeks. The four treatment phases will be separated by wash out periods lasting one week. Both participants and researchers will be blind, as far as feasible, to the allocation of experimental and control devices. In total 69 participants will be recruited from general practices within the UK. Eligible patients will have a verified diagnosis of rheumatoid arthritis that is being managed using drugs, and will be experiencing chronic pain. Outcomes measured will include pain, inflammation, disease activity, physical function, medication use, affect, and health related costs. Data will be collected using questionnaires, diaries, manual pill counts and blood tests

  16. Reactive oxygen and nitrogen species in patients with rheumatoid arthritis as potential biomarkers for disease activity and the role of antioxidants.

    PubMed

    Khojah, Hani M; Ahmed, Sameh; Abdel-Rahman, Mahran S; Hamza, Al-Badr

    2016-08-01

    Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have distinct contribution to the destructive, proliferative synovitis of rheumatoid arthritis (RA) and play a prominent role in cell-signaling events. However, few studies had clarified the role of individual ROS and RNS in the etiopathogenesis of RA. To date, most of the studies were concerned with the measurement of the total oxidative and nitrative stress levels in RA. The aim of this study was to monitor the levels of individual ROS and RNS to emphasize the role that each plays in the pathogenesis of RA and their usefulness as possible biomarkers for the disease activity. In addition, the effect of an antioxidant (ascorbic acid), added to the treatment regimen, on the levels of ROS, RNS and disease activity has been evaluated. Forty-two Saudi RA patients and 40 healthy controls of both genders were included in this study. Serum levels of six different ROS and three different RNS were measured using specific fluorescent probes. The ROS included the hydroxyl radical ((•)OH), the superoxide anion (O2(•-)), hydrogen peroxide (H2O2), the singlet oxygen ((1)O2), the hypochlorite radical (OHCl(•)), and the peroxyl radical (ROO(•)). The RNS included nitric oxide (NO(•)), nitrogen dioxide (ONO-) and peroxynitrite (ONOO-). The main clinical and biochemical markers for disease activity were assessed and correlated with ROS and RNS levels. The clinical markers included the 28 swollen joint count (SJC-28), the 28-tender joint count (TJC-28), morning stiffness and symmetric arthritis, in addition to the disease activity score assessing 28 joints with erythrocyte sedimentation rate (DAS28-ESR). The biochemical markers included undercarboxylated osteocalcin (ucOC), matrix metalloproteinase (MMP-3), ESR, C-reactive protein (CRP), rheumatoid factor (RF) and anticyclic citrullinated polypeptide (Anti-CCP). Ascorbic acid (1mg/day) was added as an antioxidant to the regular treatment regimen of RA patients

  17. A Transmembrane Polymorphism of Fcγ Receptor IIb Is Associated with Kidney Deficiency Syndrome in Rheumatoid Arthritis

    PubMed Central

    Mo, Na; Lai, Ruogu; Luo, Shizi; Xie, Jianglin; Wang, Xizi; Liu, Lijuan; Liu, Xiaoling

    2016-01-01

    Objective. The purpose is to investigate the role of kidney deficiency and the association between kidney deficiency and a polymorphism FcγRIIb 695T>C coding for nonsynonymous substitution IIe232Thr (I232T) in rheumatoid arthritis (RA). Methods. Clinical parameters and autoantibodies were analyzed and genotyping was performed in 159 kidney deficiency and 161 non-kidney-deficiency RA patients. Results. The age of disease onset and disease duration exhibited significant differences between two groups (P < 0.01). Patients with kidney deficiency tend to have higher activity of disease (P < 0.05). Anti-cyclic citrullinated peptides antibodies (ACPA) levels of patients with kidney deficiency were higher than the controls (P = 0.039). 125 (78.6%) kidney deficiency and 114 (70.8%) non-kidney-deficiency patients had both ACPA-positive and RF-positive (P = 0.04, OR = 3.29). FcγRIIb I232TT homozygotes were identified in 10 of 159 (6.3%) kidney deficiency subjects and 1 of 161 (0.6%) controls (P = 0.000, OR = 16.45). Furthermore, in pooled genotype analysis, I232IT and I232TT homozygotes were significantly enriched in kidney deficiency individuals compared with the controls (P = 0.000, OR = 3.79). Frequency of T allele was associated with kidney deficiency RA population (P = 0.000, OR = 3.18). Conclusion. This study confirmed that kidney deficiency was closely associated with disease activity and autoimmune disorder in RA. Kidney deficiency in RA is first to reveal a strong genetic link to FcγRIIb variants. PMID:27051449

  18. Interstitial Lung Disease of the UIP Variant as the Only Presenting Symptom of Rheumatoid Arthritis.

    PubMed

    Agrawal, Abhinav; Thyagarajan, Braghadheeswar; Ceniza, Sidney; Hasan Yusuf, Syed

    2015-01-01

    Rheumatoid arthritis is a chronic inflammatory disease primarily manifesting with symptoms of joint pain. It also involves multiple organ systems in the body, including the lungs. Interstitial lung disease (ILD) is the most common form of pulmonary involvement in rheumatoid arthritis (RA). Without the typical symptoms such as chronic joint pain, establishing the diagnosis of RA could be quite challenging and a high index of suspicion is thereby required to diagnose ILD in patients with RA, thereby delaying treatment and increasing morbidity and mortality. We report a case of a 67-year-old Hispanic male with no previous history of rheumatoid arthritis or symptoms of typical joint pain who comes to the hospital only with the chief complaints of progressive worsening of shortness of breath for a duration of 6 months and was eventually diagnosed with ILD of the usual interstitial pneumonia variant with serologies positive for rheumatoid arthritis. PMID:26137341

  19. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

  20. Pharmacology Update on Chronic Obstructive Pulmonary Disease, Rheumatoid Arthritis, and Major Depression.

    PubMed

    Weatherspoon, Deborah; Weatherspoon, Christopher A; Abbott, Brianna

    2015-12-01

    This article presents a brief review and summarizes current therapies for the treatment of chronic obstructive pulmonary disease, major depression, and rheumatoid arthritis. One new pharmaceutical agent is highlighted for each of the topics. PMID:26596663

  1. Rheumatoid arthritis patients' experience of climate care.

    PubMed

    Vaks, Katrin; Sjöström, Rita

    2015-12-01

    The purpose of this qualitative study was to understand and examine how patients with rheumatoid arthritis (RA) experience climate care and its effects. A qualitative approach was chosen for the study. Two men and six women were interviewed according to a semistructured interview guide. The text was analyzed using a manifest content analysis. The analysis resulted in four categories and 10 subcategories. The interviewees experienced climate care positively. The training was perceived increasing gradually. The patients felt that they performed to a maximum capacity during training and were impressed by the staff's enthusiasm and encouragement. The patients felt that they were involved in the goal setting and the choice of treatment, and the staff noticed individual needs. There was a feeling among the patients of being acknowledged by the staff. Information about the disease was perceived as individualized. The climate and beautiful surroundings were viewed as encouraging physical activity and a feeling of well-being. Patients made new friends, had fun together and also shared experiences about their disease. Furthermore, the patients described a sense of belonging to a group as well as a feeling of not being the only one that was sick among the healthy. Not having to do everyday tasks and having time to themselves were perceived positively. Several factors contributed to the positive experiences of climate care; climate, environment, physical activity, social context, staff involvement, and information about the disease were described as interacting together and resulting in a sense of well-being. A proposal for future research would be to examine if/how the various factors might interact and affect the RA patients' illness and quality of life. PMID:26730385

  2. Rheumatoid arthritis patients’ experience of climate care

    PubMed Central

    Vaks, Katrin; Sjöström, Rita

    2015-01-01

    The purpose of this qualitative study was to understand and examine how patients with rheumatoid arthritis (RA) experience climate care and its effects. A qualitative approach was chosen for the study. Two men and six women were interviewed according to a semistructured interview guide. The text was analyzed using a manifest content analysis. The analysis resulted in four categories and 10 subcategories. The interviewees experienced climate care positively. The training was perceived increasing gradually. The patients felt that they performed to a maximum capacity during training and were impressed by the staff’s enthusiasm and encouragement. The patients felt that they were involved in the goal setting and the choice of treatment, and the staff noticed individual needs. There was a feeling among the patients of being acknowledged by the staff. Information about the disease was perceived as individualized. The climate and beautiful surroundings were viewed as encouraging physical activity and a feeling of well-being. Patients made new friends, had fun together and also shared experiences about their disease. Furthermore, the patients described a sense of belonging to a group as well as a feeling of not being the only one that was sick among the healthy. Not having to do everyday tasks and having time to themselves were perceived positively. Several factors contributed to the positive experiences of climate care; climate, environment, physical activity, social context, staff involvement, and information about the disease were described as interacting together and resulting in a sense of well-being. A proposal for future research would be to examine if/how the various factors might interact and affect the RA patients’ illness and quality of life. PMID:26730385

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

    PubMed Central

    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. PMID:26958193

  4. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

    NASA Astrophysics Data System (ADS)

    Trentham, David E.; Dynesius-Trentham, Roselynn A.; Orav, E. John; Combitchi, Daniel; Lorenzo, Carlos; Sewell, Kathryn Lea; Hafler, David A.; Weiner, Howard L.

    1993-09-01

    Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.

  5. Prevalence of rheumatoid arthritis in France: 2001

    PubMed Central

    Guillemin, F; Saraux, A; Guggenbuhl, P; Roux, C; Fardellone, P; Le Bihan, E; Cantagrel, A; Chary-Valckenaere, I; Euller-Ziegler, L; Flipo, R; Juvin, R; Behier, J; Fautrel, B; Masson, C; Coste, J

    2005-01-01

    Background: Prevalence estimates of rheumatoid arthritis (RA) vary across Europe. Recent estimates in southern European countries showed a lower prevalence than in northern countries. Objectives: To estimate the prevalence of RA in France in a multiregional representative sample in the year 2001. Methods: A two stage random sample was constituted in seven areas (20 counties) from the national telephone directory of households and by the next birthday method in each household. Patient-interviewers, member of self help groups, were trained to administer telephone surveys using a validated questionnaire for case detection of inflammatory rheumatism, and conducted the survey under quality control. All suspected cases of RA were confirmed by their rheumatologist or by clinical examination. Prevalence estimates after probability sampling correction were standardised for age and sex (national census 1999). Results: An average response rate of 64.7% (two stages combined) led to a total of 9395 respondents. Standardised prevalence was 0.31% (95% confidence interval 0.18 to 0.48) for RA, 0.51% in women and 0.09% in men, with a higher age-specific prevalence in the 65–74 year age band. A geographical analysis of county clustering showed significant variation across the country. Conclusion: This national multiregional cooperative study demonstrates the usefulness of working in association with patients of self help groups. It showed a similar prevalence of RA to that of the spondyloarthropathies estimated concomitantly during the survey. It provides a reliable basis for definition of population targets for healthcare delivery and drug treatments. PMID:15800010

  6. Smoking and overweight determine the likelihood of developing rheumatoid arthritis

    PubMed Central

    de Hair, Maria J H; Landewé, Robert B M; van de Sande, Marleen G H; van Schaardenburg, Dirkjan; van Baarsen, Lisa G M; Gerlag, Danielle M; Tak, Paul P

    2013-01-01

    Objectives Rheumatoid arthritis (RA) is a prototypic chronic inflammatory disease with a debilitating course if untreated. A genetic predisposition for RA is known, and its occurrence is associated with the presence of autoantibodies in the serum and with environmental factors. It is unknown if smoking and overweight are contributory factors for developing RA in individuals with RA-specific autoantibodies in the serum. Methods Fifty-five individuals at risk for developing RA, based on the pr