Weiss, Günter; Schett, Georg
Anaemia is frequently observed in patients with inflammatory rheumatic diseases. Depending on its severity, anaemia negatively affects cardiovascular performance, physical activity and the quality of life of patients. However, anaemia is considered to be a symptom of the underlying inflammatory disease and, thus, neglected as a complex medical condition that warrants specific diagnosis and treatment. Although inflammation-induced alterations in iron homeostasis and erythropoiesis have a dominant role in the pathogenesis of this type of anaemia, multiple other factors such as chronic blood loss, haemolysis, disease and treatment-associated adverse effects or vitamin deficiencies can also take part in the development of anaemia. Accordingly, the prevalence of anaemia is positively associated with the severity of the underlying disease. This Review will summarize epidemiological data on anaemia in inflammatory rheumatic diseases, along with a detailed description of underlying pathophysiological pathways, available diagnostic tools and practical diagnostic strategies. Discussion of established and newly emerging treatment regimens, as well as the need for further research in this clinically relevant field, will also be included.
Some inflammatory rheumatic diseases can involve the temporomandibular joint, such as rheumatoid arthritis and spondylarthritis. The aim of our work was to evaluate the current prevalence of these inflammatory TMJ diseases, to indicate the new therapeutics and to describe the collaboration between rheumatologist and maxillofacial surgeon in these pathologies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Inflammatory rheumatic diseases are generally multifaceted disorders and, therefore, measurement of multiple outcomes is relevant to most of these diseases. Developments in outcome measures in the rheumatic diseases are promoted by the development of successful treatments. Outcome measurement will increasingly deal with measurement of low levels of disease activity and avoidance of disease consequences. It is an advantage for patient management and knowledge transfer if the same outcomes are used in practice and in trials. Continuous measures of change are generally the most powerful and, therefore, are preferred as primary outcomes in trials. For daily clinical practice, outcome measures should reflect the patients' state and have to be easily derivable. The objective of this review is to describe recent developments in outcome measures for inflammatory rheumatic diseases for trials and clinical practice, with an emphasis on rheumatoid arthritis. PMID:19849821
Castañeda, Santos; Nurmohamed, Michael T; González-Gay, Miguel A
Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.
Rodríguez-Reyna, Tatiana Sofía; Martínez-Reyes, Cynthia; Yamamoto-Furusho, Jesús Kazúo
This article reviews the literature concerning rheumatic manifestations of inflammatory bowel disease (IBD), including common immune-mediated pathways, frequency, clinical course and therapy. Musculoskeletal complications are frequent and well-recognized manifestations in IBD, and affect up to 33% of patients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations, notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen presentation, aberrant recognition of self, the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues, and increased intestinal permeability. The response against microorganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic manifestations of IBD have been divided into peripheral arthritis, and axial involvement, including sacroiliitis, with or without spondylitis, similar to idiopathic ankylosing spondylitis. Other periarticular features can occur, including enthesopathy, tendonitis, clubbing, periostitis, and granulomatous lesions of joints and bones. Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The management of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation. Sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide should be used for selected indications. In some cases, tumor necrosis factor-alpha blocking agents should be considered as first-line therapy.
Malesci, D; Valentini, G; La Montagna, G
Toward the end of the last century a better knowledge of cardiovascular (CV) risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called "metabolic" or "insulin resistance syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO) and by The Third Report of The National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.
Semerano, Luca; Julia, Chantal; Aitisha, Ouidade; Boissier, Marie-Christophe
Nutrition is a major environmental influence on human health. Epidemiological and interventional studies suggest a pathophysiological or therapeutic role, respectively, for nutrition in inflammatory rheumatic diseases (IRDs). Nevertheless, the associations between nutrition and IRDs are often weak and inconsistent, and the available clinical trials on nutrition are methodologically flawed. Experimental evidence is accumulating that micronutrients in the diet may influence intestinal and systemic immune responses via complex interactions involving the gut microbiota. Micronutrients may, therefore, contribute to the pathogenesis of inflammatory diseases. No interventions targeting these interactions for diagnostic, prophylactic, or therapeutic purposes have been developed to date. Moreover, the relevance to human disease of experimental results obtained in animals or in vitro is unclear. Novel high-throughput technologies (-omics) may prove useful for a systems biology approach to these results that takes the complexity of the interactions into account. Concomitant cohort studies combining clinical and laboratory data collected over time may provide new impetus to research into the connections between nutrition and IRDs.
The main orofacial manifestation of the inflammatory rheumatic diseases is that of Sjögren's syndrome. In addition, there is a constellation of orofacial manifestations of the inflammatory rheumatic diseases, many of which are extra-articular with some constituting presenting signs of the underlying rheumatic disease. This review will discuss the orofacial manifestations in a variety of connective tissue diseases and will also allude to the oral adverse drug reactions that may occur as a consequence of therapy. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.
Cossermelli, W; Pastor, E H
Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.
Ballestar, Esteban; Li, Tianlu
Over the past decade, awareness of the importance of epigenetic alterations in the pathogenesis of rheumatic diseases has grown in parallel with a general recognition of the fundamental role of epigenetics in the regulation of gene expression. Large-scale efforts to generate genome-wide maps of epigenetic modifications in different cell types, as well as in physiological and pathological contexts, illustrate the increasing recognition of the relevance of epigenetics. To date, although several reports have demonstrated the occurrence of epigenetic alterations in a wide range of inflammatory rheumatic conditions, epigenomic information is rarely used in a clinical setting. By contrast, several epigenetic biomarkers and treatments are currently in use for personalized therapies in patients with cancer. This Review highlights advances from the past 5 years in the field of epigenetics and their application to inflammatory rheumatic diseases, delineating the future lines of development for a rational use of epigenetic information in clinical settings and in personalized medicine. These advances include the identification of epipolymorphisms associated with clinical outcomes, DNA methylation as a contributor to disease susceptibility in rheumatic conditions, the discovery of novel epigenetic mechanisms that modulate disease susceptibility and the development of new epigenetic therapies.
The current status of the use of biological medicine in the treatment of adult onset morbus still, Wegeners granulomatosis and systemic lupus erythematosus (SLE) is reviewed. The need for controlled trials is emphasized. Anti-CD20 treatment for SLE patients with kidney involvement and patients with Wegeners granulomatosis seems promising. Anti-TNF and IL1 receptor antagonist can control disease activity in most patients with adult morbus still.
Cuda, Carla M; Pope, Richard M; Perlman, Harris
Rheumatoid arthritis affects nearly 1% of the world's population and is a debilitating autoimmune condition that can result in joint destruction. During the past decade, inflammatory functions have been described for signalling molecules classically involved in apoptotic and non-apoptotic death pathways, including, but not limited to, Toll-like receptor signalling, inflammasome activation, cytokine production, macrophage polarization and antigen citrullination. In light of these remarkable advances in the understanding of inflammatory mechanisms of the death machinery, this Review provides a snapshot of the available evidence implicating death pathways, especially within the phagocyte populations of the innate immune system, in the perpetuation of rheumatoid arthritis and other rheumatic diseases. Elevated levels of signalling mediators of both extrinsic and intrinsic apoptosis, as well as the autophagy, are observed in the joints of patients with rheumatoid arthritis. Furthermore, risk polymorphisms are present in signalling molecules of the extrinsic apoptotic and autophagy death pathways. Although research into the mechanisms underlying these pathways has made considerable progress, this Review highlights areas where further investigation is particularly needed. This exploration is critical, as new discoveries in this field could lead to the development of novel therapies for rheumatoid arthritis and other rheumatic diseases.
Märker-Hermann, E; Bauer, H; Gromnica-Ihle, E
Rheumatic diseases can influence the reproduction, the course of pregnancy and the development of the fetus. The inflammatory rheumatic disease itself can be modulated in its activity in terms of amelioration or exacerbation of the rheumatic symptoms. The associations between rheumatic diseases and pregnancy will be illustrated with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus as examples. Antirheumatic drug therapy during pregnancy and the breast feeding period has to be adapted critically.
Guillot, Xavier; Tordi, Nicolas; Mourot, Laurent; Demougeot, Céline; Dugué, Benoît; Prati, Clément; Wendling, Daniel
The aim of this article was to review current evidence about cryotherapy in inflammatory rheumatic diseases (therapeutic and biological effects). For therapeutic effects, we performed a systematic review (PubMed, EMBASE, Cochrane Library, LILACS databases, unpublished data) and selected studies including non-operated and non-infected arthritic patients treated with local cryotherapy or whole-body cryotherapy. By pooling 6 studies including 257 rheumatoid arthritis (RA) patients, we showed a significant decrease in pain visual analogic scale (mm) and 28-joint disease activity score after chronic cryotherapy in RA patients. For molecular pathways, local cryotherapy induces an intrajoint temperature decrease, which might downregulate several mediators involved in joint inflammation and destruction (cytokines, cartilage-degrading enzymes, proangiogenic factors), but studies in RA are rare. Cryotherapy should be included in RA therapeutic strategies as an adjunct therapy, with potential corticosteroid and nonsteroidal anti-inflammatory drug dose-sparing effects. However, techniques and protocols should be more precisely defined in randomized controlled trials with stronger methodology.
Baumann Kurer, S; Seifert, B; Michel, B; Ruegg, R; Fehr, J
We prospectively studied 45 anaemic patients (37 women, 8 men) with chronic inflammatory rheumatic diseases. The combination of serum ferritin and CRP (as well as ESR) in its predictive capacity for bone marrow iron stores was examined. The relationship between other iron-related measurements (transferrin, transferrin saturation, soluble transferrin receptor, erythrocyte porphyrins and percentage of hypochromic/microcytic erythrocytes) and bone marrow iron stores was also investigated. Stainable bone marrow iron was taken as the most suitable standard to separate iron-deficient from iron-replete patients. 14 patients (31%) were lacking bone marrow iron. Regression analysis showed a good correlation between ferritin and bone marrow iron (adjusted R2 = 0.721, P < 0.0001). The combination of ferritin and CRP (ESR) did not improve the predictive power for bone marrow iron (adjusted R2 = 0.715) in this cohort of patients with low systemic inflammatory activity. With respect to the bone marrow iron content the best predictive cut-off value of ferritin was 30 micrograms/l (86% sensitivity, 90% specificity). The other iron-related parameters both individually and when combined were less powerful in predicting bone marrow iron than ferritin alone. Only zinc bound erythrocyte protoporphyrin in combination with ferritin slightly improved prediction (adjusted R2 = 0.731). A cut-off point of 11% hypochromic erythrocytes reached a high specificity (90%), but was less sensitive (77%).
Dessein, Patrick H; Solomon, Ahmed; Hollan, Ivana
Patients with rheumatoid arthritis (RA) experience an increased cardiometabolic risk factor burden that is substantially driven by systemic inflammation. This occurs less consistently in patients with ankylosing spondylitis (AS). Psoriatic arthritis most strongly associates with excess adiposity and metabolic risk. RA patients also often have systemic inflammation-induced proinflammatory high-density lipoprotein (HDL) cholesterol particles and lean/muscle mass loss in association with increased adiposity, a condition termed rheumatoid cachexia, which further enhances cardiovascular risk. The presence of proinflammatory HDL and lean mass loss was also reported in patients with AS. Individualized aerobic and resistance exercise programs can improve body composition and metabolic risk factor profiles in RA and AS. Future studies should assess how long-term lifestyle changes can be effectuated and if these can influence cardiovascular events in inflammatory rheumatic diseases. Herein, we review the current evidence on metabolic abnormalities in inflammatory arthritis. We propose management strategies and a research agenda. Copyright © 2016 Elsevier Ltd. All rights reserved.
Cuda, Carla M.; Pope, Richard M.; Perlman, Harris
Rheumatoid arthritis affects nearly 1% of the world's population and is a debilitating autoimmune condition that can result in joint destruction. During the past decade, inflammatory functions have been described for signalling molecules classically involved in apoptotic and non-apoptotic death pathways, including but not limited to toll-like receptor signalling, inflammasome activation, cytokine production, macrophage polarization and antigen citrullination. In light of these remarkable advances in the understanding of inflammatory mechanisms of the death machinery, this review provides a snapshot of the available evidence implicating death pathways, especially within the phagocyte populations of the innate immune system, in the perpetuation of rheumatoid arthritis. Elevated levels of signalling mediators of both the extrinsic and intrinsic apoptotic as well as the autophagy death pathways are observed in the joints of patients with rheumatoid arthritis. Furthermore, in rheumatoid arthritis patients, risk polymorphisms are present in signalling molecules of the extrinsic apoptotic and autophagy death pathways. Although research into the mechanisms underlying these death pathways has made considerable progress, this review highlights areas where further investigation is particularly needed. This exploration is critical, as new discoveries in this field could lead to the development of novel therapeutic targets for rheumatoid arthritis and other rheumatic diseases. PMID:27549026
Graf, S; Schumm-Draeger, P-M
New studies have demonstrated similarities in the complex pathomechanisms of diabetes mellitus type 1 (T₁D) and rheumatic diseases and in particular rheumatoid arthritis (RA). Common HLA gene complex characteristics and polymorphisms of inflammatory cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play a special role in both disorders. The metabolic syndrome, associated with insulin resistance and diabetes mellitus type 2 (T₂D), often shows criteria of a subclinical chronic inflammation. New forms of therapy with monoclonal antibodies against TNF-α, IL-1 and IL-6 have improved the management of patients with RA. Cytokine-induced inflammation also seems to be important in the pathogenesis and progression of T₁D and T₂D. Whether a therapy with the same monoclonal antibodies established in RA could also be successful in diabetes still has to be investigated in further studies. Both RA and T₁D are autoimmune disorders and show a cumulative incidence with further autoimmune diseases.
Bühler, Silja; Eperon, Gilles; Ribi, Camillo; Kyburz, Diego; van Gompel, Fons; Visser, Leo G; Siegrist, Claire-Anne; Hatz, Christoph
The number of individuals with autoimmune inflammatory rheumatic diseases (AIIRDs) treated with immunosuppressive drugs is increasing steadily. The variety of immunosuppressive drugs and, in particular, biological therapies is also rising. The immunosuppressants, as well as the AIIRD itself, increase the risk of infection in this population. Thus, preventing infections by means of vaccination is of utmost importance. New Swiss vaccination recommendations for AIIRD patients were initiated by the Swiss Federal Office of Public Health and prepared by a working group of the Federal Commission for Vaccination Issues as well as by consultation of international experts. A literature search was performed in electronic databases (Cochrane, Medline, PubMed, Embase). In addition, unpublished literature was identified through a targeted website search of relevant organisations and international conferences dealing with vaccination, infectious diseases and rheumatology. Although data are scarce, the following main points were retrieved from the literature. Inactivated vaccines are safe, but their immunogenicity may be reduced in AIIRD patients, especially if they are under immunosuppressive therapy. Rituximab and abatacept appear to reduce significantly immune responses after vaccination. Live vaccines are generally contraindicated under immunosuppressive therapy owing to safety concerns. Specific exceptions, as well as time intervals for the administration of live vaccines after interruption of an immunosuppressive therapy, have been formulated in this article. More evidence regarding the immunogenicity and safety of vaccinations in AIIRD patients under various therapies is needed. Vaccination recommendations should be updated on a regular basis, as more scientific data will become available.
Yu, Kuang-Hui; Kuo, Chang-Fu; Huang, Lu Hsiang; Huang, Wen-Kuan; See, Lai-Chu
Abstract The aim of this study was to determine whether inflammation is related to cancer development, and whether the incidence of cancer is increased and occurs in a site-specific manner in patients with systemic autoimmune rheumatic diseases (SARDs). This study included a nationwide dynamic cohort of patients with various newly diagnosed SARDs from 1997 to 2010 with follow-up until 2012. This study included 75,123 patients with SARDs. During 562,870 person-years of follow-up, 2844 patients developed cancer. Between 1997 and 2010, the highest number of newly diagnosed SARDs cases were rheumatoid arthritis (n = 35,182), followed by systemic lupus erythematosus (SLE, n = 15,623), Sjögren syndrome (n = 11,998), Kawasaki disease (n = 3469), inflammatory bowel disease (n = 2853), scleroderma (n = 1814), Behçet disease (n = 1620), dermatomyositis (n = 1119), polymyositis (n = 811), and vasculitis other than Kawasaki disease (n = 644). A significant standardized incidence ratio (SIR) of overall cancer was observed for patients with SLE (1.41; 95% confidence interval [CI], 1.28–1.56), Sjögren syndrome (1.19; 95% CI, 1.08–1.30), scleroderma (1.27; 95% CI, 1.02–1.59), dermatomyositis (4.79; 95% CI, 4.01–5.73), polymyositis (1.47; 95% CI, 1.05–2.06), vasculitis excluding Kawasaki disease (1.75; 95% CI, 1.20–2.55), and Kawasaki disease (2.88; 95% CI, 1.60–5.20). Overall, patients with most SARDs had a significantly higher risk of inflammation-associated site-specific cancers and hematologic malignancies. This study confirms that autoimmunity is associated with site-specific and hematological malignancies and provides clinical evidence of an association between inflammation and subsequent site-specific cancer development. These findings support the importance of inflammation in site-specific organ system carcinogenesis. PMID:27149461
Ankle involvement is frequent in patients with inflammatory rheumatic diseases, but accurate evaluation by physical examination is often difficult because of the complex anatomical structures of the ankle. Over the last decade, ultrasound (US) has become a practical imaging tool for the assessment of articular and periarticular pathologies, including joint synovitis, tenosynovitis, and enthesitis in rheumatic diseases. Progress in power Doppler (PD) technology has enabled evaluation of the strength of ongoing inflammation. PDUS is very useful for identifying the location and kind of pathologies in rheumatic ankles as well as for distinguishing between inflammatory processes and degenerative changes or between active inflammation and residual damage. The aim of this paper is to illustrate the US assessment of ankle lesions in patients with inflammatory rheumatic diseases, including rheumatoid arthritis, spondyloarthritis, and systemic lupus erythematosus, focusing on the utility of PDUS.
Ankle involvement is frequent in patients with inflammatory rheumatic diseases, but accurate evaluation by physical examination is often difficult because of the complex anatomical structures of the ankle. Over the last decade, ultrasound (US) has become a practical imaging tool for the assessment of articular and periarticular pathologies, including joint synovitis, tenosynovitis, and enthesitis in rheumatic diseases. Progress in power Doppler (PD) technology has enabled evaluation of the strength of ongoing inflammation. PDUS is very useful for identifying the location and kind of pathologies in rheumatic ankles as well as for distinguishing between inflammatory processes and degenerative changes or between active inflammation and residual damage. The aim of this paper is to illustrate the US assessment of ankle lesions in patients with inflammatory rheumatic diseases, including rheumatoid arthritis, spondyloarthritis, and systemic lupus erythematosus, focusing on the utility of PDUS. PMID:25405085
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Gremese, Elisa; Tolusso, Barbara; Gigante, Maria Rita; Ferraccioli, Gianfranco
The growing body of evidence recognizing the adipose tissue (AT) as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders, together with the global epidemic of overweight and obesity, rise obesity as a hot topic of current research. The chronic state of low-grade inflammation present in the obese condition and the multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of several inflammatory conditions including rheumatic autoimmune and inflammatory diseases. We will discuss the main relevant evidences on the role of the AT on immune and inflammatory networks and the more recent evidences regarding the effects of obesity on the incidence and outcomes of the major autoimmune chronic inflammatory diseases. PMID:25426122
The treatment of inflammatory rheumatic diseases, such as rheumatoid arthritis, spondylitis ankylosans and systemic lupus erythematosus, is improving continuously. This has lead to an increasing number of young patients with a wish to have children. Greater insight into the course of rheumatic diseases during pregnancy and post partum has enabled optimized support for women with rheumatic diseases wishing to have children. To ensure a favorable outcome, pregnancy should be started during a period of disease stability and should be monitored closely. A careful assessment of possible risks and the justified use of antirheumatic drugs before, during and after pregnancy are key issues for success.
Sales, C; Oliviero, F; Spinella, P
The Mediterranean diet is based on a pattern of eating closely tied to the Mediterranean region, which includes Greece and southern Italy. Essentially, the traditional diet emphasizes foods from plant sources, limited meat consumption, small amounts of wine and olive oil as the main fat source. The beneficial effects of the Mediterranean diet has been proven not only to cardiovascular diseases but also for diabetes, obesity, arthritis and cancer. Its anti-inflammatory and protective properties are linked to the large presence of omega-3 polyunsaturated fatty acids, vitamins, but especially to the constituents of extra virgin olive oil: oleic acid, phenolic compounds olecanthal, a new recently discovered molecule, with natural anti-inflammatory properties. It has been shown that the Mediterranean diet can reduce disease activity, pain and stiffness in patients with inflammatory arthritis and may thus constitute a valuable support for patients suffering from these diseases.
Perez-Alamino, Rodolfo; Maldonado-Ficco, Hernan; Maldonado-Cocco, José A
Musculoskeletal symptoms are the most frequent extra-intestinal manifestations of inflammatory bowel disease (IBD), ranging between 10 and 40 % of cases. Pathogenesis is still unclear, although several factors have been associated (genetic, environmental, and immunologic pathways). Rheumatic manifestations in IBD patients are heterogeneous, including axial and peripheral involvement, dactylitis, enthesitis, uveitis, as well as skin involvement. Currently, magnetic resonance imaging and ultrasonography are important tools for detecting early pathological changes in IBD patients with suspected rheumatic disease. New advances into the genetics and pathophysiology have provided more effective and targeted therapy for IBD patients with rheumatic manifestations. Given the high prevalence, awareness of the musculoskeletal symptoms is essential to avoid a misdiagnosis. Finally, an interdisciplinary approach of IBD patients, including rheumatologist and gastroenterologist, will improve the quality of life these patients.
Beuthan, Juergen; Prapavat, Viravuth; Naber, Rolf-Dieter; Minet, Olaf; Mueller, Gerhard J.
Rheumatoid arthritis (RA) is a common inflammatory disease of interphalangeal joints. The utilization of conventional imaging systems (e.g. x-rays) for non invasive diagnostics at an early stage of the disease is difficult, since pathologically induced changes do not occur at this stage in hard tissue. Use of MR and ultrasound methods are both methodically problematic and expensive. Therefore investigations for optical diagnostics using photon density waves (PDW) were carried out. The PDW was realized with an intensity modulated laser diode (825 nm, fmod: 110 MHz) and an ac- and phase detection in a 2D transillumination scanner. Measurements of optical properties of synovia and synovialis of healthy and early RA stages were performed and indicated a significant pathological increase of (mu) s. The detected PDW-pictures provided corresponding results. Further investigations regarding the object- variation of the modulation transfer function provide a sufficient spatial resolution in order to assign functional changes to anatomical structures. The results are presented using photos.
Peretz, A; Nève, J; Jeghers, O; Pelen, F
The effects of zinc supplementation on zinc status and on clinical and biological indicators of inflammation were investigated in 18 patients with chronic inflammatory rheumatic diseases and in 9 healthy control subjects. Patients with mild and recent onset disease were assigned to a 60-d trial to receive either 45 mg Zn (as gluconate)/d or a placebo, while control subjects received the zinc supplement. Baseline mean plasma zinc of the patients was low whereas mononuclear cell zinc content was elevated, suggesting a redistribution of the element related to the inflammatory process rather than to a zinc-deficient state. Zinc supplementation increased plasma zinc to a similar extent in patients and in control subjects, which suggested no impairment of zinc intestinal absorption as a result of the inflammatory process. On the contrary, erythrocyte and leukocyte zinc concentrations were not modified in the two groups examined. No beneficial effect of zinc treatment could be demonstrated on either clinical or inflammation indexes.
Gayed, M; Gordon, C
Pregnancy is an issue that should be discussed with all patients with rheumatic diseases who are in the reproductive age group. Infertility is rarely due to the disease but can be associated with cyclophosphamide therapy. Most rheumatic diseases that are well controlled prior to pregnancy do not deteriorate in pregnancy, providing that the patient continues with appropriate disease-modifying therapy. Some patients with inflammatory arthritis go in to remission during pregnancy. Patients with renal involvement may be at increased risk of disease flare. This needs to be distinguished from pre-eclampsia. Intrauterine growth restriction is more likely in patients with active systemic disease, hypertension, a history of thrombosis and renal involvement. Premature delivery may need to be planned to reduce the risks of stillbirth and can be associated with a variety of neonatal complications. Post-partum flare is common in all the rheumatic diseases.
Bojke, Laura; Spackman, Eldon; Hinde, Sebastian; Helliwell, Philip
Inflammatory rheumatic diseases are common. It is estimated that ∼2.1% of the population has an inflammatory rheumatic disease (Andrianakos A, Trontzas P, Christoyannis F et al. Prevalence of rheumatic diseases in Greece: a cross-sectional population based epidemiological study. The ESORDIG Study. J Rheumatol 2003;30:1589-601). For diseases such as RA, PsA and AS, onset is most frequent between the ages of 30 and 50 years. The impact of inflammatory rheumatic diseases on physical functioning can be significant. Patients can suffer from swollen joints that cause pain and disability. This can reduce sufferers' ability to lead fully productive lives. This has major financial consequences for sufferers and their families and there is an economic impact on society. The National Institute for Health and Clinical Excellence (NICE) technology appraisal process has typically ignored any improvements in productivity that may result from treatment. There have been calls to extend the perspective of economic evaluations to include productivity costs as one aspect of wider social effects. However, there are a number of issues that must be resolved before productivity costs can become a routine input into the calculation of cost-effectiveness of treatments. First, there is limited agreement regarding the practical details and appropriate methods for their inclusion in economic evaluation. Second, there are issues that must be addressed regarding society's preference for equity. This issue arises when considering individual's economic productivity, that is to say, how we weigh individuals who are more productive (e.g. those in employment) against those who are less so (e.g. the unemployed). Finally, it is important to consider cross-budgetary effects, since productivity has cost and benefit implications outside of health.
Richter, J G; Becker, A; Specker, C; Monser, R; Schneider, M
On behalf of the "systemic inflammatory rheumatic diseases network" comprehensive, nationwide horizontal and vertical cross-linking of research and care is to be developed for the first time. The quality of scientific work and patient care is to be increased in the medium term through this improved communication and co-operation. Our objective was to determine what hardware and software are available to the patients involved, with a view to the Internet being used as a basis for communication. The ultimate aim was to provide patients with an adequate source of information on care. A survey was carried out among 400 patients attending our outpatient clinics. Data on the hardware and software used and on Internet access and patterns and degree of utilization were collected using a unilateral questionnaire. 326 patients filled in the questionnaire. 163 of those responding had Internet access, with younger and better educated patients using the Internet significantly more frequently. No dependency was noted on gender or marital status. Mean time duration for Internet use was longer in men. 55.8% of the internet users searched for medical questions. Major search topics included up to date therapeutic options (46.6%) and information on specific diseases (28.8%). Internet is an important information medium for patients. Technical requirements and high motivation make communication practicable for about 50% of patients. To ensure acceptance, the Internet platform of the systemic inflammatory rheumatic diseases network needs to be aligned to patients' requirements, bearing in mind the need for extensive high-value, reliable scientific information to be offered on the website.
Kamradt, T; Radbruch, A; Chang, H-D
The Research Consortium IMPAM (IMprinting of the PAthogenic Memory for rheumatic inflammation) has recently been funded by the Federal Ministry of Education and Research in Germany. Within this consortium ten different research groups, coordinated by the German Rheumatism Research Center (DRFZ) and the University Hospital Jena, will examine the molecular dialogue between immune system memory cells and mesenchymal cells in chronic rheumatic diseases, such as rheumatoid arthritis or ankylosing spondylitis. The consortium's aim is to understand and modulate these interactions therapeutically, such that the pathogenic imprinting of proinflammatory memory cells can be extinguished and the anti-inflammatory capacity of the patients' regulatory cells can be restored.
Li, Jun; Hsu, Hui-Chen; Mountz, John D.
The synovial tissue of Rheumatoid Arthritis (RA) patients is enriched with macrophages and T lymphocytes which are two central players in the pathogenesis of RA. Interaction between myeloid cells and T cells are essential for the initiation and progression of the inflammatory processes in the synovium. With the rapid evolution of our understanding of how these two cell types are involved in the regulation of immune responses, RA is emerging as an ideal disease model for investigating the cell-cell interactions and consequently introducing novel biologic agents that are designed to disrupt these processes. This review will discuss the bidirectional interaction between the IL-23+ inflammatory macrophages and IL-17+ GM-CSF+ CD4 T cells in rheumatic diseases as well as potential antirheumatic strategies via apoptosis induction in this context. PMID:25309946
Marouen, Sarah; Barnetche, Thomas; Combe, Bernard; Morel, Jacques; Daïen, Claire I
To assess body composition of patients with inflammatory rheumatic disease and the effect of TNF inhibitors on it. This was systematic review with meta-analysis of studies consulted on PubMed, Cochrane Library and EMBASE and assessing body composition in patients with rheumatoid arthritis or spondyloarthritis. We compared i) patients with healthy controls and ii) body components before and after TNF inhibitors. Among the 703 articles reviewed, 19 met the inclusion criteria. In patients with rheumatoid arthritis, a significant increase in fat mass (+1.85 kg, p=0.02), adiposity (+3.53%, p<0.00001) and android mass (+1.7 kg, p<0.00001) and a significant decrease in lean mass (-3.03 kg, p=0.01), were observed. In patients with spondyloarthritis, a significant but modest increase in fat mass (+0.69 kg, p=0.03) and a significant decrease in lean mass (-3.74 kg, p=0.03) were observed. Nine studies assessed impact of TNF inhibitors on body composition, with an increase of fat mass in the short and long term in all studies. Data on lean mass were controversial. Two studies found an increase in visceral or android mass under TNF inhibitors. Patients with inflammatory rheumatic disease have a significant decrease in lean mass and increase in fat mass. The use of TNF inhibitors is associated with a further increase in fat mass including android fat, which could potentially have cardiovascular consequences.
Wong, Peter Kk; Bagga, Hanish; Barrett, Claire; Hanrahan, Paddy; Johnson, Doug; Katrib, Amel; Leder, Karin; Marabani, Mona; Pentony, Peta; Riordan, John; White, Ray; Young, Laurel
Autoimmune inflammatory rheumatic diseases (AIIRD) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are often complicated by infection, which results in significant morbidity and mortality. The increased risk of infection is probably due to a combination of immunosuppressive effects of the AIIRD, comorbidities, and the use of immunosuppressive conventional synthetic disease modifying anti-rheumatic drugs (DMARDS) and more recently, targeted synthetic DMARDS and biologic DMARDS which block specific pro-inflammatory enzymes, cytokines or cell types. The use of these various DMARDS has revolutionized the treatment of AIIRD. This has led to a marked improvement in quality of life for AIIRD patients, who often now travel for prolonged periods. Many infections are preventable with vaccination. However, as protective immune responses induced by vaccination may be impaired by immunosuppression, where possible, vaccination may need to be performed prior to initiation of immunosuppression. Vaccination status should also be reviewed when planning overseas travel. Limited data regarding vaccine efficacy in patients with AIIRD makes prescriptive guidelines difficult. However, a vaccination history should be part of the initial work-up in all AIIRD patients. Those caring for AIIRD patients should regularly consider vaccination to prevent infection within the practicalities of routine clinical practice.
Akdoğan, Ali; Okutucu, Sercan; Kılıç, Levent; Kaya, Barış; Evranos, Banu; Aytemir, Kudret; Çöplü, Lütfi; Ertenli, İhsan; Çalgüneri, Meral; Oto, Ali; Tokgözoğlu, Lale
Objective Pulmonary arterial hypertension (PAH) is a devastating complication of inflammatory rheumatic diseases. The aim of this study was to determine the role of screening for the early diagnosis of pulmonary hypertension (PH) in inflammatory rheumatic diseases. Material and Methods Data of patients with inflammatory rheumatic diseases and PH who had no obvious cause of PH and who were evaluated by Working Group for Pulmonary Hypertension in Hacettepe University were investigated retrospectively. All patients with inflammatory disease were evaluated by right heart catheterization (RHC) to check if they had systolic pulmonary arterial pressure (sPAP) ≥40 mmHg and/or symptoms related to PH unless explained by other causes. Results RHC was performed in 47 patients with inflammatory rheumatic diseases and PH out of 50 patients who were to be evaluated by RHC based on clinical and Doppler echocardiographic findings. There was a positive correlation between sPAP estimated by Doppler echocardiography and sPAP determined by RHC in patients with inflammatory rheumatic diseases (r=0.66; p<0.001). The mean pulmonary arterial pressure (mPAP) was found to be <25 mmHg in 27.7% of the patients. New York Heart Association functional capacity (NYHA FC) was class III or IV in 79.0% of the patients with PAH. PAH was more frequent in patients with NYHA FC III–IV compared with patients with NYHA FC I–II [58.7% (15) patients vs. 19.0% (4) patients; p=0.009]. Conclusion In this study, approximately 80% of the patients with inflammatory disease-associated PAH were diagnosed late in NYHA FC III or IV. There are still unresolved issues in the diagnosis and treatment of PH in inflammatory diseases. Collaboration and multidisciplinary approach are the key points to overcome the challenges in this field. PMID:27708911
Bijl, M; Agmon-Levin, N; Dayer, J-M; Israeli, E; Gatto, M; Shoenfeld, Y
Will vaccination raise the incidence of autoimmune diseases, what is the impact of increasingly crowded vaccination schedules, the vaccination in age groups and the risk of coincidental temporal association? All these issues are still under debate. However, for the time being, to avoid confusion in the medical community and the media, we have to adhere to guidelines established consensually by experts while ensuring a strict surveillance and reporting possible side effects. Recommendation for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD) based on the currently available evidence and expert opinion were recently formulated by an EULAR task force. Major recommendations for AIIRD include: i) vaccination should ideally be administered during stable disease; ii) influenza vaccination and pneumococcal vaccination should be strongly considered; iii) vaccination can be administered during the use of DMARDs and TNF-inhibitors, but before starting rituximab; iv) live attenuated vaccines should be avoided whenever possible in immunosuppressed patients; v) BCG vaccination is not recommended.
Bartlett, Susan J.; Haaz, Steffany; Mill, Christopher; Bernatsky, Sasha; Bingham, Clifton O.
Yoga is a popular activity which may be well suited for some individuals with certain rheumatic disorders. Regular yoga practice can increase muscle strength and endurance, proprioception and balance, with emphasis on movement through a full range of motion to increase flexibility and mobility. Additional beneficial elements of yoga include breathing, relaxation, body awareness and meditation, which can reduce stress and anxiety and promote a sense of calmness, general well-being and improved quality of life. Yoga also encourages a meditative focus, increased body awareness and mindfulness; some evidence suggests yoga may help decrease inflammatory mediators including C-reactive protein and interleukin-6. Yoga is best learned under the supervision of qualified teachers who are well informed about the potential musculoskeletal needs of each individual. Here, we briefly review the literature on yoga in healthy, musculoskeletal, and rheumatic disease populations and offer recommendations for discussing ways to begin yoga with patients. PMID:24173693
Bramlage, Carsten Paul; Froelich, Britta; Wallbach, Manuel; Minguet, Joan; Grupp, Clemens; Deutsch, Cornelia; Bramlage, Peter; Koziolek, Michael; Müller, Gerhard Anton
In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p < 0.001; λ, r = 0.398, p < 0.001) and erythrocyte sedimentation rate (κ, r = 0.692, p < 0.001; λ, r = 0.612, p < 0.001). Patients being treated with rituximab displayed FLC levels similar to those of the reference group. There were clear elevations in both κ and λ FLCs in patients with rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.
Rossini, M; Gatti, D; Viapiana, O; Caimmi, C; Idolazzi, L; Fracassi, E; Adami, S
Vitamin D has some well-known effects on calcium, phosphate and bone metabolism, but it has recently shown to have many other effects, which may potentially be relevant to patients with extra-skeletal rheumatic diseases. Such effects may be justified by: 1) the presence of the vitamin D receptors also on extra-osseous cells, such as cartilage cells, sinoviocytes, muscle cells; 2) the proven role of vitamin D in the control of the transcription of genes involved in rheumatic diseases; 3) the evidence that vitamin D has multiple endocrine effects not only on calcium homeostasis; 4) the activation of vitamin D not only in the kidneys, but also in monocyte-macrophage and lymphocytic cell lines and in some epithelial cells with additional intracrine and paracrine effects. Vitamin D deficiency has been reported in numerous metabolic, degenerative, inflammatory and autoimmune rheumatic diseases. In some cases this association was also related to the risk of developing a rheumatic disease or the degree of disease activity. However there is no conclusive evidence of the efficacy of a preventive or therapeutic strategy based on vitamin D supplementation in extra-skeletal rheumatic diseases. This review aims to provide an overview of the latest evidence concerning the relationship between vitamin D and the most relevant rheumatic diseases.
BOJINCA, Violeta; JANTA, Iustina
ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments. PMID:23482881
Santos, Maria José; Fonseca, João Eurico
Cardiovascular (CV) events are among the leading causes of morbidity and mortality in patients with inflammatory rheumatic diseases. It has been hypothesized that, in addition to the traditional CV risk factors, inflammation is a major contributor to atherogenesis. Metabolic syndrome (MetS) stands for a cluster of risk factors associated with insulin resistance and increased abdominal fat. Inflammation and MetS are intimately linked. Inflammatory biomarkers are frequently elevated in people with MetS and, conversely, the prevalence of MetS is higher in patients with chronic inflammatory rheumatic diseases, such as Rheumatoid Arthritis and Systemic Lupus Erythematosus. Inflammatory cytokines impair insulin sensitivity and can induce an adverse lipoprotein profile as seen in MetS. Furthermore, the presence of MetS correlates with increased subclinical atherosclerosis, major adverse CV events and death, making an important contribution to the CV burden in inflammatory diseases. Adipose tissue has recently emerged as an active organ that produces and secretes numerous mediators - adipokines - particularly relevant in energy homeostasis, inflammation, immune regulation and angiogenesis. These mediators arise as a potential link between MetS, inflammation and atherogenesis. Understanding the complex regulation and function of adipokines in health and disease is a priority since it may lead to new preventive and therapeutic interventions aiming to decrease CV risk.
Ben-Zvi, Ilan; Goldenberg, Ilan; Matetzky, Shlomi; Grossman, Chagai; Elis, Avishay; Gavrielov-Yusim, Natalie; Livneh, Avi
Patients with inflammatory rheumatic diseases (IRD) have a high burden of cardiovascular disease (CVD), leading to increased mortality and morbidity. However, it is not clear whether increased CVD mortality in IRD is due to a higher incidence or worse outcome of cardiovascular events (higher case fatality). In this observational case-control study, we assessed the outcome of acute coronary syndrome (ACS) in patients with IRDs compared to matched controls without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS), a large, national, real-life registry detailing the extent, severity, and outcome of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified with IRD, including 11 patients with rheumatoid arthritis, five patients with systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis (AS), and one patient with psoriatic arthritis (PsA). The study patients were compared to 120 matched control patients (adjusted for age and risk factors for CVD) without IRD. Compared to controls, IRD patients had similar clinical presentation and similar type of ACS and received identical initial treatment at the ER. The two groups had comparable rates of complications including major adverse cardiovascular events (death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis) (10 vs. 11.7% in the study and control group, respectively, p > 0.05), re-hospitalization (20 vs. 21.1%, respectively, p > 0.05), and severe congestive heart failure (7.7 vs. 6.9%, respectively, p > 0.05) within 30 days. The outcome and prognosis of ACS in patients with IRD is not worse than that of control, supporting the higher prevalence of CVD in this population as the cause for their excess mortality.
... Spondylitis, Q&A Bursitis and Tendinitis, Q&A Fibromyalgia, Q&A Gout, Q&A Juvenile Arthritis, Q& ... role. For example, lupus, rheumatoid arthritis, scleroderma, and fibromyalgia are more common among women. Other Rheumatic Diseases ...
Urruticoechea-Arana, Ana; Martín-Martínez, María A; Castañeda, Santos; Piedra, Carlos A Sanchez; González-Juanatey, Carlos; Llorca, Javier; Díaz-Gonzalez, Federico; González-Gay, Miguel A
The aim was to study the association between 25-hydroxyvitamin D (25(OH)D) levels and the clinical characteristics of patients with chronic inflammatory rheumatic diseases (CIRD). We studied a cross-section from the baseline visit of the CARMA project (CARdiovascular in rheuMAtology), a 10-year prospective study evaluating the risk of cardiovascular events in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients, and non-CIRD patients who attended rheumatology outpatient clinics from 67 hospitals in Spain. Non-CIRD group was frequency matched by age with the joint distribution of the three CIRD groups included in the study. 25(OH)D deficiency was defined if 25(OH)D vitamin levels were < 20 ng/ml. 2.234 patients (775 RA, 738 AS and 721 PsA) and 677 non-CIRD subjects were assessed. The median (p25-p75) 25(OH)D levels were: 20.4 (14.4-29.2) ng/ml in RA, 20.9 (13.1-29.0) in AS, 20.0 (14.0-28.8) in PsA, and 24.8 (18.4-32.6) ng/ml in non-CIRD patients. We detected 25(OH)D deficiency in 40.5 % RA, 39.7 % AS, 40.9 % PsA and 26.7 % non-CIRD controls (p < 0.001). A statistically significant positive association between RA and 25(OH)D deficiency was found (adjusted (adj.) OR = 1.46; 95 % CI = 1.09-1.96); p = 0.012. This positive association did not reach statistical significance for AS (adj. OR 1.23; 95 % CI = 0.85-1.80) and PsA (adj. OR 1.32; 95 % CI = 0.94-1.84). When the parameters of disease activity, severity or functional impairment were assessed, a marginally significant association between 25(OH)D deficiency and ACPA positivity in RA patients (adj. OR = 1.45; 95 % CI = 0.99-2.12; p = 0.056), and between 25(OH)D deficiency and BASFI in AS patients (adj. OR = 1.08; 95 % CI = 0.99-1.17); p = 0.07) was also found. Patients with RA show an increased risk of having 25(OH)D deficiency compared to non-CIRD controls.
Heyll, Uwe; Münnich, Uwe; Senger, Volker
The comparably high number of severe side effects due to treatment with nonsteroidal anti-inflammatory drugs (NSAID) calls for better tolerated substances. One possible alternative is seen in the systemic treatment with proteolytic enzyme preparations for oral administration. The aim of this study was to determine whether the results from controlled randomized trials on enzyme therapy prove equal anti-inflammatory effectiveness compared to NSAID in the treatment of degenerative or inflammatory rheumatic disease. All drug preparations registered in Germany as having anti-inflammatory properties were listed. Among these preparations, a systematic search was carried out for randomized clinical therapeutic trials giving evidence for the anti-inflammatory effectiveness of enzyme preparations or their components. The anti-inflammatory effectiveness of three out of eight registered enzyme preparations was investigated in randomized trials. In total, seven trials were judged to be sufficiently documented and to allow valuation. All studies show severe methodical deficits, and the standard trial design (clinical trials during inpatient rehabilitation in combination with extensive accompanying treatment) does not allow clear-cut conclusions. According to the present state of knowledge, oral proteolytic enzyme treatment does not offer a justified alternative in comparison with NSAID in the anti-inflammatory treatment of rheumatic disease.
Fatigue is a common symptom in a large number of medical and psychological disorders including many rheumatologic illnesses. A frequent question for health care providers is related to whether reported fatigue is “in the mind” or “in the body” i.e. central or peripheral. If fatigue occurs at rest without any exertion this suggests psychological or central origins. If patients relate their fatigue mostly to physical activities including exercise then their symptoms can be considered peripheral. However, most fatiguing syndromes seem to depend on both peripheral and central mechanisms. Sometimes muscle biopsy with histochemistry may be necessary for the appropriate tissue diagnosis whereas serological tests generally provide little reliable information about the origin of muscle fatigue. Muscle function and peripheral fatigue can be quantified by contractile force and action potential measurements whereas validated questionnaires are frequently used for assessment of mental fatigue. Fatigue is a hallmark of many rheumatologic conditions including fibromyalgia, myalgic encephalitis/chronic fatigue syndrome, rheumatoid arthritis, systemic lupus, Sjogren’s syndrome and ankylosing spondylitis. Whereas many studies have focused on disease activity as a correlate to these patients’ fatigue it has become apparent that other factors including negative affect and pain are some of the most powerful predictors for fatigue. Conversely sleep problems, including insomnia seem to be less important for fatigue. There are several effective treatment strategies available for fatigued patients with rheumatologic disorders including pharmacological and non-pharmacological therapies PMID:22802155
Genc, Hakan; Duyur Cakit, Burcu; Nacir, Baris; Saracoglu, Meryem; Kacar, Mahmut; Erdem, Hatice Rana
The aim of this study was to evaluate the effects of a 1-year course of sulfasalazine monotherapy on enthesal abnormalities of inflammatory rheumatic diseases (IRDs) using ultrasonography. Thirty-six patients with IRD including 20 patients with rheumatoid arthritis (RA) and 16 patients with ankylosing spondylitis (AS) (22 women, 14 men, mean ages 43.3 +/- 8.8 years), and 18 healthy controls (10 women, 8 men, mean ages 42.5 +/- 9.9 years) matched by age and body mass index were enrolled in this study. For the evaluation of enthesal structures, all patients and controls underwent ultrasonographic (USG) examinations of five enthesal sites of both lower limbs using high-resolution and Doppler USG. An ultrasonographic score of lower limb enthesitis was calculated using Glasgow ultrasound enthesitis scoring system (GUESS). Clinical and laboratory activities of IRD patients were also evaluated. Patient group was made to undergo 2 g/day sulfasalazine monotherapy for 1 year. All evaluations were made at the beginning of the treatment and repeated after 1 year follow-up. Results showed that the frequency of enthesal abnormalities of the IRD group was significantly higher than controls. On USG examination, 301/1,296 (23.2%) enthesal structures were abnormal in IRD patients, and 19/648 (2.93%) structures were abnormal in controls. Mean GUESS score of the IRD group (6.40 +/- 2.41) was also significantly higher than controls (1.79 +/- 1.60) (p < 0.001). Although there was a significant improvement in clinical and laboratory activity parameters of the IRD patients, significant decrease was not observed in enthesal abnormalities (295/1,296 enthesal structures-22.7%) and mean GUESS score (6.20 +/- 2.38) after 1 year sulfasalazine trial. Additionally, there was no significant improvement in enthesal abnormalities and mean GUESS scores of AS and RA subgroups separately. Sulfasalazine treatment was not found effective on enthesal abnormalities of IRD patients. Further studies with
Laria, Antonella; Lurati, Alfredomaria; Marrazza, Mariagrazia; Mazzocchi, Daniela; Re, Katia Angela; Scarpellini, Magda
Macrophages belong to the innate immune system giving us protection against pathogens. However it is known that they are also involved in rheumatic diseases. Activated macrophages have two different phenotypes related to different stimuli: M1 (classically activated) and M2 (alternatively activated). M1 macrophages release high levels of pro-inflammatory cytokines, reactive nitrogen and oxygen intermediates killing microorganisms and tumor cells; while M2 macrophages are involved in resolution of inflammation through phagocytosis of apoptotic neutrophils, reduced production of pro-inflammatory cytokines, and increased synthesis of mediators important in tissue remodeling, angiogenesis, and wound repair. The role of macrophages in the different rheumatic diseases is different according to their M1/M2 macrophages phenotype. PMID:26929657
Klepper, Susan E
The present review discusses the current knowledge about exercise capacity and physical activity in children with rheumatic disease and examines the role of exercise in managing these conditions. Recent studies suggest exercise capacity is significantly impaired in a large proportion of children with juvenile idiopathic arthritis and other rheumatic diseases. These deficits are not limited to children with active inflammation. Children, especially girls, with rheumatoid factor positive polyarticular juvenile idiopathic arthritis, have the greatest deficits. Poor fitness and low levels of weight-bearing physical activity contribute to low bone mass and strength. Children and adolescents with juvenile dermatomyositis and systemic lupus erythematosus also exhibit impaired exercise capacity. There is some evidence that structured aerobic and neuromuscular training may improve exercise capacity, functional performance, and quality of life in children and adolescents with rheumatic disease. A sedentary lifestyle contributes to secondary impairments in aerobic and muscular fitness, bone health, and functional limitations in children and adolescents with rheumatic disease despite advances in the pharmacological management of these inflammatory conditions. Increased levels of moderate to vigorous physical activity and structured exercise may improve exercise capacity, performance of daily activities, and overall quality of life.
Levy, Roger A; de Jesús, Guilherme R; de Jesús, Nilson R; Klumb, Evandro M
The crucial issue for a better pregnancy outcome in women with autoimmune rheumatic diseases is appropriate planning, with counseling of the ideal timing and treatment adaptation. Drugs used to treat rheumatic diseases may interfere with fertility or increase the risk of miscarriages and congenital abnormalities. MTX use post-conception is clearly linked to abortions as well as major birth defects, so it should be stopped 3months before conception. Leflunomide causes abnormalities in animals even in low doses. Although in humans, it does not seem to be as harmful as MTX, when pregnancy is detected in a patient on leflunomide, cholestyramine is given for washout. Sulfasalazine can be used safely and is an option for those patients who were on MTX or leflunomide. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancy centers because of the safety profile and its steroid-sparing property. Cyclosporine and tacrolimus can also be used as steroid-sparing agents, but experience is smaller. Although prednisone and prednisolone are inactivated in the placenta, we try to limit the dose to the minimal effective one, to prevent side effects. Antimalarials have been broadly studied and are safe during pregnancy and breastfeeding. Among biologic disease modifying anti-rheumatic agents (bDMARD), the anti-TNFs that have been used for longer are the ones with greater experience. The large monoclonal antibodies do not cross the placenta in the first trimester, and after conception, the decision to continue medication should be taken individually. The experience is larger in women with inflammatory bowel diseases, where anti-TNF is generally maintained at least until 30weeks to reduce fetal exposure. Live vaccines should not be administrated to the infant in the first 6months of life. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab, ustekinumab, belimumab, and tofacitinib are limited and their use in pregnancy cannot currently be
Shields, Kelly J; Mollnes, Tom Eirik; Eidet, Jon Roger; Mikkelsen, Knut; Almdahl, Sven M; Bottazzi, Barbara; Lyberg, Torstein; Manzi, Susan; Ahearn, Joseph M; Hollan, Ivana
Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA). The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD
Purpose Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. Methods We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. Results IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA). Conclusion The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may
Noninfectious inflammatory diseases (connective tissue diseases, vasculitis syndromes, granulomatous diseases) emerged as the most frequent cause of fever of unknown origin in western countries. Among these diseases, giant cell arteritis and polymyalgia rheumatica are the most frequent specific diagnosis in the elderly and adult-onset Still's disease the most frequent in younger patients. This article focuses on noninfectious inflammatory diseases as a cause of classic fever of unknown origin (mainly rheumatic diseases, such as vasculitis and connective tissue diseases).
This atlas comprises instructive X-rays of the various inflammatory rheumatic joint diseases in all stages at the extremities and the spinal column. In addition, the complex pattern of the wide range of arthroses, also known as degenerative rheumatic disease is included. Besides the instructive pointers to X-ray diagnosis, the book is also a guide to differential diagnosis. Hence, this book is actually an X-ray atlas of joint diseases in general. Selected Contents: Introduction: What Does ''Rheumatism'' Actually Mean./Radiographic Methodology in Rheumatic Diseases of the Locomotor System/The Mosaic of Arthritis/Adult Rheumatoid Arthritis/Seronegative Spondylarthritis/Classic Collagen Diseases/Enthesiopathies/Gout-Pseudogout
Mori, Shunsuke; Hidaka, Michihiro; Kawakita, Toshiro; Hidaka, Toshihiko; Tsuda, Hiroyuki; Yoshitama, Tamami; Migita, Kiyoshi; Ueki, Yukitaka
Objective Severe myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity. Methods We retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups. Results Non-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p < 0.001, p < 0.001, and p = 0.002, respectively). In addition, significantly lower MTX dosages, higher blood cell counts, and lower hemoglobin levels were seen in the myelosuppression group (p < 0.001). No patients exhibited leukocytopenia, neutropenia, or thrombocytopenia in routine blood monitoring taken within the past month. One-fourth developed myelosuppression within the first two months (an early-onset period). Myelosuppression was severe in approximately 40% of patients. Hypoalbuminemia and non-use of folic acid supplements were significantly associated with the severity of pancytopenia (p = 0.001 and 0.008, respectively). Besides these two factors, early onset and the use of lower doses of MTX were significantly associated with the severity of neutropenia (p = 0.003, 0.007, 0.003, and 0.002, respectively). Conclusions Myelosuppression can occur abruptly at any time during low-dose MTX therapy, but severe neutropenia is more likely to occur in the early-onset period of this therapy. Contrary to our expectations, disease severity was not dependent on MTX doses. Serum albumin levels and folic acid
McCoy, Sara S.; Stannard, Jasmine
Activation of the inflammasome, a protein complex responsible for many cellular functions, including the activation of the pro-inflammatory cytokines IL-1β and IL-18, has been identified as a key participant in many rheumatic diseases including autoimmune, inflammatory and autoinflammatory syndromes. This review will discuss the recent advances in understanding the role of this complex in various rheumatic diseases. Further, it will focus on available therapies which directly and indirectly target the inflammasome and its downstream cytokines to quiet inflammation and possibly dampen autoimmune processes. PMID:26118952
Steer, Andrew C; Carapetis, Jonathan R
Acute rheumatic fever and rheumatic heart disease are diseases of socioeconomic disadvantage. These diseases are common in developing countries and in Indigenous populations in industrialized countries. Clinicians who work with Indigenous populations need to maintain a high index of suspicion for the potential diagnosis of acute rheumatic fever, particularly in patients presenting with joint pain. Inexpensive medicines, such as aspirin, are the mainstay of symptomatic treatment of rheumatic fever; however, antiinflammatory treatment has no effect on the long-term rate of progression or severity of chronic valvular disease. The current focus of global efforts at prevention of rheumatic heart disease is on secondary prevention (regular administration of penicillin to prevent recurrent rheumatic fever), although primary prevention (timely treatment of streptococcal pharyngitis to prevent rheumatic fever) is also important in populations in which it is feasible.
Baillet, Athan; Gossec, Laure; Carmona, Loreto; Wit, Maarten de; van Eijk-Hustings, Yvonne; Bertheussen, Heidi; Alison, Kent; Toft, Mette; Kouloumas, Marios; Ferreira, Ricardo J O; Oliver, Susan; Rubbert-Roth, Andrea; van Assen, Sander; Dixon, William G; Finckh, Axel; Zink, Angela; Kremer, Joel; Kvien, Tore K; Nurmohamed, Michael; van der Heijde, Desirée; Dougados, Maxime
In chronic inflammatory rheumatic diseases, comorbidities such as cardiovascular diseases and infections are suboptimally prevented, screened for and managed. The objective of this European League Against Rheumatism (EULAR) initiative was to propose points to consider to collect comorbidities in patients with chronic inflammatory rheumatic diseases. We also aimed to develop a pragmatic reporting form to foster the implementation of the points to consider. In accordance with the EULAR Standardised Operating Procedures, the process comprised (1) a systematic literature review of existing recommendations on reporting, screening for or preventing six selected comorbidities: ischaemic cardiovascular diseases, malignancies, infections, gastrointestinal diseases, osteoporosis and depression and (2) a consensus process involving 21 experts (ie, rheumatologists, patients, health professionals). Recommendations on how to treat the comorbidities were not included in the document as they vary across countries. The literature review retrieved 42 articles, most of which were recommendations for reporting or screening for comorbidities in the general population. The consensus process led to three overarching principles and 15 points to consider, related to the six comorbidities, with three sections: (1) reporting (ie, occurrence of the comorbidity and current treatments); (2) screening for disease (eg, mammography) or for risk factors (eg, smoking) and (3) prevention (eg, vaccination). A reporting form (93 questions) corresponding to a practical application of the points to consider was developed. Using an evidence-based approach followed by expert consensus, this EULAR initiative aims to improve the reporting and prevention of comorbidities in chronic inflammatory rheumatic diseases. Next steps include dissemination and implementation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Raposo, Ana; Peixoto, Daniela; Bogas, Mónica
It is common to find monoclonal gammopathy in the investigation workout for an unrelated disorder. There are studies relating rheumatic diseases and therapies which show an increased risk of monoclonal gammopathy. The specific mechanisms are not well understood but chronic antigen stimulation assumes an important role. Specific rheumatic diseases have consistently been associated with lymphoproliferative disorders but less attention has been paid to the possible association between monoclonal gammopathy of undetermined significance and multiple myeloma. We reviewed previous studies regarding monoclonal gammopathy and different rheumatic diseases and treatments associated focusing on prevalence, risk factors and possible pathogenic mechanisms. The clinical approach of a monoclonal gammopathy and its follow-up are explained.
The Intruduction includes those eflorescences that might be useful for diagnostics in rheumatology. Further in the text we have described four groups of rheumatic disorders. The first group: rheumatic diseases (lupus erythematosus, dermatomyositis, systemic scleroderma, the mixed connective tissue disease, allergic vasculitis, polyarteritis) which are the most common from the dermatological point of view. The second group: rheumatic diseases (Wegener's granulomatosis, rheumatoid arthritis, Sjögren, Reiter and Behçet syndrome and Kawasaki's disease) which are rarely of interest to our dermatologists. In this group there is also psoriatic arthritis, which is not rare in dermatology but its diagnostics and treatment belong to rheumatologists' field of expertise. The third group: infections (rheumatic fever, diseminated gonococcal infection, subacute bacterial endocarditis, Lyme disesease). The fourth group: metabolic disorders (gout). The diseases of the first group are described completely. In the second, third and fourth group of the diseases we have included only skin changes.
Werth, Victoria P; Bashir, Muhammad; Zhang, Wei
There have been a number of recent advances in the genetic understanding of photosensitive rheumatic diseases, especially subacute cutaneous lupus erythematosus and dermatomyositis. These advances support the concept that increased numbers of ultraviolet light-induced apoptotic cells in skin lead to a supra-threshold concentration of antigenic peptides. The current genetic data suggest that increased keratinocyte apopotosis can result from increased amounts of TNF-alpha that induce apoptosis due to a ultraviolet light-sensitive TNF promoter polymorphism or to decreased clearance of apototic cells due to polymorphisms associated with decreased serum levels of collectins such as C1q and mannose-binding lectin. These diseases are frequently oligogenic, and other yet to be elucidated genes will, in individual patients, lead to increased numbers of apoptotic cells associated with these cutaneous autoimmune diseases. In the presence of specific MHC class I and II genes, antigen-presenting cells initiate a primary immune response that leads to cutaneous, and likely systemic, autoimmune disease.
Martinez, Alberto R M; Faber, Ingrid; Nucci, Anamarli; Appenzeller, Simone; França, Marcondes C
Systemic manifestations are frequent in autoimmune rheumatic diseases and include peripheral nervous system damage. Neuron cell body, axons and myelin sheath may all be affected in this context. This involvement results in severe and sometimes disabling symptoms. Sensory, motor and autonomic features may be present in different patterns that emerge as peculiar clinical pictures. Prompt recognition of these neuropathies is pivotal to guide treatment and reduce the risks of long term disability. In this review, we aim to describe the main immune-mediated neuropathies associated to rheumatic diseases: sensory neuronopathies, multiple mononeuropathies and chronic inflammatory demyelinating polyradiculoneuropathy, with an emphasis on clinical features and therapeutic options.
Matuszewska, Genowefa; Zaniewicz-Kaniewska, Katarzyna; Włodkowska-Korytkowska, Monika; Smorawińska, Patrycja; Saied, Fadhil; Kunisz, Wojciech; Sudoł-Szopińska, Iwona
Summary Radiological imaging plays a fundamental role in the diagnosis and monitoring of rheumatic diseases. The basic method of imaging is a classic X-ray picture, which for many years has been used as a single method for the recognition and evaluation of the effects of disease management. In today’s modern day treatment of rheumatic diseases, ultrasonography and magnetic resonance are more commonly performed for early detection of inflammatory changes in the region of soft tissue, subchondral bone and bone marrow. In spite of their usefulness and fundamental role in the diagnosis, X-ray still remains an essential tool in the diagnosis of rheumatoid arthritis in children and is complementary to today’s methods of imaging diagnostics. In clinical practice, X-ray imaging is still an important examination performed not only to recognize the disorders, but also to provide a differential diagnosis. It helps estimate disease progression and is used to monitor the effects of treatment and the development of possible complications. Differential diagnosis of rheumatic diseases is performed on the basis of localization and type of radiographic changes. The surrounding periarticular soft tissues, bone structures, joint space, with special attention to articular bone surfaces and epiphyses, are analyzed. The aim of this work is to describe characteristic inflammatory changes present on X-ray imaging typical for the most commonly diagnosed rheumatic diseases in children, such as juvenile idiopathic arthritis, systemic lupus erythematosus, systemic scleroderma, mixed connective tissue disease, juvenile dermatomyositis, juvenile spondyloarthropathy and systemic vascular disease. PMID:24669280
Driazhenko, I V
Cardiovascular system involvement with early development of atherosclerosis is characteristic for rheumatic diseases. Among causes of death in various rheumatic diseases cardiovascular pathology also prevails. This paper contains a review of most important studies of impairment of the heart, arterial and venous parts of cardiovascular system in patients with diffuse diseases of connective tissue, rheumatoid arthritis and systemic vasculitides. The role of immune mechanisms, endothelial dysfunction, dyslipidemia in pathogenesis of cardiovascular disturbances with development of myocardial and vascular remodeling in rheumatic diseases is also discussed. Major risk factors of cardiovascular pathology in rheumatic patients are presented. Treatment of a cardiovascular pathology in these patients presumes the use of angiotensin converting enzyme inhibitors, aldosterone antagonists and statins.
Prasad, Megha; Hermann, Joerg; Gabriel, Sherine E.; Weyand, Cornelia M.; Mulvagh, Sharon; Mankad, Rekha; Oh, Jae K.; Matteson, Eric L.; Lerman, Amir
Autoimmune rheumatic diseases can affect the cardiac vasculature, valves, myocardium, pericardium, and conduction system, leading to a plethora of cardiovascular manifestations that can remain clinically silent or lead to substantial cardiovascular morbidity and mortality. Although the high risk of cardiovascular pathology in patients with autoimmune inflammatory rheumatological diseases is not owing to atherosclerosis alone, this particular condition contributes substantially to cardiovascular morbidity and mortality—the degree of coronary atherosclerosis observed in patients with rheumatic diseases can be as accelerated, diffuse, and extensive as in patients with diabetes mellitus. The high risk of atherosclerosis is not solely attributable to traditional cardiovascular risk factors: dysfunctional immune responses, a hallmark of patients with rheumatic disorders, are thought to cause chronic tissue-destructive inflammation. Prompt recognition of cardiovascular abnormalities is needed for timely and appropriate management, and aggressive control of traditional risk factors remains imperative in patients with rheumatic diseases. Moreover, therapies directed towards inflammatory process are crucial to reduce cardiovascular disease morbidity and mortality. In this Review, we examine the multiple cardiovascular manifestations in patients with rheumatological disorders, their underlying pathophysiology, and available management strategies, with particular emphasis on the vascular aspects of the emerging field of ‘cardiorheumatology’. PMID:25533796
Villar-Hernández, Raquel; Latorre, Irene; Mínguez, Sonia; Díaz, Jéssica; García-García, Esther; Muriel-Moreno, Beatriz; Lacoma, Alicia; Prat, Cristina; Olivé, Alex; Ruhwald, Morten; Mateo, Lourdes; Domínguez, José
Biologic agents are used against rheumatic diseases, however, they increase the risk of developing severe infections and diseases such as tuberculosis. We aimed to determine the benefits of IP-10 detection to diagnose latent tuberculosis infection (LTBI) in patients with inflammatory rheumatic diseases on different immunosuppressive drug regimens, and compare these results with IFN-γ detection. We included 64 patients with inflammatory rheumatic diseases. We used QuantiFERON Gold In-Tube (QFN-G-IT) and T-SPOT.TB to detect IFN-γ production, and an in-house ELISA for IP-10 detection from the previous QFN-G-IT stimulated samples. We assessed the combined use of IFN-γ release assays (IGRAs) and IP-10 test, and analyzed the influence of immunotherapy on the tests performance. We obtained 34.9% positive results by T-SPOT.TB, 25.0% by QFN-G-IT and 31.3% by IP-10 test. The combined use of IGRAs and IP-10 detection increased significantly the amount of positive results (p < 0.0001). Treatment intake had no significant effect on in vitro tests (p > 0.05). IP-10 and IFN-γ detection is comparable and their combined use could increase the number of positive results in the diagnosis of LTBI in rheumatic patients. The tested assays were not influenced by rheumatoid immunosuppressive therapy. Thus, IP-10 could be of use in the development of new and improved LTBI diagnostic tools. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
The use of IVIG to treat a wide variety of immune-driven diseases has grown rapidly, although the mechanism of action is not completely understood. Increasing demand for IVIG coupled with concerns regarding potential transmissible agents has led to worldwide supply shortages. National agencies have therefore produced guidelines for its use, with the latest England and Wales guideline being published in 2011. Due to the rarity of the rheumatic diseases, the evidence for IVIG use has been shown to be lacking in some areas and promising in others. Conditions in which IVIG has been shown to have benefit include ITP, Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy occurring in the context of rheumatic disease, as well as in SLE, idiopathic inflammatory myopathies and ANCA-associated vasculitides. This review looks at current IVIG use and is designed to be an aid for rheumatologists when considering the use of IVIG in clinical practice. PMID:25406359
Fatigue is a common symptom in a large number of medical and psychological disorders, including many rheumatologic illnesses. A frequent question for health care providers is related to whether reported fatigue is "in the mind" or "in the body"-that is, central or peripheral. If fatigue occurs at rest without any exertion, this suggests psychological or central origins. If patients relate their fatigue mostly to physical activities, including exercise, their symptoms can be considered peripheral. However, most syndromes of fatigue seem to depend on both peripheral and central mechanisms. Sometimes, muscle biopsy with histochemistry may be necessary for the appropriate tissue diagnosis, whereas serological tests generally provide little reliable information about the origin of muscle fatigue. Muscle function and peripheral fatigue can be quantified by contractile force and action potential measurements, whereas validated questionnaires are frequently used for assessment of mental fatigue. Fatigue is a hallmark of many rheumatologic conditions, including fibromyalgia, myalgic encephalitis/chronic fatigue syndrome, rheumatoid arthritis, systemic lupus, Sjogren's syndrome, and ankylosing spondylitis. Whereas many studies have focused on disease activity as a correlate to these patients' fatigue, it has become apparent that other factors, including negative affect and pain, are some of the most powerful predictors for fatigue. Conversely, sleep problems, including insomnia, seem to be less important for fatigue. There are several effective treatment strategies available for fatigued patients with rheumatologic disorders, including pharmacological and nonpharmacological therapies.
Anić, Branimir; Cikes, Nada
The specific pharmacotherapy in pregnant women is of great importance in chronic inflammatory rheumatic diseases. Before every potential pregnancy or afterwards the knowledge of pregnancy of women with inflammatory rheumatic disease, it is necessary to evaluate the pregnancy risk for patient and child. The purpose of this review is to give concise informations about the most frequent used drugs in rheumatology and their use in pregnancy and lactation.
Soy, Mehmet; Guldiken, Sibel; Arikan, Ender; Altun, Betul Ugur; Tugrul, Armagan
We aimed to investigate the frequency of rheumatic diseases in patients suffering from autoimmune thyroid diseases (ATD). Sixty-five patients (56 F, 9 M), who were followed by diagnosis of ATD, were questioned and examined for the presence of rheumatic disease. Basic laboratory tests and antithyroid antibodies, antinuclear antibody and rheumatoid factor (RF) levels were also measured by appropriate methods. Various rheumatic diseases were detected in 40 (62%) of patients with ATD. The most frequent rheumatic conditions were fibromyalgia, recurrent aphthous stomatitis, osteoarthritis, keratoconjunctivitis sicca and xerostomia and carpal tunnel syndrome which were detected in 20 (31%), 13 (20%), 10 (15%), 9 (14%) and 8 (12%) of patients, respectively. Autoimmune diseases, except Sjogren's syndrome, which were detected in ten patients with ATD, are as follows-vitiligo: two; autoimmune hepatitis: two; oral lichen planus: one, ulcerative colitis: one, inflammatory arthritis in four patients (two of them had rheumatoid arthritis, one had psoriasis and psoriatic arthritis and one had mixed collagen tissue disease). RF was positive in two patients, one of them had rheumatoid arthritis and FANA was positive in six (9%) patients; all of them had hypothyroidism. The frequency of rheumatic diseases seems to be higher in patients suffering from ATD. Initial evaluation and a regular checking for rheumatic diseases in patients suffering from ATD were recommended.
Saxena, Anita; Kumar, R Krishna; Gera, Rani Prem Kumar; Radhakrishnan, S; Mishra, Smita; Ahmed, Z
Acute rheumatic fever and rheumatic chronic valvular heart disease is an important preventable cause of morbidity and mortality in suburban and rural India. Its diagnosis is based on clinical criteria. These criteria need verification and revision in the Indian context. Furthermore, there are glaring differences in management protocols available in literature. These facts prompted Indian Academy of Pediatrics to review the management of rheumatic fever. Management of Rheumatic fever was reviewed and recommendation was formulated at national consultative meeting on 20th May 2007 at New Delhi. To formulate uniform guidelines on management of acute rheumatic fever and rheumatic heart disease in the Indian context. Guidelines were formulated for the management of streptococcal pharyngitis, acute rheumatic fever and its cardiac complication as well as secondary prophylaxis for recurrent episodes. (1) Streptococcal eradication with appropriate antibiotics (Benzathine penicillin single dose or penicillin V oral or azithromycin). (2) Diagnosis of rheumatic fever based on Jones criteria. (3) Control inflammatory process with aspirin with or without steroids (total duration of treatment of 12 weeks). (4) Treatment of chorea according to severity (therapy to continue for 2-3 weeks after clinical improvement). (5) Protocol for managing cardiac complication like valvular heart disease, congestive heart failure and atrial fibrillation. (6) Secondary prophylaxis with benzathine penicillin and management of anaphylaxis.
Mérot, O; Le Goff, B
Musculoskeletal ultrasonography is now widely used by almost all rheumatologists thanks to an improvement in the quality of ultrasound unit and probe and to the systematic teaching of this imaging technique to the rheumatology fellows. Applications have broadened from the study of degenerative and mechanical diseases to inflammatory rheumatic diseases. Ultrasound is more sensitive than clinical examination. Power Doppler allows the direct visualisation of inflammation within the tissues. Finally, it is a prognostic tool helping the physician in the management of the disease. This review will focus on the value and applications of ultrasonography in the 2 most frequent rheumatic diseases: rheumatoid arthritis and spondyloarthritis. We will also give some recent data on the usefulness of this imaging technique in the study of musculoskeletal manifestations associated with connective tissue disease.
Żbikowski, Piotr; Kwiatkowska, Brygida; Buscombe, John R.; Sudoł-Szopińska, Iwona
Radiosynovectomy is a safe and repeatable treatment method of chronic synovitis with synovial overgrowth and refractory chronic or acute inflammatory joint effusion. It consist in the intraarticular administration of a radioactive isotope in the form of a colloid causing the extinguishing of active synovitis. The radiocolloid causes permanent irradiation of the synovium with beta ray electron beams, which ultimately leads to its fibrosis and extinguishes the inflammatory process destroying the joint. The main indications for radiosynovectomy include chronic and acute arthritis in the course of systemic diseases, intraarticular bleeding in hemorrhagic diatheses (hemophilia), selected cases of osteoarthritis, recurrent effusions following surgery, e.g. arthroplasty, or other iatrogenic post-surgery complications causing arthritis. Radiosynovectomy is also performed in pigmented villonodular synovitis and crystal synovitis. The most common method used to determine the eligibility for radiosynovectomy is an ultrasound, which shows the location and activity of the thickened synovium. The administration of a radiocolloid into the joint, sheath or bursa should also be performed under the control of the ultrasound image, as this ensures a precise location of the puncture needle and full control of the isotope administration process. Clinical efficacy of radiosynovectomy depends on the proper qualification of patients for the procedure. The success rate of radiosynovectomy in common indications is 65–80%. It is confirmed by the visualization of avascular (fibrotic) synovium in follow-up ultrasound tests. The aim of this article is to present techniques and indications for the radiosynovectomy treatment. PMID:26673861
Falsetti, Paolo; Acciai, Caterina; Lenzi, Lucia; Frediani, Bruno
Enthesopathy is the pathologic change of the insertion of tendons, ligaments and joint capsules on the bone. It is a cardinal feature of spondyloarthropathies (SpA), but it can occur in other rheumatic disease. Recent studies using magnetic resonance imaging (MRI) and ultrasonography (US) have demonstrated that enthesopathy can often be asymptomatic, in both the axial and peripheral skeleton. Therefore, a systematic US study of peripheral entheses could be useful in the diagnostic process of patients with rheumatic diseases, in particular SpA. Recently, power Doppler US (PDUS) has been proved to be useful for differentiating mechanical/degenerative and inflammatory enthesopathy and for monitoring the efficacy of therapy. This article reviews the main histopathologic aspects of enthesopathy and describes the normal US features of enthesis and the basic US features of enthesopathy, in its various stages. The usefulness of US and PDUS in the diagnosis and assessment of enthesopathy is discussed on the basis of the literature and our experience.
Van de Wiele, Tom; Van Praet, Jens T; Marzorati, Massimo; Drennan, Michael B; Elewaut, Dirk
The human gut harbours a tremendously diverse and abundant microbial community that correlates with, and even modulates, many health-related processes. The mucosal interfaces are particularly active sites of microorganism-host interplay. Growing insight into the characteristic composition and functionality of the mucosal microbiota has revealed that the microbiota is involved in mucosal barrier integrity and immune function. This involvement affects proinflammatory and anti-inflammatory processes not only at the epithelial level, but also at remote sites such as the joints. Here, we review the role of the gut microbiota in shaping local and systemic immune responses and how disturbances in the host-microorganism interplay can potentially affect the development and progression of rheumatic diseases. Increasing our understanding of how to promote host-microorganism homeostasis could therefore reveal novel strategies for the prevention or alleviation of rheumatic disease.
Sangle, Shirish R; Tench, Colin M; D'Cruz, David P
Sleep has an important role to play in the human immune system and it is critical in the restoration and maintenance of homeostasis. Sleep deprivation and disorders may have a profound impact on health, well being and the ability to resist infection. Autoimmune rheumatic diseases are multisystem disorders that involve complicated hormonal and immunological pathophysiology. Previous studies have suggested that sleep deprivation may lead to immunological disturbance in experimental mouse models. Sleep disorders may trigger immune system abnormalities inducing autoantibody production, possibly leading to the development of autoimmune disease such as systemic lupus erythematosus, scleroderma or rheumatoid arthritis. Indeed, in experimental models, it has been suggested that sleep deprivation may induce the onset of autoimmune disease. Chronic deprivation of sleep is common in modern society and has been seen in various autoimmune inflammatory rheumatic diseases. We have reviewed various aspects of sleep deprivation and sleep apnoea syndrome, and their effects on the immune system and their relevance to autoimmune diseases. We hope that these data will encourage greater awareness of the role that improved sleep hygiene may play in the management of these rheumatic diseases.
Klauser, Andrea Sabine
Ultrasound (US) is a useful tool in the assessment of rheumatic disease. It permits assessment of early erosive changes and vascularity detection in synovial proliferation, caused by inflammatory activity by using colour/power Doppler US (CDUS/PDUS). In the detection of slow flow and flow in small vessels, the CDUS/PDUS technique is limited. Contrast enhanced US can improve the detection of inflammatory vascularity but is not yet included in routine diagnosis of this condition. However, contrast enhanced US shows promising results in diagnosis, assessment of disease activity and follow up of inflammatory rheumatic diseases.
Steroid hormones are deeply involved in the pathophysiology of immune-mediated rheumatic diseases and used for their treatment. Purpose of the review is to update on recent roles and mechanisms of action of important steroid hormones such as glucocorticoids, estrogens, and D hormone (vitamin D) in order to optimize their therapeutical use. Endogenous glucocorticoids are characterized by a circadian rhythm of production that must be respected in case of exogenous low-dose long-term glucocorticoid replacement therapy of rheumatic diseases. Estrogens are enhancers of the humoral immune response and increase cell proliferation. Therefore, estrogens represent a risk factor for the development of autoimmunity and their therapeutical use must be avoided in patients with active immune-mediated diseases. Vitamin D, as synthesized in the skin from cholesterol, is a real steroid hormone (D hormone). The immunosuppressive activities of D hormone are reduced in chronic rheumatic diseases, as low plasma levels of the hormone are evident and justify its therapeutical use. The optimization of the therapeutical use of steroid hormones such as glucocorticoids, estrogens or D hormone is now possible following recent basic and clinical research achievements.
Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: study using the Spanish registry of adverse events of biological therapies in rheumatic diseases.
Hernández, M Victoria; Sanmartí, Raimon; Cañete, Juan D; Descalzo, Miguel A; Alsina, Mercè; Carmona, Loreto; Gomez-Reino, Juan J
To analyze the incidence rate (IR) and risk factors of cutaneous adverse events (CAE) in patients with chronic inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) antagonists. We analyzed all patients from the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) registry treated with a TNF antagonist (infliximab, etanercept, or adalimumab). Data collected included age, sex, diagnosis and duration of rheumatic disease, type of TNF antagonist, and concomitant treatment. Type of CAE was classified as local or systemic cutaneous manifestation related to treatment administration (infusion reaction), infection, malignancy, or autoimmune skin disease. Time of onset of CAE and outcome were also recorded. The IRs of CAE per 1,000 patient-years of exposure with 95% confidence intervals (95% CIs) were estimated. Multivariable analysis was performed to identify potential risk factors for CAE. A total of 5,437 patients were included, representing 17,330 patient-years of exposure. A total of 920 CAE were reported; the IRs per 1,000 patient-years were 53 (95% CI 50-57) for CAE, 28 (95% CI 25-30) for infection, 15 (95% CI 13-17) for infusion reactions, 5 (95% CI 4-6) for autoimmune skin diseases, and 3 (95% CI 2-4) for skin malignancy. The mean time between starting TNF antagonist treatment and CAE was 1.78 years. In 32% of patients, CAE required TNF antagonist withdrawal. The main risk factors for CAE were female sex and treatment with infliximab, leflunomide, and glucocorticoids. The IR of CAE in patients treated with TNF antagonists is significant and should be addressed carefully, and withdrawal of therapy is required in some cases. Copyright © 2013 by the American College of Rheumatology.
Background Pediatric rheumatic diseases have a significant impact on children’s quality of life and family functioning. Disease control and management of the symptoms are important to minimize disability and pain. Specialist clinical nurses play a key role in supporting medical teams, recognizing poor disease control and the need for treatment changes, providing a resource to patients on treatment options and access to additional support and advice, and identifying best practices to achieve optimal outcomes for patients and their families. This highlights the importance of investigating follow-up telenursing (TN) consultations with experienced, specialist clinical nurses in rheumatology to provide this support to children and their families. Methods/Design This randomized crossover, experimental longitudinal study will compare the effects of standard care against a novel telenursing consultation on children’s and family outcomes. It will examine children below 16 years old, recently diagnosed with inflammatory rheumatic diseases, who attend the pediatric rheumatology outpatient clinic of a tertiary referral hospital in western Switzerland, and one of their parents. The telenursing consultation, at least once a month, by a qualified, experienced, specialist nurse in pediatric rheumatology will consist of providing affective support, health information, and aid to decision-making. Cox’s Interaction Model of Client Health Behavior serves as the theoretical framework for this study. The primary outcome measure is satisfaction and this will be assessed using mixed methods (quantitative and qualitative data). Secondary outcome measures include disease activity, quality of life, adherence to treatment, use of the telenursing service, and cost. We plan to enroll 56 children. Discussion The telenursing consultation is designed to support parents and children/adolescents during the course of the disease with regular follow-up. This project is novel because it is based
... treatment strategies in the future. The clustering of multiple and different autoimmune diseases is observed frequently in ... diseases are caused by a complicated interaction of multiple genes and environmental factors such as age, gender, ...
Murdaca, Giuseppe; Colombo, Barbara Maria; Cagnati, Paola; Gulli, Rossella; Spanò, Francesca; Puppo, Francesco
Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, β2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities
Jüngel, A; Gay, S
The human genome comprises approximately 30000 genes needed for the formation and function of approximately 1 Million proteins in the human body. Differentiation leads to the deactivation of genes that are not needed in the specific tissues or cells. To regulate the cell specific gene expression in normal cells epigenetic modifications work in concert with genetic mechanisms. In contrast to genetic mutations, epigenetics encompasses the wide range of heritable changes in gene expression that do not result from alteration in the DNA sequence itself. A dysregulation of epigenetic modifications results in diseases such as cancer or autoimmune diseases. Since these epigenetic modifications of the DNA and the histones are reversible they are good targets for novel therapeutic intervention.
Jager, Nynke A; Teteloshvili, Nato; Zeebregts, Clark J; Westra, Johanna; Bijl, Marc
In patients with systemic auto-immune inflammatory rheumatic diseases (AIIRD) like rheumatoid arthritis the prevalence of cardiovascular disease (CVD) is increased. In the pathogenesis of AIIRD and atherosclerosis many similarities can be found in the process underlying CVD. Accumulation of inflammatory cells, in particular macrophages at the site of inflammation producing inflammatory mediators serve as a prominent feature in both systemic inflammation and atherosclerosis. Two different subtypes of macrophages have been described in recent literature namely classically activated macrophages (M1) and alternatively activated macrophages (M2). Alternatively activated macrophages are characterized by low CD14 and high CD163 expression. Macrophages expressing CD14 (M1) have been identified within atherosclerotic plaques, whereas CD14 low macrophages are abundant in vessels without atherosclerosis. Depending on the environment and responses to different stimuli, macrophages in plaques can express diverse pro and anti-atherogenic functions. The balance of these different activation profiles influences atheroma evolution and outcome. Nowadays, influx of macrophages is recognized as a very important feature of the pathogenesis of plaque formation. Activated macrophages accumulate at the sites of inflammation and can therefore be exploited to better visualize inflammatory responses in atherosclerosis. Furthermore, activated (but not resting) macrophages possess a functionally active receptor for folate (FR-β), but it is not completely clear which subtype of this activated macrophages expresses this receptor and whether the expression of FR-β is restricted to only one of the macrophage subsets. Although future research needs to be done to investigate FR-β expression and function within inflamed tissues, the expression of functional FR-β on tissue macrophages likely occurs during activation. Therefore, expression of FR-β on activated macrophages holds a promising
Kłak, Anna; Raciborski, Filip; Samel-Kowalik, Piotr
Social consequences of a disease constitute limitations in performing roles relating to working life as well as family and social life caused by the disease, mainly chronic. The aim of the study was to analyze the social consequences of rheumatic diseases in the aspect of disability pensions with respect to incapacity for work and quality of life. The occurrence of rheumatic diseases is related not only to increased risk of different types of organic changes, but above all disability. In Europe almost 50% of persons suffering from diseases of the musculoskeletal system who are currently unemployed were breadwinners. Nearly 60% of them received legal disability status. The loss of work ability is, among other things, the consequence of progressive disability. In Europe 40% of persons suffering from rheumatoid arthritis (RA) had to stop working due to the disease. Most of the persons diagnosed with RA were of working age. It results in the decrease in the quality of life as well as economic difficulties (decreased incomes and increased disease-related costs). In Poland the results of the analysis of the Social Insurance Institution (ZUS) of first-time disability recognition issued for the purpose of disability pensions in 2014 showed that the incapacity for work was caused by diseases relating to general health condition (65.5%). Diseases of the musculoskeletal system were the cause of partial inability to work of 21.6% of persons who received a disability pension for the first time (as many as 5,349 certificates were issued). Early diagnosis and implementation of effective treatment are the necessary conditions for a patient to sustain activity, both professional and social, which is of crucial importance to reduce the negative effects of the disease.
Rao, Jaya K; Hootman, Jennifer M
Prevention may occur in clinical, community, or population settings and is often classified into primary, secondary, and tertiary types. To provide a context for this review, we define the three types and provide general and arthritis-specific examples of prevention strategies. Next, we highlight recently published longitudinal cohort and intervention studies that focus on arthritis prevention in the following topic areas: cognitive and behavioral strategies, obesity, exercise, and occupational injury prevention. Few studies examined primary prevention strategies. In one study, an educational intervention significantly changed tick-related knowledge and behaviors among a population at risk of Lyme disease. Another population-based study used a mailed, stage-based educational program to successfully increase physical activity levels; this intervention may have practical application as a primary or tertiary prevention strategy for arthritis. Tertiary prevention research received much attention: Recent studies extend the benefits of exercise and cognitive-behavioral interventions to persons with different rheumatic conditions (eg, neck pain, low back pain, systemic lupus erythematosus, fibromyalgia). Longitudinal cohort studies improve our understanding of the relationships between computer use and carpal tunnel syndrome among office workers, birth weight and hand osteoarthritis, and baseline balance and functional declines among older adults with knee pain. Prevention of arthritis and its complications is an active focus of investigation. Primary prevention research remains a challenge because of the prolonged time frame for disease expression. Scientific evidence continues to provide support for tertiary prevention strategies among people with documented rheumatic disease.
Aceves-Avila, F J; Fraga, A
The medical texts published in New Spain between the XVI and XVIII century have not been searched until now for evidence of the existence of rheumatoid arthritis and other rheumatic diseases before the descriptions made by Sydenham. We surveyed most of the medical books written and published in New Spain from the arrival of the Spaniards to the XVIII century, and we divided the diseases with articular manifestations into four groups, according to their main clinical characteristics: pain without swelling in anatomical region; pain without swelling in several joints; pain and swelling in joints, and joint complaints associated with contagious diseases. We found that a difference was established between gout and rheumatoid arthritis one hundred years before Sydenham, according to the different evolutions of both diseases, and we present one of the oldest descriptions of reactive arthritis.
Galloway, James; Cope, Andrew P
Fevers are relatively common in rheumatic disease, largely due to the fact that the inflammatory process is driven by inflammatory mediators that function as endogenous pyrogens. Since the immune system's sensors cannot accurately distinguish between endogenous and exogenous (pathogen-derived) pyrogens a major challenge for physicians and rheumatologists has been to decipher patterns of clinical signs and symptoms to inform clinical decision making. Here we describe some of the common pitfalls and clinical challenges, and highlight the importance of a systematic approach to investigating the rheumatic disease patient presenting with fever.
Mirror therapy reduces chronic pain and might also be suitable for the treatment of inflammatory rheumatic pain. On the basis of the relevant literature this article a) characterizes the universal alterations in body perception and body representation in chronic pain, b) describes the potential mechanisms underlying mirror therapy and c) discusses the chances of success of mirror therapy for the treatment of inflammatory rheumatic pain. Literature search on the effectiveness and mechanisms of mirror therapy and derived procedures for the potential treatment of pain in inflammatory rheumatic disorders. There is evidence that mirror therapy can alleviate chronic pain experiences by correcting the accompanying distorted body perception as well as body representation by multimodal sensory stimulation. As there is probably a similar distortion in persons with chronic pain related to inflammatory rheumatic disorders, mirror therapy might also have positive effects in this field; however, the accompanying characteristics of these disorders, such as motor impairment and motor-evoked pain, may complicate the implementation of this kind of treatment. Mirror therapy represents an intervention with few side effects and might have positive effects on the experience of chronic pain in patients with inflammatory rheumatic disorders. Further clinical research is required in order to evaluate the potential of mirror therapy and associated interventional methods for the treatment of inflammatory rheumatic pain.
Widuchowska, Małgorzata; Kucharz, Eugeniusz J.
Calprotectin also known as MRP8/14 or S100A8/A9 is a heterodimeric complex of two S100 calcium-binding proteins: myeloid-related protein 8 (MRP-8 or S100A8) and MRP-14 (or S100A9). At present, according to many authors, it is considered that calprotectin MRP8/14 is a potentially more sensitive biomarker of disease activity in rheumatoid disease than conventional inflammatory indices such as the erythrocyte sedimentation rate, C-reactive protein and others. A review of the literature on concentration of calprotectin in patients with some rheumatic diseases (rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still’s disease, systemic vasculitis, polymyalgia rheumatica, ankylosis spondylitis, systemic lupus erythematosus, and primary Sjögren’s syndrome) is presented. PMID:28115781
Kopeć-Mędrek, Magdalena; Widuchowska, Małgorzata; Kucharz, Eugeniusz J
Calprotectin also known as MRP8/14 or S100A8/A9 is a heterodimeric complex of two S100 calcium-binding proteins: myeloid-related protein 8 (MRP-8 or S100A8) and MRP-14 (or S100A9). At present, according to many authors, it is considered that calprotectin MRP8/14 is a potentially more sensitive biomarker of disease activity in rheumatoid disease than conventional inflammatory indices such as the erythrocyte sedimentation rate, C-reactive protein and others. A review of the literature on concentration of calprotectin in patients with some rheumatic diseases (rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, systemic vasculitis, polymyalgia rheumatica, ankylosis spondylitis, systemic lupus erythematosus, and primary Sjögren's syndrome) is presented.
This book is an ''atlas of rheumatic joint disease'' selected from 20 years of personal experience by the author. The author sets a goal of demonstrating the value of soft-tissue imaging in the diagnosis of early joint disease. This goal is achieved with high quality reproductions, many of which are presented in duplicate to illustrate bone and soft-tissue changes. The contents include an introductory overview of the ''Mosaic of Arthritis'' followed by sections on adult rheumatoid arthritis, seronegative spondyloarthropathies, classic collagen disease, enthesiopathies, and lastly a section on gout and psuedogout. The subject index is specific and indexes figures with boldface type. Each section is introduced by a brief outline or overview of the radiographic spectrum of the joint disorder to be illustrated.
Straub, R H; Fassold, A
Clinical observations in chronic inflammatory diseases have demonstrated the significant influence of neuroendocrine mechanisms on the immune system: (1) Amelioration of rheumatoid arthritis during pregnancy; (2) preponderance of women versus men with respect to autoimmune diseases; (3) negative effects of ovulation-inducing therapy, oral contraceptives, and hormone replacement therapy; (4) protective effect of hemiplegia; (5) influence of psychological stress on inflammation; and (6) influence of circadian rhythms on inflammatory symptoms.The effects of different hormones and neurotransmitters on the immune system are influenced by: (1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses, (2) the cell types involved during different phases of the disease, (3) the target organ with its specific microenvironment, (4) the timing of hormone or neurotransmitter increase in relation to the disease course, (5) the concentration of hormones and neurotransmitters, (6) the variability in expression of receptors depending on the microenvironment and the cell type, and (7) the intra- and extracellular peripheral metabolism of hormones and neurotransmitters leading to important biologically active metabolites with quite different anti- and proinflammatory functions.The circadian rhythm of disease-related symptoms with a peak in the early morning hours confirms that the neuroendocrine system has a strong influence on these chronic immune/inflammatory diseases. The influence is transmitted by the circadian fluctuation in the activity of hormonal and neuronal pathways linking the brain to immune cell activation.These considerations could lead to novel therapeutic strategies for rheumatic diseases in the future.
Zhang, Yujuan; Milojevic, Diana
Bone health in children with rheumatic conditions may be compromised due to several factors related to the inflammatory disease state, delayed puberty, altered life style, including decreased physical activities, sun avoidance, suboptimal calcium and vitamin D intake, and medical treatments, mainly glucocorticoids and possibly some disease-modifying anti-rheumatic drugs. Low bone density or even fragility fractures could be asymptomatic; therefore, children with diseases of high inflammatory load, such as systemic onset juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, and those requiring chronic glucocorticoids may benefit from routine screening of bone health. Most commonly used assessment tools are laboratory testing including serum 25-OH-vitamin D measurement and bone mineral density measurement by a variety of methods, dual-energy X-ray absorptiometry as the most widely used. Early disease control, use of steroid-sparing medications such as disease-modifying anti-rheumatic drugs and biologics, supplemental vitamin D and calcium, and promotion of weight-bearing physical activities can help optimize bone health. Additional treatment options for osteoporosis such as bisphosphonates are still controversial in children with chronic rheumatic diseases, especially those with decreased bone density without fragility fractures. This article reviews common risk factors leading to compromised bone health in children with chronic rheumatic diseases and discusses the general approach to prevention and treatment of bone fragility.
SYNOPSIS Many patients with chronic rheumatic diseases such as osteoarthritis, rheumatoid arthritis and fibromyalgia experience high levels of pain, psychological distress and negative emotions and have limited therapeutic options. Tai Chi is a complex multi-component mind-body exercise that increasing numbers of Americans are practicing, particularly those with musculoskeletal conditions. Clinical trials and observational studies have provided encouraging evidence that Tai Chi, both short and long-term, has benefits for patients with a variety of chronic disorders. As a form of physical exercise, Tai Chi enhances cardiovascular fitness, muscular strength, balance, and physical function. It also appears to be associated with reduced stress, anxiety and depression as well as improved quality of life. Thus, despite the noted limitations in the evidence, and the need for further methodologically rigorous studies, Tai Chi can be safely recommended to patients with osteoarthritis, rheumatoid arthritis and fibromyalgia as a complementary and alternative medical approach to affect patient well-being. This overview synthesizes the current body of knowledge about this ancient Chinese mind-body medicine to better inform clinical decision-making for our rheumatic patients. PMID:21220083
Islam, A K M Monwarul; Majumder, A A S
Rheumatic fever (RF) and rheumatic heart disease (RHD) are the most-common cardiovascular disease in young people aged <25 years, globally. They are important contributors to cardiovascular morbidity and mortality in Bangladesh. Classical risk factors, i.e. poverty, overcrowding, ignorance, and insufficient health care services were responsible for the high incidence and prevalence of these diseases over the last century. In concert with the progresses in socioeconomic indicators, advances in health sectors, improved public awareness, and antibiotic prophylaxis, acute RF came into control. However, chronic RHD continues to be prevalent, and the actual disease burden may be much higher. RHD predominantly affects the young adults, seriously incapacitates them, follows a protracted course, gets complicated because of delayed diagnosis and is sometimes maltreated. The treatment is often palliative and expensive. Large-scale epidemiological and clinical researches are needed to formulate evidence-based national policy to tackle this important public health issue in future.
Islam, A.K.M. Monwarul; Majumder, A.A.S.
Rheumatic fever (RF) and rheumatic heart disease (RHD) are the most-common cardiovascular disease in young people aged <25 years, globally. They are important contributors to cardiovascular morbidity and mortality in Bangladesh. Classical risk factors, i.e. poverty, overcrowding, ignorance, and insufficient health care services were responsible for the high incidence and prevalence of these diseases over the last century. In concert with the progresses in socioeconomic indicators, advances in health sectors, improved public awareness, and antibiotic prophylaxis, acute RF came into control. However, chronic RHD continues to be prevalent, and the actual disease burden may be much higher. RHD predominantly affects the young adults, seriously incapacitates them, follows a protracted course, gets complicated because of delayed diagnosis and is sometimes maltreated. The treatment is often palliative and expensive. Large-scale epidemiological and clinical researches are needed to formulate evidence-based national policy to tackle this important public health issue in future. PMID:26896274
Ramos, Paula S
Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Natural selection is an important influence on human genetic variation. Because immune and inflammatory function genes are enriched for signals of positive selection, the prevalence of rheumatic disease-risk alleles seen in different populations is partially the result of differing selective pressures (eg, due to pathogens). This review summarizes the genetic regions associated with susceptibility to different rheumatic diseases and concomitant evidence for natural selection, including known agents of selection exerting selective pressure in these regions. Copyright © 2017 Elsevier Inc. All rights reserved.
Ostensen, M; Forger, F; Nelson, J; Schuhmacher, A; Hebisch, G; Villiger, P
Objective: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). Methods: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon γ (IFNγ), interleukin (IL) 1ß, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines. Results: Low levels of IL10 were found sporadically, whereas IFNγ and IL1ß were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy. Conclusions: IFNγ and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity. PMID:15539410
Martínez López, Juan Antonio; García Vivar, M Luz; Cáliz, Rafael; Freire, Mercedes; Galindo, María; Hernández, Maria Victoria; López Longo, Francisco Javier; Martínez Taboada, Víctor; Pego Reigosa, Jose María; Rubio, Esteban; Trujillo, Elisa; Vela-Casasempere, Paloma
To develop recommendations on the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, post-partum and breastfeeding based on the best evidence and experience. Recommendations were generated using nominal group and Delphi techniques. An expert panel of 12 rheumatologists was established. A systematic literature review and a narrative review (websites, clinical guidelines and other relevant documentation) were performed and presented to the panel in its 1(st) meeting to be discussed and to help define recommendations. A first draft of recommendations was generated and circulated for comments and wording refinement. A national survey analyzing different aspects of this topic was undertaken separately, followed by a Delphi process (2 rounds). Agreement with each recommendation was ranked on a scale of 1 (total disagreement) to 10 (total agreement), and was considered to be achieved if at least 70% voted≥7. The level of evidence and grade of recommendation were assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. A total of 14 recommendations were generated for the preconception period (oral and hormonal contraception, reproductive techniques), pregnancy (planning, treatment and follow-up), and breastfeeding (treatment and follow-up). High-risk situations such as lupus or antiphospholipid syndrome were included. A consensus>90% was reached for all but one recommendation. These recommendations are intended to provide rheumatologists, patients, families and other stakeholders with a consensus on the evaluation and management of patients with autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
Patients with a rheumatic disease are considered to be at high risk of developing skin problems because of their restricted mobility, vascular complications and the type of medication they are taking.
Birtane, Murat; Yavuz, Selçuk; Taştekin, Nurettin
Autoantibodies can help clinicians to allow early detection of autoimmune diseases and their clinical manifestations, to determine effective monitoring of prognosis and the treatment response. From this point, they have a high impact in rheumatic disease management. When used carefully they allow rapid diagnosis and appropriate treatment. However, as they may be present in healthy population they may cause confusion for interpreting the situation. False positive test results may lead to wrong treatment and unnecessary anxiety for patients. Autoantibody positivity alone does not make a diagnosis. Similarly, the absence of autoantibodies alone does not exclude diagnosis. The success of the test is closely related to sensitivity, specificity and likelihood ratios. So, interpretation of these is very important for a proper laboratory evaluation. In conclusion, in spite of the remarkable advances in science and technology, a deeply investigated anamnesis and comprehensive physical examination still continue to be the best diagnostic method. The most correct approach is that clinicians apply laboratory tests to confirm or exclude preliminary diagnosis based on anamnesis and physical examination. This review will discuss these issues.
Birtane, Murat; Yavuz, Selçuk; Taştekin, Nurettin
Autoantibodies can help clinicians to allow early detection of autoimmune diseases and their clinical manifestations, to determine effective monitoring of prognosis and the treatment response. From this point, they have a high impact in rheumatic disease management. When used carefully they allow rapid diagnosis and appropriate treatment. However, as they may be present in healthy population they may cause confusion for interpreting the situation. False positive test results may lead to wrong treatment and unnecessary anxiety for patients. Autoantibody positivity alone does not make a diagnosis. Similarly, the absence of autoantibodies alone does not exclude diagnosis. The success of the test is closely related to sensitivity, specificity and likelihood ratios. So, interpretation of these is very important for a proper laboratory evaluation. In conclusion, in spite of the remarkable advances in science and technology, a deeply investigated anamnesis and comprehensive physical examination still continue to be the best diagnostic method. The most correct approach is that clinicians apply laboratory tests to confirm or exclude preliminary diagnosis based on anamnesis and physical examination. This review will discuss these issues. PMID:28396844
Zhong, Danli; Wu, Chanyuan; Zeng, Xiaofeng; Wang, Qian
Rheumatic diseases refer to many diseases with a loss of immune self-tolerance, leading to a chronic inflammation, degeneration, or metabolic derangement in multiple organs or tissues. The cause of rheumatic diseases remains to be elucidated, though both environmental and genetic factors are required for the development of rheumatic diseases. Over the past decades, emerging studies suggested that alteration of intestinal microbiota, known as gut dysbiosis, contributed to the occurrence or development of a range of rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjogren's syndrome, through profoundly affecting the balance between pro- and anti-inflammatory immune responses. In this article, we discussed the role of gut microbiota in the pathogenesis of rheumatic diseases based on a large number of experimental and clinical materials, thereby providing a new insight for microbiota-targeted therapies to prevent or cure rheumatic diseases.
Knox, J D
Patients with rheumatic complaints are the subject of some 10% of the general practitioner's work. Approximately half of this work is related to the hitherto relatively neglected group of varied soft-tissue conditions, most of which are self-limiting and of a minor nature. Against a background of such diagnostic 'noise', the general practitioner has to remain alert for the fainter 'signal' of serious disease--rheumatic and non-rheumatic--at an early stage. Continuity of care calls on special qualities, behaviours and abilities in the doctor to boost and maintain morale, to coordinate management and to participate in team care. In addition to more traditional therapeutic measures, including analgesics, NSAIDs, disease-modifying drugs and physiotherapy, joint replacement is seen as a significant contribution. There is room for improvement in the structure process and outcomes of delivery of care as it may relate to rheumatic diseases. A simple illustration, based on a general practice audit of gout, is suggested as a possible model by which quality of care could be enhanced at the level of individual patients. While there is not a great deal of scope afforded to the general practitioner in the exercise of primary prevention of the rheumatic diseases, early diagnosis and timely support for carers of patients suffering from chronic rheumatic diseases are areas worth attention. Promotion of self-help is seen as a worthwhile activity in humanitarian and economic terms, though it calls for an appropriate balance to be struck.
Coit, Patrick; Sawalha, Amr H
The human microbiome consists of the total diversity of microbiota and their genes. High-throughput sequencing has allowed for inexpensive and rapid evaluation of taxonomic representation and functional capability of the microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be influenced by host genetics and environmental factors. Dysbiosis is also associated with shifts in certain functional pathways. The goal of this article is to provide a current and comprehensive review of the unique characteristics of the microbiome of patients with autoimmune and inflammatory rheumatic diseases, measured using high-throughput sequencing. We also highlight the need for broader studies utilizing a longitudinal approach to better understand how the human microbiome contributes to disease susceptibility, and to characterize the role of the interaction between host genetics and microbial diversity in the pathogenesis of autoimmune diseases, disease manifestations, and progression.
Carapetis, Jonathan R; Zühlke, Liesl J
We now stand at a critical juncture for rheumatic fever (RF) and rheumatic heart disease (RHD) control. In recent years, we have seen a surge of interest in these diseases in regions of the world where RF/RHD mostly occur. This brings real opportunities to make dramatic progress in the next few years, but also real risks if we miss these opportunities. Most public health and clinical approaches in RF/RHD arose directly from programmes of research. Many unanswered questions remain, including those around how to implement what we know will work, so research will continue to be essential in our efforts to bring a global solution to this disease. Here we outline our proposed research priorities in RF/RHD for the coming decade, grouped under the following four challenges: Translating what we know already into practical RHD control; How to identify people with RHD earlier, so that preventive measures have a higher chance of success; Better understanding of disease pathogenesis, with a view to improved diagnosis and treatment of ARF and RHD; and Finding an effective approach to primary prevention. We propose a mixture of basic, applied, and implementation science. With concerted efforts, strong links to clinical and public health infrastructure, and advocacy and funding support from the international community, there are good prospects for controlling these RF and RHD over the next decade. PMID:21677798
Beaudoin, Amanda; Edison, Laura; Introcaso, Camille E; Goh, Lucy; Marrone, James; Mejia, Amelita; Van Beneden, Chris
Acute rheumatic fever is a nonsuppurative, immune-mediated consequence of group A streptococcal pharyngitis (strep throat). Recurrent or severe acute rheumatic fever can cause permanent cardiac valve damage and rheumatic heart disease, which increases the risk for cardiac conditions (e.g., infective endocarditis, stroke, and congestive heart failure). Antibiotics can prevent acute rheumatic fever if administered no more than 9 days after symptom onset. Long-term benzathine penicillin G (BPG) injections are effective in preventing recurrent acute rheumatic fever attacks and are recommended to be administered every 3-4 weeks for 10 years or until age 21 years to children who receive a diagnosis of acute rheumatic fever. During August 2013, in response to anecdotal reports of increasing rates of acute rheumatic fever and rheumatic heart disease, CDC collaborated with the American Samoa Department of Health and the Lyndon B. Johnson Tropical Medical Center (the only hospital in American Samoa) to quantify the number of cases of pediatric acute rheumatic fever and rheumatic heart disease in American Samoa and to assess the potential roles of missed pharyngitis diagnosis, lack of timely prophylaxis prescription, and compliance with prescribed BPG prophylaxis. Using data from medical records, acute rheumatic fever incidence was calculated as 1.1 and 1.5 cases per 1,000 children aged ≤18 years in 2011 and 2012, respectively; 49% of those with acute rheumatic fever subsequently received a diagnosis of rheumatic heart disease. Noncompliance with recommended prophylaxis with BPG after physician-diagnosed acute rheumatic fever was noted for 22 (34%) of 65 patients. Rheumatic heart disease point prevalence was 3.2 cases per 1,000 children in August 2013. Establishment of a coordinated acute rheumatic fever and rheumatic heart disease control program in American Samoa, likely would improve diagnosis, treatment, and patient compliance with BPG prophylaxis.
Østensen, Monika; Villiger, Peter M; Förger, Frauke
During pregnancy, the fetus represents a natural allograft that is not normally rejected. While the maternal immune system retains the ability to respond to foreign antigens, tolerance mechanisms are up-regulated to protect the fetus from immunologic attacks by the mother. The profound immunologic adaptations during and after pregnancy do influence maternal autoimmune rheumatic diseases in several ways. One is triggering the onset of a rheumatic disease in the post partum period, the other influencing disease activity of established rheumatic disease. The review will discuss the mechanisms of increased susceptibility of rheumatoid arthritis (RA) in the first year post partum with a specific emphasis on the role of fetal cells or antigens persisting in the maternal circulation (so called microchimerism). Furthermore, the different influences of pregnancy on established rheumatic diseases will be highlighted. A marked beneficial effect of pregnancy is observed on RA whereas several other rheumatic diseases as ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) show either no particular effect or an aggravation of symptoms during pregnancy. Differences emerging in regard to modulation of disease symptoms during pregnancy seem related to response to hormones, the type of cytokine profile and immune response prevailing as well as further downstream interactions of molecular pathways that are important in disease pathogenesis.
Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M
Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.
Shirota, Y; Illei, GG; Nikolov, NP
Many rheumatologic disorders, most notably Sjögren's syndrome, are associated with dental complications and in some cases oral diseases may trigger or drive connective tissue disease. During the past three decades the treatment in rheumatology was revolutionized by the introduction of disease-modifying anti-rheumatic drugs. Advances in our understanding of the pathogenesis of rheumatic diseases have led to the discovery of critical mechanisms of inflammation and autoimmunity and the invention of new target-specific biologic agents. In this review, we will summarize the current state of biologic therapies in rheumatology and discuss the implications of these on oral health and disease. PMID:18282173
White, Harvey; Walsh, Warren; Brown, Alex; Riddell, Tania; Tonkin, Andrew; Jeremy, Richmond; Brieger, David; Zeitz, Chris; Kritharides, Leonard
Rates of acute rheumatic fever and chronic rheumatic heart disease in Aboriginal people, Torres Strait Islanders and Māori continue to be unacceptably high. The impact of rheumatic heart disease is inequitable on these populations as compared with other Australians and New Zealanders. The associated cardiac morbidity, including the development of rheumatic valve disease, and cardiomyopathy, with possible sequelae of heart failure, development of atrial fibrillation, systemic embolism, transient ischaemic attacks, strokes, endocarditis, the need for interventions including cardiac surgery, and impaired quality of life, and shortened life expectancy, has major implications for the individual. The adverse health and social effects may significantly limit education and employment opportunities and increase dependency on welfare. Additionally there may be major adverse impacts on family and community life. The costs in financial terms and missed opportunities, including wasted young lives, are substantial. Prevention of acute rheumatic fever is dependent on the timely diagnosis and treatment of sore throats and skin infections in high-risk groups. Both Australia and New Zealand have registries for acute rheumatic fever but paradoxically neither includes all cases of chronic rheumatic heart disease many of whom would benefit from close surveillance and follow-up. In New Zealand and some Australian States there are programs to give secondary prophylaxis with penicillin, but these are not universal. Surgical outcomes for patients with rheumatic valvular disease are better for valve repair than for valve replacement. Special attention to the selection of the appropriate valve surgery and valve choice is required in pregnant women. It may be necessary to have designated surgical units managing Indigenous patients to ensure high rates of surgical repair rather than valve replacement. Surgical guidelines may be helpful. Long-term follow-up of the outcomes of surgery in
Rodio, Donatella Maria; Anzivino, Elena; Mischitelli, Monica; Bellizzi, Anna; Scrivo, Rossana; Scribano, Daniela; Conte, Gianlorenzo; Prezioso, Carla; Trancassini, Maria; Valesini, Guido; Palamara, Anna Teresa; Pietropaolo, Valeria
Chronic inflammatory rheumatic diseases (CIRDs) are immune-mediated pathologies involving joints. To date, TNFα-blocking agents administration is the most promising therapy, although these treatments are associated with an increased Polyomavirus JC (JCPyV) reactivation, the etiological agent of the Progressive Multifocal Leukoencephalopathy (PML). The aim of this study was the recruitment and the analysis of a CIRDs cohort in order to investigate a possible correlation between JCPyV presence and the influence of anti-TNF-α agents on viral loads. Blood and urine samples were collected from 34 CIRDs subjects prior the first anti-TNF-α infusion (T0) and after 3 (T3), 6 (T6), 12 (T12), and 18 (T18) months. Results showed persistent JC viruria significantly higher than JC viremia throughout the 18 month follow-up study (p = 0.002). In JCPyV positive samples, the non-coding control region (NCCR) was analyzed. Results evidenced archetypal structures (type II-S) in all isolates with the exception of a sequence isolated from a plasma sample, that corresponds to the type II-R found in PML subjects. Finally, the viral protein 1 (VP1) genotyping was performed and results showed the prevalence of the European genotypes 1A, 1B, and 4. Since only few studies have been carried out to understand whether there is a PML risk in CIRDs population infected by JCPyV, this study contributes to enrich literature insight on JCPyV biology in this cluster. Further investigations are necessary in order to recognize the real impact of biologics on JCPyV life cycle and to identify possible and specific viral variants related to increased virulence in CIRDs patients. PMID:27242700
Lourenço, Benito; Kozu, Katia T; Leal, Gabriela N; Silva, Marco F; Fernandes, Elisabeth G C; França, Camila M P; Souza, Fernando H C; Silva, Clovis A
Contraception is an important issue and should be a matter of concern in every medical visit of adolescent and young patients with chronic rheumatic diseases. This narrative review discusses contraception methods in adolescents with juvenile systemic lupus erythematosus (JSLE), antiphospholipid syndrome (APS), juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). Barrier methods are safe and their use should be encouraged for all adolescents with chronic rheumatic diseases. Combined oral contraceptives (COC) are strictly prohibited for JSLE and APS patients with positive antiphospholipid antibodies. Reversible long-acting contraception can be encouraged and offered routinely to the JSLE adolescent patient and other rheumatic diseases. Progestin-only pills are safe in the majority of rheumatic diseases, although the main concern related to its use by adolescents is poor adherence due to menstrual irregularity. Depot medroxyprogesterone acetate injections every three months is a highly effective contraception strategy, although its long-term use is associated with decreased bone mineral density. COC or other combined hormonal contraceptive may be options for JIA and JDM patients. Oral levonorgestrel should be considered as an emergency contraception method for all adolescents with chronic rheumatic diseases, including patients with contraindication to COC. Copyright © 2016. Published by Elsevier Editora Ltda.
Lourenço, Benito; Kozu, Katia T; Leal, Gabriela N; Silva, Marco F; Fernandes, Elisabeth G C; França, Camila M P; Souza, Fernando H C; Silva, Clovis A
Contraception is an important issue and should be a matter of concern in every medical visit of adolescent and young patients with chronic rheumatic diseases. This narrative review discusses contraception methods in adolescents with juvenile systemic lupus erythematosus (JSLE), antiphospholipid syndrome (APS), juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). Barrier methods are safe and their use should be encouraged for all adolescents with chronic rheumatic diseases. Combined oral contraceptives (COC) are strictly prohibited for JSLE and APS patients with positive antiphospholipid antibodies. Reversible long-acting contraception can be encouraged and offered routinely to the JSLE adolescent patient and other rheumatic diseases. Progestin-only pills are safe in the majority of rheumatic diseases, although the main concern related to its use by adolescents is poor adherence due to menstrual irregularity. Depot medroxyprogesterone acetate injections every three months is a highly effective contraception strategy, although its long-term use is associated with decreased bone mineral density. COC or other combined hormonal contraceptive may be options for JIA and JDM patients. Oral levonorgestrel should be considered as an emergency contraception method for all adolescents with chronic rheumatic diseases, including patients with contraindication to COC. Copyright © 2016. Published by Elsevier Editora Ltda.
Kondo, Yuya; Yokosawa, Masahiro; Kaneko, Shunta; Sumida, Takayuki
The most frequent rheumatic joint disease in the elderly is rheumatoid arthritis (RA). Recent advances in the treatment of RA improve prognosis, and gradually increase the elderly patients with RA. There are some differences in clinical features between the patients with elderly onset RA and young onset RA, such as systemic symptoms and distribution of affected joints. In addition, it is occasionally difficult to differentiate elderly onset RA from the other rheumatic diseases like polymyalgia rheumatica and RS3PE syndrome, pseudogout, and osteoarthritis. Since elderly patients tend to have more co-morbidity and co-existing diseases requiring treatment with other drugs, a risk/benefit profile must always be taken into consideration when choosing the treatment in elderly patients with rheumatic joint diseases.
Damage-associated molecular patterns (DAMPs) are chemically heterogeneous endogenous host molecules rapidly released from damaged or dying cells that incite a sterile inflammatory response mediated via pattern recognition receptors (PRRs). The sources of DAMPs are dead or dying cells or the extracellular matrix and can signal through the PRRs, the Toll-like receptors or cytosolic Nod-like receptors, culminating in nuclear factor κB (NF-κB) activation and pro-inflammatory cytokine secretion. Together, these molecules are involved in sterile inflammation and many are associated with rheumatic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythromatosus, psoriatic arthritis and systemic sclerosis. These diseases are associated with inflammation and many danger signals are found in sites of sterile inflammation and mediate inflammation. The present review examines the role of DAMPs in rheumatic conditions and suggests avenues for their therapeutic modulation.
Abrão, Aline Lauria Pires; Santana, Caroline Menezes; Bezerra, Ana Cristina Barreto; Amorim, Rivadávio Fernandes Batista de; Silva, Mariana Branco da; Mota, Licia Maria Henrique da; Falcão, Denise Pinheiro
Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases.
Abrão, Aline Lauria Pires; Santana, Caroline Menezes; Bezerra, Ana Cristina Barreto; Amorim, Rivadávio Fernandes Batista de; Silva, Mariana Branco da; Mota, Licia Maria Henrique da; Falcão, Denise Pinheiro
Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases.
... Immune System & Its Link to Rheumatic Disease The Immune System and Its Link to Rheumatic Disease Fast Facts ... of a vessel of the body). What’s the immune system? The immune system allows us to identify and ...
Suurmond, Jolien; van der Velden, Daniël; Kuiper, Johan; Bot, Ilze; Toes, René E M
Rheumatoid Arthritis is a chronic autoimmune disease with a complex disease pathogenesis leading to inflammation and destruction of synovial tissue in the joint. Several molecules lead to activation of immune pathways, including autoantibodies, Toll-Like Receptor ligands and cytokines. These pathways can cooperate to create the pro-inflammatory environment that results in tissue destruction. Each of these pathways can activate mast cells, inducing the release of a variety of inflammatory mediators, and in combination can markedly enhance mast cell responses. Mast cell-derived cytokines, chemokines, and proteases have the potential to induce recruitment of other leukocytes able to evoke tissue remodeling or destruction. Likewise, mast cells can secrete a plethora of factors that can contribute to tissue remodeling and fibroblast activation. Although the functional role of mast cells in arthritis pathogenesis in mice is not yet elucidated, the increased numbers of mast cells and mast cell-specific mediators in synovial tissue of rheumatoid arthritis patients suggest that mast cell activation in rheumatoid arthritis may contribute to its pathogenesis.
Kumar, R Krishna; Tandon, R
Rheumatic fever (RF) and rheumatic heart disease (RHD) continue to be a major health hazard in most developing countries as well as sporadically in developed economies. Despite reservations about the utility, echocardiographic and Doppler (E&D) studies have identified a massive burden of RHD suggesting the inadequacy of the Jones' criteria updated by the American Heart Association in 1992. Subclinical carditis has been recognized by E&D in patients with acute RF without clinical carditis as well as by follow up of RHD patients presenting as isolated chorea or those without clinical evidence of carditis. Over the years, the medical management of RF has not changed. Paediatric and juvenile mitral stenosis (MS), upto the age of 12 and 20 yr respectively, severe enough to require operative treatement was documented. These negate the belief that patients of RHD become symptomatic ≥20 years after RF as well as the fact that congestive cardiac failure in childhood indicates active carditis and RF. Non-surgical balloon mitral valvotomy for MS has been initiated. Mitral and/or aortic valve replacement during active RF in patients not responding to medical treatment has been found to be life saving as well as confirming that congestive heart failure in acute RF is due to an acute haemodynamic overload. Pathogenesis as well as susceptibility to RF continue to be elusive. Prevention of RF morbidity depends on secondary prophylaxis which cannot reduce the burden of diseases. Primary prophylaxis is not feasible in the absence of a suitable vaccine. Attempts to design an antistreptococcal vaccine utilizing the M-protein has not succeeded in the last 40 years. Besides pathogenesis many other questions remain unanswered.
Westhovens, Rene; Annemans, Lieven
The cost of drugs is becoming an issue worldwide, in particular for inflammatory rheumatic diseases. In the current review, an overview of the scene is given with a specific emphasis on accessibility for those patients in real need of the available expensive treatments. The authors propose 7 principles for discussion that need to be addressed and are a responsibility for all stakeholders in rheumatology. PMID:27651923
Imaeda, Hiroyuki; Ishii, Hiromasa; Goto, Makoto
Rheumatic diseases often have gastrointestinal(GI) manifestations, and may present as GI bleeding and perforation due to peptic ulcer associated with high mortality. Major causes of peptic ulcer related to rheumatic diseases are drugs such as nonsteroidal anti-inflammatory drug(NSAID) and corticosteroid, and vasculitis. The analgesic effects of NSAID often mask abdominal pain until they cause GI bleeding and perforation. Therefore, it is important to make early diagnosis of peptic ulcer with upper gastrointestinal endoscope. Fundamental treatment of NSAID induced peptic ulcer is to quit it, however it is difficult because of activity of rheumatic diseases. Also, most NSAID induced peptic ulcers heal by administration of proton pump inhibitor or misoprostol. Corticosteroid pulse therapy or administration of immunosuppressant agents is effective for vasculitis induced peptic ulcer, however it is difficult to make diagnosis of it. Development of NSAID with less side effects such as cyclooxygenase-2 selective inhibitors and establishment of diagnosis and treatment of peptic ulcer related to rheumatic diseases are expected.
Fabri, Gisele M C; Savioli, Cynthia; Siqueira, José T; Campos, Lucia M; Bonfá, Eloisa; Silva, Clovis A
Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
Tai chi is a complex multicomponent mind-body exercise. Many studies have provided evidence that tai chi benefits patients with a variety of chronic disorders. This form of mind-body exercise enhances cardiovascular fitness, muscular strength, balance, and physical function and seems to be associated with reduced stress, anxiety, and depression and improved quality of life. Thus, despite certain limitations in the evidence, tai chi can be recommended to patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia as a complementary and alternative medical approach. This article overviews the current knowledge about tai chi to better inform clinical decision making for rheumatic patients. Copyright Â© 2011 Elsevier Inc. All rights reserved.
Li, Sophia; Micheletti, Robert
Millions of people suffer from rheumatic diseases such as gout, fibromyalgia, osteoarthritis, and rheumatoid arthritis. These can be incapacitating and detrimental to quality of life. Diet, nutrition, and weight loss have shown promise in alleviating some of this disease burden. These lifestyle changes may give patients a feeling of control and ownership over their disease as well as a nonpharmacologic means of treatment. This article reviews the available research on the effects of diet and nutrition on rheumatoid disease.
Baillargeon, Jacques; Al Snih, Soham; Raji, Mukaila A; Urban, Randall J; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S; Baillargeon, Gwen; Kuo, Yong-Fang
Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation's largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.
Robazzi, Teresa Cristina Martins Vicente; Adan, Luis Fernando Fernandes
Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with rheumatologic autoimmune diseases, such as Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus and scleroderma. Limited data are available regarding the prevalence and clinical characteristics of autoimmune thyroiditis in other rheumatologic disorders, such as rheumatic fever and juvenile systemic lupus erythematosus. The authors review the association of endocrine autoimmune and rheumatic autoimmune diseases, assessing various age groups and clinical conditions. The bibliographic survey was conducted through the search for scientific articles indexed in the general health sciences databases, such as Latin American and Caribbean Health Sciences Literature (LILACS), Medline/PubMed, and Scientific Electronic Library Online (SciELO). The following descriptors were used: "rheumatic autoimmune diseases and autoimmune thyroid diseases"; "thyroid disorders and rheumatic diseases"; "thyroiditis and rheumatic diseases"; "autoimmune diseases and thyroid"; and "pediatric rheumatic diseases and autoimmune thyroid diseases". This study showed that, despite contradictory results in the literature, there is a greater prevalence of the association between autoimmune thyroid diseases and rheumatic diseases, highlighting the possibility of common pathogenic mechanisms among them.
Monjardino, Teresa; Lucas, Raquel; Barros, Henrique
that indicates an important burden of rheumatic diseases in the general Portuguese population. Gaps were identified particularly regarding inflammatory arthropathies and other systemic rheumatic diseases.
Baker, Joshua F; Ghio, Andrew J
Iron is critical in nearly all cell functions and the ability of a cell, tissue and organism to procure this metal is obligatory for survival. Iron is necessary for normal immune function, and relative iron deficiency is associated with mild immunosuppression. Concentrations of this metal in excess of those required for function can present both an oxidative stress and elevate risks for infection. As a result, the human has evolved to have a complex mechanism of regulating iron and limiting its availability. This homoeostasis can be disrupted. Autoimmune diseases and gout often present with abnormal iron homoeostasis, thus supporting a participation of the metal in these injuries. We review the role of iron in normal immune function and discuss both clinical evidence of altered iron homoeostasis in autoimmune diseases and gout as well as possible implications of both depletion and supplementation of this metal in this patient population. We conclude that altered iron homoeostasis may represent a purposeful response to inflammation that could have theoretical anti-inflammatory benefits. We encourage physicians to avoid routine iron supplementation in those without depleted iron stores.
Woo, Patricia; Colbert, Robert A.
The evidence so far suggests that the paediatric inflammatory diseases encountered in rheumatology practice may be largely genetic in origin, where common single nucleotide polymorphisms (SNPs) in multiple genes contribute to risk, with real but variable environmental components. As far as genetic susceptibility to common paediatric rheumatic diseases is concerned, only juvenile idiopathic arthritis (JIA) has been investigated in any substantial way so far. This article discusses susceptibility for different types of JIA, the different methods used and their advantages and disadvantages. The genetic code is also modifiable by epigenetic mechanisms and examples of these in immunity and rheumatoid arthritis are given to indicate another area of research in the elucidation of the genetics of paediatric rheumatic diseases. PMID:19853825
Müller, W; Fiebich, B L; Stratz, T
Various rheumatic diseases like fibromyalgia, systemic inflammatory rheumatic disorders and localized diseases, such as arthritides and activated arthroses, tendinopathies and periarthropathies, as well as trigger points can be improved considerably by treatment with the 5-HT3 receptor antagonist tropisetron. Particularly in the latter group of diseases, local injections have done surprisingly rapid analgesic action. This effect matches that of local anesthetics, but lasts considerably longer and is comparable to local injections of local anesthetics combined with corticosteroids. The action of the 5-HT3 receptor antagonists can be attributed to an antinociceptive effect that occurs at the same time as an antiphlogistic and probably also an immunosuppressive effect. Whereas an inhibited release of substance P from the nociceptors, and possibly some other neurokins as well, seems to be the most likely explanation for the antinociceptive action, the antiphlogistic effect is primarily due to an inhibited formation of various different phlogistic substances; in some conditions, like systemic inflammatory rheumatic diseases, for example, the 5-HT3 receptor antagonists may exert an immunosuppressive effect in addition to this.
Onishi, Takahisa; Idei, Yuka; Otsui, Kazunori; Iwata, Sachiyo; Suzuki, Atsushi; Ozawa, Toru; Domoto, Koji; Takei, Asumi; Inamoto, Shinya; Inoue, Nobutaka
Patient: Male, 76 Final Diagnosis: Rheumatic valvular heart disease Symptoms: Breathlessness and leg edema Medication: — Clinical Procedure: Medical treatment for heart failure Specialty: Cardiology Objective: Rare disease Background: Complete calcification of the left atrium (LA) is called “coconut atrium”, which decreases the compliance of LA, leading to the elevation of LA pressure that is transmitted to the right-side of the heart. The pathogenesis of LA calcification in patients with rheumatic heart disease is unknown; however, possible mechanisms include chronic strain force in the atrial wall and inflammation. We report here a patient with long-standing rheumatic valvular heart disease with coconut atrium. Case Report: A 76-year-old man presented with breathlessness and leg edema due to right-sided heart failure. He was diagnosed with rheumatic fever at 8 years of age. Mitral commissurotomy and the mitral and aortic valve replacement were previously performed to treat mitral and aortic valvular stenosis. The profile view of the chest X-ray indicated a diffuse calcified outline of the LA wall. A transthoracic echocardiogram revealed pulmonary hyper-tension and dilatation of both atria. Moreover, computed tomography showed nearly circumferential calcification of the LA wall. Despite intense medical treatment, he succumbed to heart failure. An autopsy demonstrated that the LA was markedly dilated, its wall was calcified, and its appearance was similar to the surface of an atherosclerotic aorta. Microscopic examination revealed intensive calcification in the endocardium. Minimal accumulation of inflammatory cells was noted. Although slight fibrosis was observed, the cardiac musculature was preserved. Conclusions: To the best of our knowledge, this is the first report that identifies the histological changes of LA calcification associated with long-standing rheumatic valvular heart disease. PMID:25819539
Mussano, Eduardo D; Onetti, Laura B; Cadile, Isaac I; Onetti, Carlos M
Preparations of intravenous immunoglobulin (IVIG) are used as treatment in different diseases such primary and secondary immunodeficiencies, autoimmune diseases, systemic inflammatory diseases, infectious diseases and allergic diseases among others. to present 13 of our cases with the use of IVIG in different rheumatic diseases. we retrospectively studied 13 patients (10 women and 3 men), mean age 29 years with different rheumatic diseases, that underwent conventional treatments without positive response. They received IVIG pulses, trying to improve or induce remission of their previous clinical situation. 6/13 patients met criteria for systemic lupus erythematosus (SLE), 2/13 had primary antiphospholipid syndrome (APL)one had polydermatomyositis (PDM), 1 juvenile arthritis, 1 panarteritis nodosa (cutaneous PAN), one Evans syndrome, and one with autoimmune uveitis. 7 of them had a positive response to therapy with IGEV evaluated by clinical and biochemical parameters. They remained with conventional treatments. One patient received a new IG EV pulse after 24 months, because of panniculitis reactivation. Clinical and biochemical response was poor in 4 of them, and 2 patients died. IVIg may be usefull in autoimmune rheumatic diseases when conventional therapies have failed. The therapeutic success is also limited. Only the 55 percent of our patients had a positive clinical response.
Sharma, Neha; Toor, Devinder
Streptococcus pyogenes (group A streptococcus) causes rheumatic fever (RF) which later progresses towards rheumatic heart disease (RHD) in the susceptible individuals. RF and RHD both contribute towards increasing global burden of disease, especially in developing countries. RHD is one of the most common acquired heart diseases causing permanent damage to heart valves which ultimately leads to heart failure. In RHD, heart valve lesions are formed which are mediated by autoimmune reaction between streptococcal antigens (M protein and group A carbohydrate epitope GlcNAc) and heart tissues. On the other hand, inflammatory response generated by cytokines promotes chronicity of the disease. Varying concentrations of interleukin-10 (IL-10) in patients and controls are reported and are also found to be associated with IL-10 gene polymorphism in RF/RHD patients. Although the effect of IL-10 gene polymorphism on the functionality of IL-10 is unknown, many investigations suggest an important role of IL-10 and its polymorphism in immune regulation and progression of disease in RF/RHD. This review summarizes the studies based on association of interleukin-10 with RHD in different populations to understand the role of IL-10 in susceptibility and pathogenesis of the disease.
Ribitsch, V; Rainer, F; Ribitsch, G; Schurz, J; Klein, G
The rheological properties of synovial fluids from patients with different rheumatic diseases are discussed. Viscosities of 73 samples were determined and are compared to a standard of "healthy" human synovial fluid p. m. and to bovine synovia. Typical differences between "healthy", degenerative and inflammatory synovial fluids could be discerned. These differences can be characterized with several rheological parameters. The mechanism of lubrication in joints and the role of synovial fluid as a lubricant are discussed. Rheological properties of polymere solutions which could serve as a substitute for sick synovial fluids are described and compared to the properties of healthy synovia. Several possibilities for molecular changes which could account for the deterioration of synovial fluids in patients with different rheumatic diseases are discussed.
Pedersen, L M; Permin, H
The painters Rubens, Renoir, and Dufy suffered from rheumatoid arthritis and Klee from scleroderma. Analysis of the areas of various colours in randomly selected paintings by these four artists and by eight "controls" (contemporary painters without rheumatic disease) suggests that Rubens, Renoir, Dufy, and Klee used significantly more bright and clear colours based on toxic heavy metals and fewer earth colours containing harmless iron and carbon compounds. These four painters may have been heavily exposed to mercury sulphide, cadmium sulphide, arsenic sulphide, lead, antimony, tin, cobalt, manganese, and chromium, the metals of the bright and clear colours, and exposure to these metals may be of importance in the development of inflammatory rheumatic diseases. Artists today are not so exposed, but heavy metal contamination in food and drinking water exists and experience from the occupational exposure of old masters is still relevant.
Yokota, Shumpei; Kikuchi, Masako; Nozawa, Tomo; Kizawa, Toshitaka; Kanetaka, Taichi; Kadota, Keisuke; Miyamae, Takako; Mori, Masaaki
Fever is one of the critical symptoms of patients in pediatrics field. It indicates inflammatory focus somewhere in the body, and the major causes of fever are infectious diseases. Recent progresses of our knowledge about autoinflammatory syndrome promoted the investigation of the mechanism of fever, and suggested that the pro-inflammatory cytokines are the direct causative agents of fever. The basic science revealed that cooperation of IL-6 and IL-1β induces febrile response. Fever of unknown origin (FUO) remains a challenging problem. Rheumatic diseases, rare infectious diseases, and benign tumors and malignancies are diagnoses to be differentiated. FDG-PET is recently proved a valuable tool for the identification of the etiology in patients with FUO. Since the introduction of biological response modifiers into the treatment of patients with pediatric rheumatic diseases has shifted the therapeutic paradigm, a new concept that the blockade of a unique pro-inflammatory cytokine brings cessation of whole inflammatory responses affected tremendously the clinical medicine. A more investigation of inflammation and its pathophisiology will be needed in pediatric rheumatology.
Schiotis, RE; Buzoianu, AD; Mureșanu, DF; Suciu, S
Targeting the pathogenic pathway of chronic inflammation represents an unmet challenge for controlling disease activity, preventing functional disability, and maintaining an adequate quality of life in patients with rheumatic diseases. Abatacept, a novel molecule that inhibits co-stimulation signal, induces an inhibitory effect on the T-cells. This will further interfere with the activity of several cell lines, leading to the normalization of the immune response. In the latest years, abatacept has been extensively investigated in studies of rheumatoid arthritis for which it was recently approved as a second line biologic treatment in Romania. This review presents the clinical efficacy of abatacept in several rheumatic diseases and highlights the safety profile of this biological agent. Abbreviations: ACR = American College of Rheumatology, ADR = Adverse drug reaction, APC = antigen presenting cell, ApS = psoriatic arthritis, CRP = C reactive protein, CTLA-4 = Cytotoxic T-Cell Lymphocyte Antigen-4, DAS = Disease activity score, DMARDs = Disease modifying antirheumatic drugs, EMA = European Medicine Agency, EULAR = European League Against Rheumatism, FDA = Food and Drugs Administration, HBV = Hepatitis B virus, JIA = Juvenile Idiopathic Arthritis, LDA = low disease activity (LDA), MRI = magnetic resonance imaging (MRI), MTX = methotrexate, RA = rheumatoid arthritis, RCT = randomized controlled trial, SS = Sjogren’s syndrome, TCR = T cell receptor PMID:27974925
Seckeler, Michael D; Hoke, Tracey R
Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are significant public health concerns around the world. Despite decreasing incidence, there is still a significant disease burden, especially in developing nations. This review provides background on the history of ARF, its pathology and treatment, and the current reported worldwide incidence of ARF and prevalence of RHD. PMID:21386976
Watson, Gabriella; Jallow, Bintou; Le Doare, Kirsty; Pushparajah, Kuberan; Anderson, Suzanne T
Poststreptococcal complications, such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD), are common in resource-limited settings, with RHD recognised as the most common cause of paediatric heart disease worldwide. Managing these conditions in resource-limited settings can be challenging. We review the investigation and treatment options for ARF and RHD and, most importantly, prevention methods in an African setting.
Azizi, Gholamreza; Simhag, Anita; El Rouby, Nadia M M; Mirshafiey, Abbas
Newly identified T helper cell 22 (Th22) is a subset of CD4+T cells with specific properties apart from other known CD4+ T cell subsets with distinguished gene expression and function. Th22 cells are characterized by production of a distinct profile of effector cytokines, including interleukin (IL)-22, IL-13, and tumor necrosis factor-α (TNF-α). The levels of Th22 and related cytokine IL-22 are increased in various autoimmune diseases and positively associated with some rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, behcet's disease, ankylosing spondylitis and psoriatic arthritis. In summary, IL-22 and Th22 cells play a significant and complicated role in inflammatory and autoimmune rheumatic diseases, therefore, targeting IL-22 or Th22 have unique and attractive advantages due to the fact that Th22 subset is recently identified and its associated research is extremely limited. This review discusses the role of Th22 and its cytokine IL-22 in the immunopathogenesis of rheumatic disease.
Sit, Michelle T; Arroyo, Ramon
The objective of this article is to educate military physicians and providers about rare, endemic rheumatic diseases that may be encountered in deployments to the Middle East region, specifically Familial Mediterranean Fever (FMF), Behcet's disease (BD), and tumor necrosis factor-associated periodic syndrome (TRAPS). We found review articles using MDConsult and Ovid. Suitable articles were employed to describe the characteristics of each disease. Although these diseases are considered rare, they can be endemic to current areas of deployment. Awareness of these conditions may prevent unnecessary and invasive treatment as well as make the clinician aware of possible disease complications.
Szekanecz, Zoltán; Szekanecz, Eva; Bakó, Gyula; Shoenfeld, Yehuda
Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases, are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Systemic inflammatory rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma or dermatomyositis, may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. Immunosuppressive drugs and biological agents may also be carcinogenic. However, sustained inflammatory activity seems to be the primary risk factor for malignancies in autoimmune diseases. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in rheumatoid arthritis and other autoimmune diseases.
In rheumatic and other chronic inflammatory diseases, high amounts of energy for the activated immune system have to be provided and allocated by energy metabolism. In recent time many new insights have been gained into the control of the immune response through metabolic signals. Activation of immune cells as well as reduced nutrient supply and hypoxia in inflamed tissues cause stimulation of glycolysis and other cellular metabolic pathways. However, persistent cellular metabolic signals can promote ongoing chronic inflammation and loss of immune tolerance. On the organism level, the neuroendocrine immune response of the hypothalamic-pituitary adrenal axis and sympathetic nervous system, which is meant to overcome a transient inflammatory episode, can lead to metabolic disease sequelae if chronically activated. We conclude that, on cellular and organism levels, a prolonged energy appeal reaction is an important factor of chronic inflammatory disease etiology. PMID:22747923
Abella, Vanessa; Scotece, Morena; López, Verónica; Lazzaro, Verónica; Pino, Jesús; Gómez-Reino, Juan J.; Gualillo, Oreste
The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases. PMID:24741591
Abella, Vanessa; Scotece, Morena; Conde, Javier; López, Verónica; Lazzaro, Verónica; Pino, Jesús; Gómez-Reino, Juan J; Gualillo, Oreste
The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.
Mitchell, K; Kaul, M; Clowse, Megan E B
Pregnancy can create a challenge for physicians caring for women with rheumatic diseases. For many women with rheumatoid arthritis (RA), pregnancy can provide a reprieve from long-term joint pain and inflammation, but others will not experience remission and will continue to need medication. Systemic lupus erythematosus (SLE) may remain quiet in some women, but in others may become more aggressive during pregnancy, putting both mother and foetus at risk. Women with limited scleroderma can do remarkably well, but scleroderma renal crises can be difficult to manage. A third of pregnancies in women with antiphospholipid syndrome (APS) may be refractory to our best therapy. In general, active inflammation from rheumatic diseases poses a stronger threat to the well-being of both mother and foetus than many immunosuppressant medications. Therefore, continued immunosuppression with the least risky medications will allow for the most optimal pregnancy outcomes.
Mitchell, K; Kaul, M; Clowse, MEB
Pregnancy can create a challenge for physicians caring for women with rheumatic diseases. For many women with rheumatoid arthritis (RA), pregnancy can provide a reprieve from long-term joint pain and inflammation, but others will not experience remission and will continue to need medication. Systemic lupus erythematosus (SLE) may remain quiet in some women, but in others may become more aggressive during pregnancy, putting both mother and foetus at risk. Women with limited scleroderma can do remarkably well, but scleroderma renal crises can be difficult to manage. A third of pregnancies in women with antiphospholipid syndrome (APS) may be refractory to our best therapy. In general, active inflammation from rheumatic diseases poses a stronger threat to the well-being of both mother and foetus than many immunosuppressant medications. Therefore, continued immunosuppression with the least risky medications will allow for the most optimal pregnancy outcomes. PMID:20337545
Nulu, Shanti; Bukhman, Gene; Kwan, Gene F
Primarily affecting the young, rheumatic heart disease (RHD) is a neglected chronic disease commonly causing premature morbidity and mortality among the global poor. Standard clinical prevention and treatment is based on studies from the early antimicrobial era, as research investment halted soon after the virtual eradication of the disease from developed countries. The emergence of new global data on disease burden, new technologies, and a global health equity platform have revitalized interest and investment in RHD. This review surveys past and current evidence for standard RHD diagnosis and treatment, highlighting gaps in knowledge. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Gay, Steffen; Wilson, Anthony G
Epigenetics is a key mechanism regulating the expression of genes. There are three main and interrelated mechanisms: DNA methylation, post-translational modification of histone proteins and non-coding RNA. Gene activation is generally associated with lower levels of DNA methylation in promoters and with distinct histone marks such as acetylation of amino acids in histones. Unlike the genetic code, the epigenome is altered by endogenous (e.g. hormonal) and environmental (e.g. diet, exercise) factors and changes with age. Recent evidence implicates epigenetic mechanisms in the pathogenesis of common rheumatic disease, including RA, OA, SLE and scleroderma. Epigenetic drift has been implicated in age-related changes in the immune system that result in the development of a pro-inflammatory status termed inflammageing, potentially increasing the risk of age-related conditions such as polymyalgia rheumatica. Therapeutic targeting of the epigenome has shown promise in animal models of rheumatic diseases. Rapid advances in computational biology and DNA sequencing technology will lead to a more comprehensive understanding of the roles of epigenetics in the pathogenesis of common rheumatic diseases.
Elliott, Amy B; Chakravarty, Eliza F
Systemic rheumatic diseases commonly affect women during the childbearing years. Many women with these diseases may be contemplating pregnancy or discover an inadvertent pregnancy, leading to concerns regarding medication use, changes in disease activity during pregnancy, safety of lactation, and future ability to care for a child given the presence of chronic illnesses. There are outstanding reviews that summarize the safety and use of immunosuppressive medications during pregnancy. However, in addition to medication use, providers need to be aware of the available data regarding fertility, pregnancy outcomes, delivery, and lactation issues that may be specific to individual diseases. Optimally, women should plan pregnancies to occur around times of disease quiescence, several months after potentially teratogenic medications have been discontinued. The course of the underlying rheumatic disease during pregnancy is variable, and there are no specific clinical or laboratory variables that consistently predict disease improvement or worsening during pregnancy. Recent data suggest that increased disease activity in women with most autoimmune diseases during pregnancy may lead to increased risk of premature delivery, low-birth-weight infants, and other adverse pregnancy outcomes. Arthritis involving the cervical spine and hips may impact delivery and must be considered by both obstetricians and obstetric anesthesiologists. Data are mixed regarding the impact of breastfeeding on underlying autoimmune diseases; the choice to continue breastfeeding is a personal decision.
Ribbens, C; Martin, y; Franchimont, N; Kaiser, M; Jaspar, J; Damas, P; Houssiau, F; Malaise, M
Objective: To determine matrix metalloproteinase-3 (MMP-3) serum levels in patients with rheumatic diseases and to study the relation between MMP-3 and C reactive protein (CRP) levels. Methods: MMP-3 serum levels were determined by enzyme linked immunosorbent assay (ELISA) in (a) patients with active inflammatory rheumatic diseases: rheumatoid arthritis (RA), psoriatic arthritis, polymyalgia rheumatica, acute crystal arthritis, and ankylosing spondylitis; (b) patients with active inflammatory systemic diseases: cutaneo-articular or renal systemic lupus erythematosus (SLE), systemic sclerosis, and vasculitides; (c) patients with non-inflammatory rheumatic diseases: osteoarthritis and fibromyalgia; (d) critically ill patients without rheumatic diseases, representing an acute inflammatory control group; (e) healthy controls. Results: MMP-3 serum levels were significantly increased in patients with active RA, psoriatic arthritis, and polymyalgia rheumatica, whether treated or not by corticosteroids, and in female patients with acute crystal arthritis. MMP-3 serum levels were normal in steroid-free patients with active cutaneo-articular or renal SLE, systemic sclerosis, and vasculitides but were significantly increased in steroid treated patients. MMP-3 levels were normal in fibromyalgia, osteoarthritis, ankylosing spondylitis, and acute inflammatory controls. MMP-3 was significantly correlated with CRP in RA (r=0.5, p=0.0004) but not in any of the other disease groups. Conclusions: MMP-3 serum levels are increased in inflammatory rheumatic diseases characterised by joint synovitis, such as RA, polymyalgia rheumatica, psoriatic arthritis, and acute crystal arthritis—that is, whether the diseases are acute or chronic, erosive or not. They are normal in SLE, systemic sclerosis, and vasculitides as well as in non-rheumatic inflammatory controls, but are significantly increased by steroids. These data strongly suggest that serum MMP-3 reflects synovial inflammation. PMID
Kraus, Courtney L.; Culican, Susan M.
Biologic agents have dramatically shifted the treatment paradigm for rheumatic disease. Use of these agents can decrease disease burden, allow the patient to be weaned from corticosteroids, and reduce the likelihood of relapse. Eye disease associated with rheumatic conditions may present with a wide range of signs and symptoms. This coexisting pathology should not be overlooked and should be considered a reason for initiation or continuation of biologic therapy. Additionally, many of the ocular manifestations of rheumatic disease respond preferentially to specific targeting molecules. This paper summarizes the available studies on the use, efficacy, and safety of biologic agents in the treatment of ocular manifestations of rheumatic disease. PMID:22229035
Yeoh, Nigel; Burton, Jeremy P; Suppiah, Praema; Reid, Gregor; Stebbings, Simon
There is a growing understanding of the mechanisms by which the influence of the microbiota projects beyond sites of primary mucosal occupation to other human body systems. Bacteria present in the intestinal tract exert a profound effect on the host immune system, both locally and at distant sites. The oral cavity has its own characteristic microbiota, which concentrates in periodontal tissues and is in close association with a permeable epithelium. In this review we examine evidence which supports a role for the microbiome in the aetiology of rheumatic disease. We also discuss how changes in the composition of the microbiota, particularly within the gastrointestinal tract, may be affected by genetics, diet, and use of antimicrobial agents. Evidence is presented to support the theory that an altered microbiota is a factor in the initiation and perpetuation of inflammatory diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA), and inflammatory bowel disease (IBD). Mechanisms through which the microbiota may be involved in the pathogenesis of these diseases include altered epithelial and mucosal permeability, loss of immune tolerance to components of the indigenous microbiota, and trafficking of both activated immune cells and antigenic material to the joints. The potential to manipulate the microbiome, by application of probiotics and faecal microbial transplant (FMT), is now being investigated. Both approaches are in their infancy with regard to management of rheumatic disease but their potential is worthy of consideration, given the need for novel therapeutic approaches, and the emerging recognition of the importance of microbial interactions with human hosts.
Abella, Vanessa; Pérez, Tamara; Scotece, Morena; Conde, Javier; Pirozzi, Claudio; Pino, Jesús; Lago, Francisca; González-Gay, Miguel Ángel; Mera, Antonio; Gómez, Rodolfo; Gualillo, Oreste
Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in adipose tissue, disturbing its metabolism and the balance of adipokines, related to obesity. The altering secretion pattern of adipokines from the adipose tissue and the increasing mechanical load in weight-bearing joints presented in obesity condition, are risk factors for osteoarthritis development. The most prevalent rheumatic diseases, osteoarthritis and rheumatoid arthritis, are chronic conditions that target the whole joints, leading to increasing disability and health care cost. The goal of this focused review is to summarize the current knowledge on the role of PCBs in osteoarthritis and rheumatoid arthritis pathogenesis. A PubMed search was managed using keywords as "rheumatic diseases", "polychlorinated biphenyls", "obesity" and "endocrine disruption". The incidence of rheumatoid arthritis has been reported to be increased especially in urban areas in industrialized countries, emphasizing the importance of environment in the pathogenesis of rheumatic diseases. Analysis of two cohorts exposed to PCBs food contamination showed high incidence of arthritis. In addition, PCBs in serum correlated positively with the prevalence of self-reported arthritis. Few studies support the hypothesis that osteoarthritis development could be related to PCBs induction of chondrocytes apoptosis. Evidences have emerged for a relationship between PCBs and development of several types of arthritis. Further research is encouraged to determine the correlation between PCBs exposure and the development of rheumatic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.
Gualano, Bruno; Pinto, Ana Lúcia de Sá; Perondi, Maria Beatriz; Roschel, Hamilton; Sallum, Adriana Maluf Elias; Hayashi, Ana Paula Tanaka; Solis, Marina Yazigi; Silva, Clóvis Artur
Over the past decades, the role of exercise training in rheumatic diseases has been largely explored. Currently, physical activity is well known to benefit patients with osteoporosis, osteoarthritis, systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathy, fibromyalgia and rheumatoid arthritis. Therefore, exercise training has been considered a valuable tool for treating rheumatic patients. The therapeutic effects of exercise training have also been investigated in pediatric rheumatic diseases. Collectively, studies have revealed the therapeutic potential of exercise in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis, juvenile fibromyalgia and other causes of chronic pain. The aim of this review is to familiarize the pediatric rheumatologist with the exercise science field; discuss the potential benefits of exercise training in pediatric rheumatic diseases, emphasize both research and clinical perspectives of this promising field; and propose practical models of pre-participation examinations and contraindications to exercise.
Antipa, Ciprian; Moldoveanu, Vladimir; Rusca, Nicolae; Bruckner, Ion I.; Podoleanu, Adrian Gh.; Stanciulescu, Viorica
We tried to establish the efficiency of low energy (power) lasers (LEL), in various inflammatory and noninflammatory rheumatic diseases during five years. We treated 514 patients with osteoarthrosis, 326 patients with nonarticular rheumatism and 82 patients with inflammatory rheumatism, in four different ways: only with Galium-Aluminum-Arsenide (GaAs) infrared lasers; both GaAs lasers and Helium neon (HeNe) lasers; with placebo laser; with classical anti-inflammatory therapy. The results were analyzed using local objective improvements and the score obtained from a pain scale before and after the treatments. We also note some preliminary results obtained by the computer analysis of the evocated potentials after laser irradiation. We conclude that LEL (especially HeNe with GaAs) is obviously more efficient than placebo laser therapy and also had better or at least similar results, in most of the cases, than classical anti-inflammatory therapy.
Østensen, Monika; Andreoli, Laura; Brucato, Antonio; Cetin, Irene; Chambers, Christina; Clowse, Megan E B; Costedoat-Chalumeau, Nathalie; Cutolo, Maurizio; Dolhain, Radboud; Fenstad, M H; Förger, Frauke; Wahren-Herlenius, Marie; Ruiz-Irastorza, Guillermo; Koksvik, Hege; Nelson-Piercy, Catherine; Shoenfeld, Yehuda; Tincani, Angela; Villiger, Peter M; Wallenius, Marianne; von Wolff, Michael
Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.
Mau, W; Beyer, W; Ehlebracht-König, I; Engel, J-M; Genth, E; Jäckel, W H; Lange, U; Thiele, K
Recent Deutsche Gesellschaft für Rheumatologie (DGRh, German Society of Rheumatology) guidelines emphasized the significance of coordinated multidisciplinary care and rehabilitation of patients with inflammatory rheumatic diseases. Nationwide data from the German pension insurance funds showed that inpatient rehabilitation due to rheumatoid arthritis (RA) varied by a factor of 2.6 between the different German states. From 2000 to 2012 rehabilitation measures were reduced by one third, most significantly in men with ankylosing spondylitis (AS). Rehabilitation measures because of RA or AS were provided up to 14 times more frequently by the German statutory pension insurance scheme compared with a large compulsory health insurance which is responsible for rehabilitation measures after retirement. In rehabilitation centers with high numbers of patients with inflammatory rheumatic diseases, higher structural and process quality were demonstrated. In 2011 a total of 40 % of RA patients in the national database of the collaborative arthritis centers showed medium or severe functional limitations. Among these disabled RA patients inpatient rehabilitation was reduced by about 50 % between 1995 and 2011. Out of all RA patients from outpatient rheumatology care with severe functional limitations 38 % had no functional restoration therapy within the previous 12 months with a high variation between rheumatologists. Experiences from other European countries may inspire German rheumatologists and other involved health professionals to initiate a wider range of rehabilitative interventions in the future.
Immunologic laboratory tests serve critical roles in the care of patients with various rheumatic diseases. These tests can provide relevant information of rheumatic diseases based on their immunopathophysiological condition. Although immunologic laboratory tests are quite useful for the determination of diagnosis and the estimation of disease activity, organ involvement and prognosis, they are frequently misused and resulted in an inappropriate diagnosis and treatment. Appropriate use of immunologic laboratory tests and accurate clinical interpretation of the test results can prevent false diagnosis and unnecessary treatment. In order to improve clinical care of patients with rheumatic diseases, clinicians caring patients with rheumatic disease should recognize meanings, characteristics and limitations of each result of immunologic laboratory testing. This article reviewed recent advances in immunologic laboratory testing such as antinuclear antibody, anti-DNA antibody and anti-neutrophil cytoplasmic antibody, and introduced guidelines for these testing. These guidelines based on evidences of EBM may contribute to the appropriate use of immunologic laboratory tests for rheumatic diseases.
Di Franco, Manuela; Lucchino, Bruno; Spaziante, Martina; Iannuccelli, Cristina; Valesini, Guido; Iaiani, Giancarlo
Systemic rheumatic diseases have significant morbidity and mortality, due in large part to concurrent infections. The lung has been reported among the most frequent sites of infection in patients with rheumatic disease, who are susceptible to developing pneumonia sustained both by common pathogens and by opportunistic microorganisms. Patients with rheumatic disease show a peculiar vulnerability to infectious complications. This is due in part to intrinsic disease-related immune dysregulation and in part to the immunosuppressive treatments. Several therapeutic agents have been associated to a wide spectrum of infections, complicating the management of rheumatic diseases. This review discusses the most frequent pulmonary infections encountered in rheumatic diseases, focusing on opportunistic agents, consequent diagnostic challenges and appropriate therapeutic strategies. PMID:28146077
Jendro, M C; Hülsemann, J L; Zeidler, H
HCV-infection is an important infectious disease in rheumatology. It is the cause of mixed cryoglobulinemia and other rheumatic manifestations develop frequently during HCV-infection. These comprise: Sicca-syndrome, thromboembolic events associated with anti-cardiolipin antibodies and fibromyalgia. Also associated with HCV-infection is a non-erosive polyarthritis. This synovitis often fulfills the ACR-criteria for rheumatoid arthritis, but the disease course is different with frequent remissions and non-erosive joint involvement. The following autoantibodies are associated with HCV-infection: Cryoglobulins, rheumatoid factor, antinuclear antibodies (ANA), antismooth muscle antibodies (SMA), anti-phospholipid-antibodies and anti-thyroid-antibodies. In HCV-associated sicca-syndrom, antibodies against Ro (SSA) and La (SSB) are not detected. The course of HCV-infection is often occult, without elevation of liver enzymes. We summarize the clinical and serological signs and symptoms when HCV-infection should be suspected and when HCV-testing should be performed in a rheumatological setting. The identification of HCV-infection in rheumatic patients is important to minimize the risk of aggravating hepatitis by prescription of hepatotoxic drugs and because of the availability of alpha-interferon as a potential virus eradicating agent.
The rheumatic diseases continue to represent a significant healthcare burden in the 21st century. However, despite the best standard of care and recent therapeutic advances it is still not possible to consistently prevent the progressive joint destruction that leads to chronic disability. In rheumatoid arthritis and osteoarthritis this progressive cartilage and bone destruction is considered to be driven by an excess of the matrix metalloproteinase (MMP) enzymes. Consequently, a great number of potent small molecule MMP inhibitors have been examined. Several MMP inhibitors have entered clinical trials as a result of impressive data in animal models, although only one MMP inhibitor, Ro32-3555 (Trocade), a collagenase selective inhibitor, has been fully tested in the clinic, but it did not prevent progression of joint damage in patients with rheumatoid arthritis. The key stages and challenges associated with the development of an MMP inhibitor in the rheumatic diseases are presented below with particular reference to Trocade. It is concluded that the future success of MMP inhibitors necessitates a greater understanding of the joint destructive process and it is hoped that their development may be accompanied with clearer, more practical, outcome measures to test these drugs for, what remains, an unmet medical need. PMID:11890658
Choi, Hyon K.; Nguyen, Uyen-Sa; Niu, Jingbo; Danaei, Goodarz; Zhang, Yuqing
The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias—a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic—in key areas of rheumatic disease research. We present index event bias (a type of selection bias) as one of the potentially unifying reasons behind some unexpected findings, such as the ‘risk factor paradox’—a phenomenon exemplified by the discrepant effects of certain risk factors on the development versus the progression of osteoarthritis (OA) or rheumatoid arthritis (RA). We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research. PMID:24686510
Perandini, Luiz Augusto; de Sá-Pinto, Ana Lúcia; Roschel, Hamilton; Benatti, Fabiana Braga; Lima, Fernanda Rodrigues; Bonfá, Eloisa; Gualano, Bruno
Chronic inflammation is a common feature shared by several autoimmune rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis, and ankylosing spondylitis. Therefore, blocking or reducing inflammation is one of the major treatment strategies in these diseases. In this context, exercise training has emerged as a potential therapeutic tool in counteracting systemic inflammation, thereby leading to better clinical outcomes. The aims of this review are i) to provide a summary of the clinical effects of exercise training in selected autoimmune rheumatic diseases; and ii) to discuss the potential anti-inflammatory role of exercise training in autoimmune rheumatic diseases, stressing the gaps in literature and the clinical and scientific perspectives in the field. Copyright © 2012 Elsevier B.V. All rights reserved.
Guma, Monica; Tiziani, Stefano; Firestein, Gary S
Metabolomics enables the profiling of large numbers of small molecules in cells, tissues and biological fluids. These molecules, which include amino acids, carbohydrates, lipids, nucleotides and their metabolites, can be detected quantitatively. Metabolomic methods, often focused on the information-rich analytical techniques of NMR spectroscopy and mass spectrometry, have potential for early diagnosis, monitoring therapy and defining disease pathogenesis in many therapeutic areas, including rheumatic diseases. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanisms are being revealed and are shaping our understanding of cell biology, physiology and medicine. These pathways can potentially be targeted to diagnose and treat patients with immune-mediated diseases.
Guma, Monica; Tiziani, Stefano; Firestein, Gary S.
Metabolomics enables the profiling of large numbers of small molecules in cells, tissues and biological fluids. These molecules, which include amino acids, carbohydrates, lipids, nucleotides and their metabolites, can be detected quantitatively. Metabolomic methods, often focused on the information-rich analytical techniques of NMR spectroscopy and mass spectrometry, have potential for early diagnosis, monitoring therapy and defining disease pathogenesis in many therapeutic areas, including rheumatic diseases. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanisms are being revealed and are shaping our understanding of cell biology, physiology and medicine. These pathways can potentially be targeted to diagnose and treat patients with immune-mediated diseases. PMID:26935283
Islam, M I; Talukder, M K; Islam, M M; Laila, K; Rahman, S A
Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic disorders, which commonly occurs in systemic juvenile idiopathic arthritis (sJIA).This study was carried out with the aims of describing the clinical features, laboratory findings and outcomes of MAS associated with paediatric rheumatic diseases in the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU) and compare these results with previous studies on MAS. This retrospective study was conducted in the paediatric rheumatology wing of the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Clinical and laboratory profile of all the diagnosed cases of MAS were analyzed from the medical records from January 2010 to July 2015. Among 10 MAS patients, 6 were female and 4 were male. Seven patients of systemic JIA, two patients of SLE and one patient with Kawasaki Disease developed MAS in their course of primary disease. Mean duration of primary disease prior to development of MAS was 2.9 years and mean age of onset was 9.1 years. High continued fever and new onset hepatosplenomegaly were the hallmark of the clinical presentation. White blood cell count and platelet count came down from the mean of 16.2 to 10.2×10⁹/L and 254 to 90×10⁹/L. Mean erythrocyte sedimentation rate was dropped from 56 to 29 mm/hr. Six patients had abnormal liver enzyme level (ALT) and 5 had evidence of coagulopathy (prolonged prothrombin time and APTT) at the onset of disease. Hyperferritinnemia were found in all the patients. Bone marrow study was done in 5 patients but features of hamophagocytosis were found only in 2 patients. All patients received intravenous steroid and 3 patients who did not respond to steroid received additional cyclosporine. Mortality rate was 30% in this series. Macrophage activation syndrome is a fatal complication of paediatric rheumatic diseases among which s-JIA was predominant. Early diagnosis and
Deng, Guo-Min; Kyttaris, Vasileios C.; Tsokos, George C.
Spleen tyrosine kinase (Syk) is a member of the Src family of non-receptor tyrosine kinases, which associates directly with surface receptors, including B-cell receptor and Fcγ receptor, and is involved in a variety of signal transduction pathways. Rheumatoid arthritis (RA) and systemic lupus erythematosus are autoimmune diseases in which autoantibodies, immune complexes, and autoreactive T cells account for the expression of tissue inflammation and damage. Syk inhibitors efficiently suppress RA in patients albeit in the expression of unwanted side effects, including gastrointestinal effects, hypertension, and neutropenia. Syk inhibitors also inhibit clinical manifestations in lupus-prone mice. Here, we review the evidence that supports the use of Syk inhibitors to treat rheumatic and other autoimmune diseases. PMID:27014261
Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael
Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected.
Amezaga Urruela, Matxalen; Suarez-Almazor, Maria E.
Acupuncture has been used for millennia in traditional Chinese medicine as a technique believed to restore the balance of energy in the body caused by disease through the use of needles inserted into specific points or energy channels. This energy is called the De qi. The use of acupuncture for the treatment of pain in musculoskeletal disorders is increasing. Some patients seek alternative therapies because of lack of improvement with conventional treatments. The potential physiological effects of acupuncture on pain relief have been attributed to biochemical processes such as the release of endorphins into the limbic structures, subcortical areas and brain stem, mechanisms that are also present in placebo-induced analgesia. In addition, pain relief with acupuncture is also associated with patient expectations, beliefs and interactions with their acupuncturists. In this review, we summarize the latest evidence on the treatment of musculoskeletal conditions including rheumatoid arthritis, fibromyalgia, neck pain, shoulder pain, low back pain and knee pain with traditional Chinese acupuncture (TCA), electroacupuncture (EA), and the use of moxibustion. Acupuncture is relatively safe but there are still reports of serious and fatal side effects that must be taken into account when recommending this therapy. Many of the latest trials assessing the benefits of acupuncture in rheumatic diseases found that acupuncture was not better than sham acupuncture implying that the analgesic effects observed are related to a strong placebo response. While the literature on this topic is extensive, many of the studies lack methodological rigor, and additional large, well-controlled, high quality trials are still needed to determine if acupuncture might be useful in the treatment of chronic rheumatic diseases. PMID:23055010
Amezaga Urruela, Matxalen; Suarez-Almazor, Maria E
Acupuncture has been used for millennia in traditional Chinese medicine as a technique believed to restore the balance of energy in the body caused by disease through the use of needles inserted into specific points or energy channels. This energy is called the de qi. The use of acupuncture for the treatment of pain in musculoskeletal disorders is increasing. Some patients seek alternative therapies because of lack of improvement with conventional treatments. The potential physiological effects of acupuncture on pain relief have been attributed to biochemical processes, such as the release of endorphins into the limbic structures, subcortical areas and brain stem, mechanisms that are also present in placebo-induced analgesia. In addition, pain relief with acupuncture is also associated with patient expectations, beliefs, and interactions with their acupuncturists. In this review, we summarize the latest evidence on the treatment of musculoskeletal conditions including rheumatoid arthritis, fibromyalgia, neck pain, shoulder pain, low back pain, and knee pain with traditional Chinese acupuncture (TCA), electroacupuncture (EA), and the use of moxibustion. Acupuncture is relatively safe, but there are still reports of serious and fatal side effects that must be taken into account when recommending this therapy. Many of the latest trials assessing the benefits of acupuncture in rheumatic diseases found that acupuncture was not better than sham acupuncture, implying that the analgesic effects observed are related to a strong placebo response. While the literature on this topic is extensive, many of the studies lack methodological rigor, and additional large, well-controlled, high quality trials are still needed to determine if acupuncture might be useful in the treatment of chronic rheumatic diseases.
Ostensen, M; Ramsey-Goldman, R
The interaction of pregnancy and the rheumatic diseases varies, ranging from life-threatening conditions such as thromboembolic events and progressive renal disease in some autoimmune disorders, to minor flares of peripheral arthritis in inflammatory rheumatic disease. As a consequence, treatment strategy will vary according to the maternal or fetal compromise expected. All nonsteroidal anti-inflammatory drugs (NSAIDs), including high dose aspirin (acetylsalicylic acid), can cause adverse effects during pregnancy related to the inhibition of prostaglandin synthesis. Prolongation of gestation and labour, constriction of the ductus arteriosus, persistent fetal circulation, impairment of renal function and bleeding are risks of third trimester exposure of pregnant women to all inhibitors of cyclo-oxygenase. Most of these adverse effects can be prevented by discontinuing NSAIDs 8 weeks prior to delivery. Low dose aspirin has not been associated with fetal or neonatal toxicity. Some corticosteroids such as prednisone and prednisolone do not readily cross the placenta and can be safely used during pregnancy as immunosuppressive drugs. Maternal complications related to corticosteroids may occur and close monitoring is therefore mandatory. There is limited information on the safety of disease-modifying antirheumatic drugs including gold, antimalarials, penicillamine (D-penicillamine), sulfasalazine and cyclosporin. Of these agents, sulfasalazine has the best record for tolerability and can be used by pregnant patients. Gold compounds and penicillamine should be discontinued when pregnancy is recognised. Hydroxychloroquine has not been associated with congenital malformations and seems preferable to chloroquine in patients requiring treatment with antimalarials. Use of cyclosporin may be an alternative to other therapy in pregnant patients with severe rheumatic disease. Indications for treatment with colchicine during pregnancy are few, except for familial Mediterranean
Ostrov, B E
Growth abnormalities are common in pediatric rheumatic diseases. Studies suggest that effects of inflammation such as anorexia, and adipose and muscle tissue breakdown contribute to the nutritional and growth aberrations. The effects of the various cytokines produced during inflammation create a vicious cycle of anorexia and increased catabolism, and may be responsible for the nutritional deficits seen. In future, specific treatment with anticytokine monoclonal antibodies may block these effects, minimizing the nutritional consequences of inflammation.
Richter, Jutta G; Wessel, Ewa; Klimt, Ralf; Willers, Reinhardt; Schneider, Matthias
Early diagnosis of inflammatory rheumatic diseases is important for patients' prognosis and outcome. The mean time delay of 1 to 5 years in Germany between the initial symptoms and the first rheumatologist contact should be reduced. Efficiency of patient questionnaires for the identification of inflammatory rheumatic diseases has been demonstrated in other countries. The aim of our study was to develop a patient questionnaire in German identifying inflammatory rheumatic diseases with a high sensitivity and specificity as well as a high positive predictive value. The RheumaCheck questionnaire was developed by adoption of the FDA-approved Connective Tissue Disease Screening Questionnaire. 1448 patients (195 controls, 437 patients suspicious for and 816 patients with known inflammatory rheumatic diseases) recruited by rheumatologists and general practitioners answered the questionnaire that additionally assessed comorbidities and sociodemographic data. A predictive algorithm was calculated. Mean age of the complete group (73.1% female) was 52.5 +/- 15.1 years. 53.1% had no comorbidity. Application of the algorithm yields a high sensitivity (77.6%) and specificity (79.9%). The area under the ROC curve was 0.85 (p < 0.0001). Being aware of a possible high rate of false true results RheumaCheck is a simple, efficient instrument easily filled out by patients. It can identify the group of patients that needs further investigation, care and assessment by a rheumatologist leading to earlier diagnosis and therapy. A web version of RheumaCheck is provided on www.rheuma-check.de .
Rocha, Beatriz; Cillero-Pastor, Berta; Blanco, Francisco J; Ruiz-Romero, Cristina
Mass spectrometry imaging (MSI) is a technique used to visualize the spatial distribution of biomolecules such as peptides, proteins, lipids or other organic compounds by their molecular masses. Among the different MSI strategies, MALDI-MSI provides a sensitive and label-free approach for imaging of a wide variety of protein or peptide biomarkers from the surface of tissue sections, being currently used in an increasing number of biomedical applications such as biomarker discovery and tissue classification. In the field of rheumatology, MALDI-MSI has been applied to date for the analysis of joint tissues such as synovial membrane or cartilage. This review summarizes the studies and key achievements obtained using MALDI-MSI to increase understanding on rheumatic pathologies and to describe potential diagnostic or prognostic biomarkers of these diseases. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.
Mattukat, K; Thyrolf, A
Rheumatic patients are at risk of social isolation and physical inactivity which can have a significant impact on physical and mental health. Only every seventh patient is organized in a self-help group (SHG), most of them in the German League Against Rheumatism (GLAR). Members of a SHG are socially and physically more active and take part in exercise therapy (ET) more often. Depending on the study, the utilization of ET ranges from 25 % to 71 %. The functional training as the most attended offer of the GLAR showed positive effects at the physical and psychological levels. To motivate difficult to reach patients to engage in self-help and regular exercise, further development of exercise programs with individually tailored intensive strength and endurance elements as well as the increased use of new media seems promising. The Internet provides various opportunities for networking and social participation especially for severely impaired and temporally less flexible patients.
Mariani, Anthea; Marsili, Manuela; Nozzi, Manuela; Faricelli, Raffaella; Chiarelli, Francesco; Breda, Luciana
In most childhood rheumatic diseases, specific diagnostic markers are not yet available. Therefore, a major emphasis in medical research today is directed to the discovery of new inflammation molecules, like calprotectin. Calprotectin (MRP8/MRP14) is a complex of calcium- and zinc-binding proteins that belong to the S100 protein family. This protein is directly released by leukocytes during the interaction with inflammatory activated endothelium at the site of inflammation. Increased plasma calprotectin levels have been found in inflammatory chronic diseases such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel diseases (IBD), multiple sclerosis, cystic fibrosis and systemic lupus erythematosus (SLE). In these diseases, serum calprotectin has been shown to correlate with disease activity and laboratory variables of inflammation such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). This review outlines the validity and the possible applications of calprotectin as a new inflammation marker in paediatric rheumatic diseases.
Navid, Fatemeh; Colbert, Robert A
Rheumatic diseases represent a heterogeneous group of inflammatory conditions, many of which involve chronic activation of both innate and adaptive immune responses by multiple genetic and environmental factors. These immune responses involve the secretion of excessive amounts of cytokines and other signalling mediators by activated immune cells. The endoplasmic reticulum (ER) is the cellular organelle that directs the folding, processing and trafficking of membrane-bound and secreted proteins, including many key components of the immune response. Maintaining homeostasis in the ER is critical to cell function and survival. Consequently, elaborate mechanisms have evolved to sense and respond to ER stress through three main signalling pathways that together comprise the unfolded protein response (UPR). Activation of the UPR can rapidly resolve the accumulation of misfolded proteins, direct permanent changes in the size and function of cells during differentiation, and critically influence the immune response and inflammation. Recognition of the importance of ER stress and UPR signalling pathways in normal and dysregulated immune responses has greatly increased in the past few years. This Review discusses several settings in which ER stress contributes to the pathogenesis of rheumatic diseases and considers some of the therapeutic opportunities that these discoveries provide.
Sinha, Santosh Kumar; Thakur, Ramesh; Krishna, Vinay; Varma, Chandra Mohan; Goel, Amit; Jha, Mukesh Jitendra; Kumar, Ashutosh; Mishra, Vikas; Tiwari, Pradyot; Sinha, Rupesh
Rheumatic disease may involve the pulmonary valve, but is exceedingly rare. Simultaneous involvement of all four valves is more likely to be the result of combination of causes, such as congenital, rheumatic, infective or degenerative disease. A unitary cause for quadrivalvular involvement would be either rheumatic or myxomatous degeneration. A 16-year-old young boy presented with progressive exertional dyspnea for the past 3 years. On evaluation, he was in atrial fibrillation with congestive heart failure. On examination, evidence of stenosis of the mitral, aortic and tricuspid valves with a history of rheumatic fever in childhood was revealed. Transthoracic echocardiography showed the quadrivalvular involvement. Only few reports are available in the literature describing rheumatic quadrivalvar damage and that too in third and fourth decade. This is probably first to be reported in juvenile age group. PMID:28197258
Schoels, Monika M; van der Heijde, Désirée; Breedveld, Ferdinand C; Burmester, Gerd R; Dougados, Maxime; Emery, Paul; Ferraccioli, Gianfranco; Gabay, Cem; Gibofsky, Allan; Gomez-Reino, Juan Jesus; Jones, Graeme; Kvien, Tore K; Murikama, Miho M; Nishimoto, Norihiro; Smolen, Josef S
Background Suppression of the immunoinflammatory cascade by targeting interleukin 6 (IL-6) mediated effects constitutes a therapeutic option for chronic inflammatory diseases. Tocilizumab is the only IL-6 inhibitor (IL-6i) licensed for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), but also other agents targeting either IL-6 or its receptor are investigated in various indications. Objective To review published evidence on safety and efficacy of IL-6i in inflammatory diseases. Methods We performed systematic literature searches in Medline and Cochrane, screened EULAR and American College of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials.gov. Results Comprehensive evidence supports the efficacy of tocilizumab in RA in DMARD-naïve patients, and after DMARD- and TNFi-failure. Randomised comparisons demonstrate superiority of tocilizumab in JIA, but not ankylosing spondylitis (AS). Other indications are currently investigated. Additional IL-6i show similar efficacy; safety generally appears acceptable. Conclusions IL-6i is effective and safe in RA and JIA, but not in AS. Preliminary results in other indications need substantiation. PMID:23144446
Ciechomska, Marzena; O'Reilly, Steven
Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases.
Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases. PMID:27594771
Grover, A.; Dhawan, A.; Iyengar, S. D.; Anand, I. S.; Wahi, P. L.; Ganguly, N. K.
The epidemiology of rheumatic fever and rheumatic heart disease in a rural community (total population 114,610) in northern India was studied by setting up a registry based on primary health care centres. Health workers and schoolteachers were trained to identify suspected patients in school and village surveys (121 villages). Medical specialists screened 5-15-year-olds (n = 31,200). The population was followed up for 3 years (from March 1988 to March 1991). All suspected and registered cases were investigated by serial echocardiography and Doppler ultrasonography at a tertiary care centre. A total of 102 cases were confirmed to have rheumatic fever/rheumatic heart disease (prevalence, 0.09%); 66 were aged 5-15 years (prevalence, 0.21%). A total of 48 patients (24 males, 24 females; mean age, 12.11 +/- 3.7 years) were diagnosed to have a possible first attack of rheumatic fever (incidence, 0.54 per 1000 per year). Arthritis was observed in 36 (75%) and carditis in 18 (37.5%) of cases. Prolapse of the anterior mitral leaflet into the left atrium occurred in 5 (22%) cases with carditis. Mitral regurgitation was observed in all 18 cases of carditis; over the period of observation it disappeared in three cases and progressed to mitral stenosis in a further three. A total of 22 patients (11 males, 11 females; mean age, 19.41 +/- 8.1 years) were registered as rheumatic fever recurrences, and 32 patients (18 females, 14 males; mean age, 22.1 +/- 10.1 years) had chronic rheumatic heart disease. Of those with recurrences, 9 (41%) had carditis and 11 (50%) had arthritis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8440039
Douglas, K M J; Ladoyanni, E; Treharne, G J; Hale, E D; Erb, N; Kitas, G D
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
Wang, Yu-Jie; Huang, Xiao-Lei; Yan, Jun-Wei; Wan, Ya-Nan; Wang, Bing-Xiang; Tao, Jin-Hui; Chen, Bing; Li, Bao-Zhu; Yang, Guo-Jun; Wang, Jing
Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of "vascular", "neural" and "intravascular". Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.
Joosten, Leo A B; Abdollahi-Roodsaz, Shahla; Dinarello, Charles A; O'Neill, Luke; Netea, Mihai G
In the past few years, new developments have been reported on the role of Toll-like receptors (TLRs) in chronic inflammation in rheumatic diseases. The inhibitory function of TLR10 has been demonstrated. Receptors that enhance the function of TLRs, and several TLR inhibitors, have been identified. In addition, the role of the microbiome and TLRs in the onset of rheumatic diseases has been reported. We review novel insights on the role of TLRs in several inflammatory joint diseases, including rheumatoid arthritis, systemic lupus erythematosus, gout and Lyme arthritis, with a focus on the signalling mechanisms mediated by the Toll-IL-1 receptor (TIR) domain, the exogenous and endogenous ligands of TLRs, and the current and future therapeutic strategies to target TLR signalling in rheumatic diseases.
Henderson, C J; Panush, R S
Rheumatoid arthritis and many other systemic rheumatic diseases remain illnesses of unknown cause for which current therapy is often inadequate. This leads patients to seek questionable remedies, prominent among which are dietary manipulations. Is there a role for dietary modifications in the routine therapy for patients with rheumatic diseases? This article discusses the relationships between diets, fasting, elemental nutrition, vitamins, minerals, and foods for rheumatic diseases. Known scientific-based evidence for the use, safety, and efficacy of diets and dietary-related practices subscribed by patients with rheumatic diseases are presented. Studies that link diet with arthritis offer the possibility of identifying new therapeutic approaches for selected patients and of developing new insights to disease pathogenesis. Dietary therapy for arthritis, however, is still being investigated.
Cappelli, Laura C; Shah, Ami A; Bingham, Clifton O
Immune checkpoint inhibitors (ICIs) are newly approved treatments for advanced malignancies that are increasing survival. The mechanism of these drugs, non-specifically activating T cells, also leads to immune-mediated damage of tissue or immune-related adverse events (IRAE). IRAEs with rheumatic phenotypes are increasingly being recognised. Inflammatory arthritis, sicca syndrome, inflammatory myopathy, vasculitis and lupus nephritis have been described as a result of ICIs. Use of ICIs will be expanding in the coming years for several reasons. ICIs will be used in earlier stage cancer, for more indications, and additional drugs will be approved. The rheumatologist plays a critical role in evaluating and treating these patients. The expertise of rheumatologists in evaluating rheumatic signs and symptoms and treating patients with immunosuppression are critical in ensuring the optimal outcomes for patients with rheumatic IRAE. Collaboration between oncology and rheumatology for clinical care and research will enhance understanding of these new disease entities.
Cappelli, Laura C; Shah, Ami A; Bingham, Clifton O
Immune checkpoint inhibitors (ICIs) are newly approved treatments for advanced malignancies that are increasing survival. The mechanism of these drugs, non-specifically activating T cells, also leads to immune-mediated damage of tissue or immune-related adverse events (IRAE). IRAEs with rheumatic phenotypes are increasingly being recognised. Inflammatory arthritis, sicca syndrome, inflammatory myopathy, vasculitis and lupus nephritis have been described as a result of ICIs. Use of ICIs will be expanding in the coming years for several reasons. ICIs will be used in earlier stage cancer, for more indications, and additional drugs will be approved. The rheumatologist plays a critical role in evaluating and treating these patients. The expertise of rheumatologists in evaluating rheumatic signs and symptoms and treating patients with immunosuppression are critical in ensuring the optimal outcomes for patients with rheumatic IRAE. Collaboration between oncology and rheumatology for clinical care and research will enhance understanding of these new disease entities. PMID:27752360
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Rheumatic illnesses are a common cause for musculoskeletal complaints in the general population. All ages can be affected, including people in the prime of their working years. Secondary problems, such as entrapment neuropathies, enthesopathies, and Raynaud's syndrome, can be associated with various inflammatory arthritides. A detailed history and physical are the most important tools in screening for potential inflammatory disease in workers with upper extremity complaints.
Østensen, Monika; Förger, Frauke; Villiger, Peter M
Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy-related disorders. Studies at the level of the maternal-fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study.
Rush, Catherine M.; Govan, Brenda L.; Sikder, Suchandan; Williams, Natasha L.; Ketheesan, Natkunam
Rheumatic fever (RF) and rheumatic heart disease (RHD) are sequelae of group A streptococcal (GAS) infection. Although an autoimmune process has long been considered to be responsible for the initiation of RF/RHD, it is only in the last few decades that the mechanisms involved in the pathogenesis of the inflammatory condition have been unraveled partly due to experimentation on animal models. RF/RHD is a uniquely human condition and modeling this disease in animals is challenging. Antibody and T cell responses to recombinant GAS M protein (rM) and the subsequent interactions with cardiac tissue have been predominantly investigated using a rat autoimmune valvulitis model. In Lewis rats immunized with rM, the development of hallmark histological features akin to RF/RHD, both in the myocardial and in valvular tissue have been reported, with the generation of heart tissue cross-reactive antibodies and T cells. Recently, a Lewis rat model of Sydenham’s chorea and related neuropsychiatric disorders has also been described. Rodent models are very useful for assessing disease mechanisms due to the availability of reagents to precisely determine sequential events following infection with GAS or post-challenge with specific proteins and or carbohydrate preparations from GAS. However, studies of cardiac function are more problematic in such models. In this review, a historical overview of animal models previously used and those that are currently available will be discussed in terms of their usefulness in modeling different aspects of the disease process. Ultimately, cardiologists, microbiologists, immunologists, and physiologists may have to resort to diverse models to investigate different aspects of RF/RHD. PMID:25414841
Lionetti, Geraldina; Kimura, Yukiko; Schanberg, Laura E; Beukelman, Timothy; Wallace, Carol A; Ilowite, Norman T; Winsor, Jane; Fox, Kathleen; Natter, Marc; Sundy, John S; Brodsky, Eric; Curtis, Jeffrey R; Del Gaizo, Vincent; Iyasu, Solomon; Jahreis, Angelika; Meeker-O'Connell, Ann; Mittleman, Barbara B; Murphy, Bernard M; Peterson, Eric D; Raymond, Sandra C; Setoguchi, Soko; Siegel, Jeffrey N; Sobel, Rachel E; Solomon, Daniel; Southwood, Taunton R; Vesely, Richard; White, Patience H; Wulffraat, Nico M; Sandborg, Christy I
The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short- and long-term complications such as infection and malignancy. These complications are especially worrisome in children who often have serial exposures to multiple immunomodulatory products. Post-marketing surveillance of immunomodulatory products in juvenile idiopathic arthritis (JIA) and pediatric systemic lupus erythematosus is currently based on product-specific registries and passive surveillance, which may not accurately reflect the safety risks for children owing to low numbers, poor long-term retention, and inadequate comparators. In collaboration with the US Food and Drug Administration (FDA), patient and family advocacy groups, biopharmaceutical industry representatives and other stakeholders, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the Duke Clinical Research Institute (DCRI) have developed a novel pharmacosurveillance model (CARRA Consolidated Safety Registry [CoRe]) based on a multicenter longitudinal pediatric rheumatic diseases registry with over 8000 participants. The existing CARRA infrastructure provides access to much larger numbers of subjects than is feasible in single-product registries. Enrollment regardless of medication exposure allows more accurate detection and evaluation of safety signals. Flexibility built into the model allows the addition of specific data elements and safety outcomes, and designation of appropriate disease comparator groups relevant to each product, fulfilling post-marketing requirements and commitments. The proposed model can be applied to other pediatric and adult diseases, potentially transforming the paradigm of pharmacosurveillance in response to the growing public mandate for rigorous post-marketing safety monitoring.
Lionetti, Geraldina; Kimura, Yukiko; Schanberg, Laura E.; Beukelman, Timothy; Wallace, Carol A.; Ilowite, Norman T.; Winsor, Jane; Fox, Kathleen; Natter, Marc; Sundy, John S.; Brodsky, Eric; Curtis, Jeffrey R.; Del Gaizo, Vincent; Iyasu, Solomon; Jahreis, Angelika; Meeker-O’Connell, Ann; Mittleman, Barbara B.; Murphy, Bernard M.; Peterson, Eric D.; Raymond, Sandra C.; Setoguchi, Soko; Siegel, Jeffrey N.; Sobel, Rachel E.; Solomon, Daniel; Southwood, Taunton R.; Vesely, Richard; White, Patience H.; Wulffraat, Nico M.; Sandborg, Christy I.
The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short- and long-term complications such as infection and malignancy. These complications are especially worrisome in children who often have serial exposures to multiple immunomodulatory products. Post-marketing surveillance of immunomodulatory products in juvenile idiopathic arthritis (JIA) and pediatric systemic lupus erythematosus is currently based on product-specific registries and passive surveillance, which may not accurately reflect the safety risks for children owing to low numbers, poor long-term retention, and inadequate comparators. In collaboration with the US Food and Drug Administration (FDA), patient and family advocacy groups, biopharmaceutical industry representatives and other stakeholders, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the Duke Clinical Research Institute (DCRI) have developed a novel pharmacosurveillance model (CARRA Consolidated Safety Registry [CoRe]) based on a multicenter longitudinal pediatric rheumatic diseases registry with over 8000 participants. The existing CARRA infrastructure provides access to much larger numbers of subjects than is feasible in single-product registries. Enrollment regardless of medication exposure allows more accurate detection and evaluation of safety signals. Flexibility built into the model allows the addition of specific data elements and safety outcomes, and designation of appropriate disease comparator groups relevant to each product, fulfilling post-marketing requirements and commitments. The proposed model can be applied to other pediatric and adult diseases, potentially transforming the paradigm of pharmacosurveillance in response to the growing public mandate for rigorous post-marketing safety monitoring. PMID:24144710
Kino, Tomoshige; Charmandari, Evangelia; Chrousos, George P.
The glucocorticoid receptor (GR), a member of the nuclear receptor superfamily, mediates most of the known biologic effects of glucocorticoids. The human GR gene consists of 9 exons and expresses 2 alternative splicing isoforms, the GRα and GRβ. GRα is the classic receptor that binds to glucocorticoids and mediates most of the known actions of glucocorticoids, while GRβ does not bind to these hormones and exerts a dominant negative effect upon the GRα-induced transcriptional activity. Each of the two GR splice isoforms has 8 translational variants with specific transcriptional activity and tissue distribution. GRα consists of three subdomains, translocates from the cytoplasm into the nucleus upon binding to glucocorticoids, and regulates the transcriptional activity of numerous glucocorticoid-responsive genes either by binding to its cognate DNA sequences or by interacting with other transcription factors. In addition to these genomic actions, the GR also exerts rapid, non-genomic effects, which are possibly mediated by membrane-localized receptors or by translocation into the mitochondria. All these actions of the GR appear to play an important role in the regulation of the immune system. Specifically, the splicing variant GRβ may be involved in the pathogenesis of rheumatic diseases, while the circadian regulation of the GR activity via acetylation by the Clock transcription factor may have therapeutic implications for the preferential timing of glucocorticoid administration in autoimmune inflammatory disorders. PMID:22018181
Bermas, Bonnie L
To review the recent literature on the safety of nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids and traditional disease-modifying antirheumatic drugs before and during pregnancy. Recent data suggest that the risk of cleft palate formation after in-utero glucocorticoid exposure is lower than previously reported. Two studies of inadvertent leflunomide exposure during early pregnancy suggest that this medication may be less teratogenic than previously thought. Although NSAIDs are well tolerated for use during the first two trimesters of pregnancy, they should be avoided during a conception cycle so as not to impede implantation. After gestational week 30, these medications should be discontinued as they may cause premature closure of the ductus arteriosus. The nonfluorinated glucocorticoids, prednisone and prednisolone, can be used throughout pregnancy, although use during the first trimester may increase the risk of cleft palate formation. Protracted glucocorticoids exposure during pregnancy can cause maternal preterm premature rupture of the membranes, gestational hypertension and gestational diabetes. Methotrexate and leflunomide are teratogenic and should be avoided during pregnancy. The immunosuppressive agents, azathioprine, 6-mercaptopurine and cyclosporine A, are compatible with pregnancy.
Zühlke, Liesl J; Engel, Mark E; Remenyi, Bo; Wyber, Rosemary; Carapetis, Jonathan
The second rheumatic heart disease (RHD) forum was held on February 18, 2013, at the Sixth World Congress of Pediatric Cardiology and Cardiac Surgery in Cape Town, South Africa, to focus attention on key areas in global RHD control, management, and prevention. Building on the foundation of the first RHD forum, over 150 interested participants met to discuss critical issues on the RHD landscape. Unique to this meeting was a mixture of diverse backgrounds and disciplines, all crucially important to the conversation around RHD control and prevention. Some clear priorities have emerged for RHD activities in the next era: the necessity for political intervention and policy change; increasing the health workforce by incorporating teaching, training, and task-shifting; revitalizing the research agenda by merging basic, clinical, and translational research; and obtaining universal access to high-quality penicillin. There was also an urgent request for new resources; for existing resources to be further developed, improved, and shared across platforms; and for resources to be supported in the nonmedical arena. Finally, the necessity of involving the patient community in the ongoing discussion was highlighted. The participants of both the first and second RHD forum represent a new, thriving, and growing community of RHD activists who should usher in a new era of significant improvements in RHD control and prevention. Copyright © 2013 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.
McNeal, R L
Aquatic therapy is justifiably a rapidly expanding, beneficial form of patient treatment. The goals established at the initial and subsequent evaluations usually are met as quickly and as sensibly as possible. Understanding the theory of water techniques is essential in implementing an aquatic therapy program. The success of the program, however, will always depend on the pleasure and benefits achieved by the patients. Remember, rheumatic patients most likely will need to modify their previous daily functioning. Patients need to be aware of the long-term ramifications of the disease process and understand how treatment and care may be altered during various stages of exacerbation and remission. Patient education is critical in ensuring individual responsibility for the changes that must be made when not supervised by a professional. Aquatic therapy is a step in molding a positive lifestyle change for the patient. The patient can be encouraged to be fitness oriented and, at the same time, exercise in a manner that is safe, effective, and biomechanically and physiologically sound. The environment, hopefully, also will be conductive to family and social interaction that ultimately encourages the compliance of long-term exercise programs.
Detert, J; Pischon, N; Burmester, G-R; Buttgereit, F
Inflammatory periodontal disease (PD) is a common disease worldwide that has a primarily bacterial aetiology and is characterized by dysregulation of the host inflammatory response. The degree of inflammation varies among individuals with PD independently of the degree of bacterial infection, suggesting that alteration of the immune function may substantially contribute to its extent. Factors such as smoking, education, and body mass index (BMI) are discussed as potential risk factors for PD. Most PD patients respond to bacterial invaders by mobilizing their defensive cells and releasing cytokines such as interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, and IL-6, which ultimately causes tissue destruction by stimulating the production of collagenolytic enzymes, such matrix metalloproteinases. Recently, there has been growing evidence suggesting an association between PD and the increased risk of systemic diseases, such ateriosclerosis, diabetes mellitus, stroke, and rheumatoid arthritis (RA). PD and rheumatologic diseases such as RA share many pathological aspects and immunological findings.
Tyndall, A; Steiger, U
A red or painful eye may be the clue to a systemic condition, many of which are of a rheumatological or immunological nature. Conjunctivitis may occur in Sjögren's Syndrome, Reiter's Syndrome (and other sero negative spondyloarthropathies) and with infections such as chlamydia and viruses. 70% of cases of episcleritis are idiopathic, the other 30% being associated with rheumatoid arthritis or other connective tissue diseases or herpes zoster infection. Scleritis may be seen with connective tissue diseases or auto immune conditions (rheumatoid arthritis, Wegener granulomatosis, polyarteritis nodosa, relapsing polychondritis, SLE), infections (herpes, tuberculosis, syphilis, aspergillosis) or metabolic (gout, porphyria, cystinosis). Retinal vasculitis is seen in SLE, Behçet's Disease, sarcoidosis, polyarteritis nodosa, Whipple's disease and Crohn's disease among others. However, uveitis presents perhaps the greatest diagnostic challenge and interface between ophthalmology and rheumatology. Some syndromes are purely ophthalmological (eg: Fuch's heterochromic cyclitis) but others may lead to the diagnosis of a rheumatic disorder (eg: recurrent unilateral acute anterior uveitis and ankylosing spondylitis). Systemic syndromes most likely to be associated with uveitis are Reiter's disease, ankylosing spondylitis, sarcoidosis, juvenile arthritis, interstitial nephritis, inflammatory bowel disease, syphilis. The patterns are different, eg: acute painful unilateral anterior uveitis with ankylosing spondylitis and chronic asymptomatic bilateral uveitis in juvenile arthritis (ANA positive, pauci-articular) or bilateral symptomatic uveitis in sarcoidosis. An illustrative case will be presented and an algorithm for the evaluation of uveitis discussed.
The development of biologic drugs has undoubtedly enhanced the spectrum of treatments available for immune-mediated inflammatory rheumatic diseases such as rheumatoid arthritis. However, despite their clear clinical benifits, use of biologics is often hindered by their high costs. The manufacture and subsequent approval of more cost-effective 'biosimilar' versions of these drugs may address this issue and improve patient access. CT-P13 (Remsima(®), Inflectra(®)), a biosimilar of infliximab (Remicade(®)), has shown comparable efficacy, safety and pharmacokinetics to its originator drug in clinical studies. The articles in this supplement present a scientific update on the development and use of biosimilars in rheumatic disorders, with specific focus on CT-P13. The information discussed highlights the predicted positive clinical and economic impact of biosimilars on the management of rheumatic diseases.
Palazzi, Carlo; Buskila, Dan; D'Angelo, Salvatore; D'Amico, Emilio; Olivieri, Ignazio
Hepatitis C virus infection (HCV) is one of the best mimes in medicine. About 40-70% of patients suffering from this disorder develop at least one extra-hepatic disorder that can have a rheumatic nature (arthralgias, arthritis, vasculitis and sicca syndrome) and must be differentiated from the primitive rheumatic diseases. In addition, HCV infection can also alter the laboratory tests. Several alterations of first line laboratory tests can be usually found in both chronic HCV infection and chronic inflammatory rheumatic disorders. In the present review we analyze the interference of HCV in tests more specifically used in rheumatology: rheumatoid factor and other autoantibodies (ANA, anti-ENA, ANCA, anti-DNA, antiphospholipid, anti-CCP). In patients suffering from HCV infection, the diagnosis of connective tissue diseases (CTD) or rheumatoid arthritis (RA) should be made only when the detected symptoms or laboratory data are not inducible by HCV, otherwise only a diagnosis of "possible CTD" or "possible RA" should be considered.
Hung, L C; Nadia, R
A total of 39 titles related to rheumatic fever or rheumatic heart disease in Malaysia were found with online literature search dating back to their inceptions and through 2014. Additional publications from conference journals were included. Nine papers were selected based on clinical relevance and future research implications. There were no population-based studies on the incidence or prevalence of ARF or RHD. In the 1980s, the incidence of admission due to ARF ranged from 2 to 21.1 per 100 000 paediatric admission per year. The burden of disease was significant in the adult population; 74.5% of patients with RHD were female, of which 77.1% were in the reproductive age group of 15-45 years old. Rheumatic mitral valve disease constituted almost half (46.7%) of all mitral valve repairs, ranging from 44.8 - 55.8 patients per year from 1997 - 2003. From 2010-2012, mitral valve interventions increased to 184 per year, of which 85.7% were mitral valve repair. In children with ARF, 25.4% - 41.7% had past history of rheumatic fever or RHD. In patients with rheumatic mitral valve disease undergoing surgical or medical interventions, only 6% reported history of ARF, none had history of GABHS pharyngitis or antibiotic prophylaxis. Only 44.7% of patients with RHD on follow-up were on intramuscular benzathine penicillin prophylaxis. Overall, there is scarcity of publications on ARF and RHD in Malaysia. Priority areas for research include determination of the incidence and prevalence of ARF and RHD, identification of high-risk populations, evaluation on the implementation and adherence of secondary preventive measures, identification of subclinical RHD especially amongst the high-risk population, and a surveillance system to monitor and evaluate preventive measures, disease progression and outcomes.
Jhinghan, B; Mehra, N K; Reddy, K S; Taneja, V; Vaidya, M C; Bhatia, M L
The distribution of HLA-A, -B and -DR antigens as well as blood groups and secretor status was studied in sporadic, North Indian patients of rheumatic fever and rheumatic heart disease. While HLA-Aw33 occurred with an increased frequency in the patient group (X2 = 4.01), no statistically significant differences were observed in the frequency of B-locus antigens. In the DR locus, HLA-DR3 was found to be significantly increased (50% vs 26.1%, X2 = 13.8) and DR2 significantly reduced (21.8% vs 47.0%, X2 = 15.6). Also, there was a preponderance of non-'O' blood group individuals in the patient group as compared to controls. The DR3 association was significant only in those patients of RHD who did not have any previous history of rheumatic fever. These results indicate that susceptibility to rheumatic heart disease is HLA-class II mediated, with HLA-DR3 influencing susceptibility and DR2 conferring protection.
Nowakowska-Płaza, Anna; Pracoń, Grzegorz; Sudoł-Szopińska, Iwona
In the past years, ultrasound imaging has become an integral element of the diagnostic process in rheumatic diseases. It enables the identification of a range of inflammatory changes in joint cavities, sheaths and bursae, and allows their activity to be assessed. In 2012, experts of the European Society of Musculoskeletal Radiology prepared recommendations concerning the role of ultrasonography in the diagnosis of musculoskeletal diseases. Ultrasound was considered the method of choice in imaging peripheral synovitis. Moreover, ultrasound imaging has been popularized thanks to the new classification criteria for rheumatoid arthritis issued by the American College of Rheumatology and European League Against Rheumatism in 2010. They underline the role of ultrasound imaging in the detection of articular inflammatory changes that are difficult to assess unambiguously in the clinical examination. These criteria have become the basis for recommendations prepared by experts from the European League Against Rheumatism concerning medical imaging in rheumatoid arthritis. Nine of ten recommendations concern ultrasonography which is relevant in detecting diseases, predicting their progression and treatment response, monitoring disease activity and identifying remission. In the new criteria concerning polymyalgia rheumatica from 2012, an ultrasound scan of the shoulder and pelvic girdle was considered an alternative to clinical assessment. Moreover, the relevance of ultrasonography in the diagnosis and monitoring of peripheral spondyloarthropathies was widely discussed in 2014 during the meeting of the European League Against Rheumatism in Paris. PMID:27104003
Pereira, Vanessa Patricia L; Robazzi, Teresa Cristina Martins Vicente
Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents. Copyright © 2016. Published by Elsevier Editora Ltda.
Pereira, Vanessa Patricia L; Robazzi, Teresa Cristina Martins Vicente
Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.
Leão, Sydney Correia; Lima, Maria Regina Menezes; do Nascimento, Hertaline Menezes; Octacilio-Silva, Shirlei; Rodrigues, Tania Maria de Andrade
Objective To evaluate the immunological profile and gene expression of endothelin-1 (ET-1) in mitral valves of patients with rheumatic fever originated from a reference service in cardiovascular surgery. Methods This was a quantitative, observational and cross-sectional study. Thirty-five subjects (divided into four groups) participated in the study, 25 patients with chronic rheumatic heart disease and ten control subjects. The mean age of the sample studied was 34.5 years. Seventeen of them (48.58%) were male and 18 (51.42%) were female. Inflammatory cytokines (TNF-α, IL-4 and IL-10) were measured and ten mitral valves of patients who underwent first valve replacement were collected for determination of gene expression of endothelin-1 by real time PCR. Results Among the groups studied (patients vs. controls), there was a statistically significant difference in IL-10 levels (P=0.002), and no differences in other cytokines. Expression of endothelin-1 was observed in 70% of samples. Quantitatively, average of ET-1 expression was 62.85±25.63%. Conclusion Inflammatory cytokine IL-10 participates in the maintenance of chronicity of rheumatic fever in patients who underwent valve replacement and those who are undergoing medical treatment. The expression of endothelin-1 in heart valve lesions in patients undergoing mitral valve replacement confirms its association with inflammatory activity in rheumatic fever. PMID:24896159
The persistence of acute rheumatic fever continues to be seen globally. Once thought to be eradicated in various parts of the world, the disease came back with a vengeance secondary to a lack of diligence on the part of providers. Today, the global burden of group A streptococcal infection, the culprit of the numerous sequelae manifested in acute rheumatic fever, is considerable. Although a completely preventable disease, rheumatic fever continues to exist. It is a devastating disease that involves long-term, multisystem treatment and monitoring for patients who were unsuccessful at eradicating the precipitating group A streptococcal infection. Prevention is the key to resolving the dilemma of the disease's global burden, yet the method to yield its prevention still remains unknown. Thus, meticulous attention to implementing proper treatment is the mainstay and remains a top priority.
Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong
This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.
Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong
This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE. PMID:28273146
Neville, Autumn; Bernatsky, Sasha; Kuriya, Bindee; Bujold, Emmanuel; Chakravarty, Eliza; Platt, Robert W; Bérard, Anick; Vinet, Évelyne
This conference report describes six presentations that were given during a Canadian Institutes for Health Research-funded workshop. The goal of the workshop was to discuss key knowledge gaps in the study of outcomes in mothers with rheumatic diseases and their offspring. Presentations focused on epidemiological and methodological issues associated with the reproductive and perinatal health of women with rheumatic diseases. Discussions of relevant recent research allowed for discovery of potential data sources that could facilitate interdisciplinary research and created the opportunity for future collaborations.
The National Data Bank for Rheumatic Diseases (NDB) is a longitudinal observational patient-driven database, founded as a non-profit research organization in 1998 by Dr. Frederick Wolfe. Patients are sent a primary questionnaire twice a year. More than 50,000 patients with more than 100 various rheumatic diseases under the care of more than 1,500 rheumatologists have completed at least one 6-month questionnaire. Many important publications concerning rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, fibromyalgia, and pharmaco-epidemiology have resulted from NDB research.
Helland, Ylva; Kjeken, Ingvild; Steen, Eldri; Kvien, Tore K; Hauge, Mona-Iren; Dagfinrud, Hanne
To explore how intimate relationships and sexuality are influenced by rheumatic diseases and to describe self-management strategies used to manage disease consequences. To ensure that data were grounded in patients' language and experiences, individual and focus group interviews were conducted. Purposeful sampling was used to ensure variation in age, sex, disease duration, diagnosis, and marital status among the informants. Participants were men and women ages 18 years or older, were diagnosed with inflammatory rheumatic disease by a rheumatologist, and had a disease duration of ≥2 years. The mean age of the 23 participants was 44 years, the mean disease duration was 13.6 years, and the mean ± SD modified Health Assessment Questionnaire score was 1.58 ± 0.46. Four key themes summarized the main issues described by the informants: between disease and normality, relational aspects, disease-related sexual challenges, and self-management strategies. The results reveal that the disease constituted a disruption in life, requiring a new orientation of sexual identity and relationship. Participants' experiences of sexuality went beyond specific sexual activity, including aspects such as body image and relational issues, illustrating a multidimensional perception of sexuality. A large inter- and intrapersonal variety of impact and a wide range of management strategies were reported. This study shows that sexuality is a vital area of life for people living with arthritis. It is a source of physical pleasure and intimacy with their partner, but may cause anxiety and distress when affected by rheumatic disease. However, various self-management strategies are applied to enhance intimate relationships and sexual activity. Knowledge and openness concerning sexual issues need to be emphasized as part of the competence of health professionals and researchers. Copyright © 2011 by the American College of Rheumatology.
Cutolo, Maurizio; Pizzorni, Carmen; Sulli, Alberto
Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels. Copyright © 2011 Elsevier B.V. All rights reserved.
Stoll, Matthew L; Cron, Randy Q
There has been increasing interest in the contents and function of the microbiota, as it relates to pediatric inflammatory diseases. Here, we discuss the factors underlying the development of the microbiota, its role in juvenile idiopathic arthritis (JIA) and prospects for therapeutic interventions in the microbiota. The human microbiota undergoes a succession of changes, until it reaches a mature form. A variety of early-life exposures, including mode of delivery and form of feeding, can affect the contents of the microbiota and possibly impact upon long-term risk of developing autoimmune diseases. The microbiota is altered in children with JIA, including elevated Bacteroides genus in JIA as a whole and decreased Faecalibacterium prausnitzii in pediatric spondyloarthritis. Although there are limited data so far indicating that microbiota-based therapies can result in therapeutic improvement of arthritis, most of the data are on adults and thus may not be applicable to children. Perturbations of the microbiota during childhood may result in the development of a microbiota associated with increased risk of pediatric rheumatic illness. Whether the microbiota can be targeted is a focus of ongoing research.
Rheumatic fever continues unabated among the indigenous Māori and Pacific Island New Zealanders. Ethnic disparities have increased in the past decade. The major success story for disease control has been secondary penicillin prophylaxis with 28-day intramuscular benzathine penicillin with high penicillin delivery rates and low recurrence rates. A landmark study for primary prevention of acute rheumatic fever for group A streptococcal pharyngitis was published in 2009. New Zealand has helped establish the role of echocardiography in acute rheumatic fever, with subclinical carditis incorporated into guidelines as a major criterion of rheumatic fever in high prevalence regions. The rates of mitral valve repair for rheumatic heart disease (RHD) are currently greater than 90% in the children's cardiac unit but remain low in adult cardiac units in New Zealand. This is particularly relevant to women of child bearing age where New Zealand data has shown that pregnancy outcomes for mothers with prosthetic valves on warfarin are poor. There are new initiatives to prevent severe RHD using portable echocardiography by screening school aged children. The prevalence of definite RHD was 2.4% in a large cohort of socially disadvantaged children in South Auckland studied in 2007-2008. Cost benefit models of screening need to be developed. Ongoing research involves international consensus standardisation of RHD patterns, and the need to define the natural history of subclinical RHD.
Buras, Aleksandra; Waszkiewicz, Napoleon; Szulc, Agata
It is known that the prevalence of depression in rheumatologic patients is higher than in the general population. Socioeconomic factors are not a sufficient explanation of mood disorder in these patients. Symptoms reported by patients with chronic inflammatory diseases resemble changes defined as "sickness behavior". Mood disorders among somatic patients could be explained by disturbances of the immune system according to the monoaminergic theory of depression. Inflammatory factors such as IL-1 (interleukin-1), IL-2 (interleukin-2), IL-6 (interleukin-6), TNF-α (tumor necrosis factor α), and IFN-γ (interferon-γ) act within the CNS (central nervous system). They get through from peripheral tissues as well as being synthesized de novo by neurons. This cytokine activity correlates positively with depression intensity as well as with genetic polymorphism of the serotonin (5-HT) transporter. The theory of glucocorticoid resistance-mediated depression (limbic-hypothalamic-pituitary-adrenal [LHPA] axis) is also connected with gained proinflammatory cytokines activity. It might assume the form of a vicious circle. Depressed mood is probably linked with depression in immune-mediated diseases. An elevated level of proinflammatory cytokines is able to activate IDO (indoleamine 2,3-dioxygenase)--an enzyme catabolizing tryptophan (5-HT precursor). Those reactions probably play the main role at the biochemical level. IDO metabolites extensively disturb neurotransmission. 3-Hydroxykynurenine (3OH-KYN), quinolinic acid (Quin) and kynurenic acid (KYNA) are neurotoxic by releasing oxidative stress mediators. Moreover, they activate MAO (monoamine oxidase), which degrades neurotransmitters responsible for stable mood. Bidirectional communication between the neuroendocrine and immune systems is significant for depression treatment, as well as CNS protection against incremental neurodegeneration among seemingly diverse diseases.
Mavrogeni, Sophie; Markousis-Mavrogenis, George; Kolovou, Genovefa
Factors leading to Cardiovascular Disease (CVD) in Autoimmune Rheumatic Diseases (ARD) include: a) atherosclerosis and macro-microvascular coronary artery disease b) pericardial, myocardial and vascular inflammation c) heart valve disease d) heart failure and e) pulmonary hypertension.Cardiology utilizes various non-invasive imaging modalities, such as rest/stress Electrocardiogram (ECG), echocardiography, nuclear imaging and more recently Cardiovascular Magnetic Resonance (CMR) to detect ischemic or inflammatory disease in ARD. Exercise ECG is a reliable prognostic test for identification of patients either very unlikely or very likely to have cardiac events. However, this is not the case for intermediate risk patients. In stress echocardiography the diagnostic end point for the detection of myocardial ischemia is the induction of a transient worsening in regional function during stress. It provides similar diagnostic and prognostic accuracy as radionuclide stress perfusion, but at a lower cost and without radiation exposure. Stress Myocardial Perfusion Scintigraphy (MPS) is a non-invasive imaging modality for patients with suspected coronary artery disease, but has important limitations including radiation exposure, imaging artefacts and low spatial resolution, which preclude detection of small myocardial scars commonly found in ARD. By identifying early stages of inflammation and perfusion defects, CMR can shed light on the exact pathophysiologic background of myocardial lesions, even if the underlying ARD seems stable. However, high cost and lack of availability and expertise limit wider adoption.Hopefully, CMR will not have the same fate as Oedipous, who despite answering the Sphinx's riddle successfully, finally came to a bitter end; for in the case of CMR overcoming fate is, in fact, in our hands.
Harris, Julia G.; Bingham, Catherine A.; Morgan, Esi M.
Purpose of review To highlight efforts in pediatric rheumatology related to optimizing the care provided to patients with pediatric rheumatic diseases and describe various approaches to improve health outcomes. Recent findings Recent studies report low rates of remission, frequent occurrence of comorbidities, disease damage, and decreased health-related quality of life in pediatric rheumatic diseases. Pediatric Rheumatology Care and Outcomes Improvement Network is a quality improvement learning network that has demonstrated improvement in process of care measures through use of a centralized patient registry, and interventions including pre-visit planning, population management, shared decision making, and patient/parent engagement. A pediatric rheumatology patient-powered research network was established to enable patient and caregiver participation in setting research priorities and to facilitate data sharing to answer research questions. Quality measure development and benchmarking is proceeding in multiple pediatric rheumatic diseases. Summary This review summarizes the current efforts to improve care delivery and outcomes in pediatric rheumatic diseases through a learning health system approach that harnesses knowledge from the clinical encounter to serve quality improvement, research and discovery. Incorporating standard approaches to medication treatment plans may reduce variation in care. Including the patient voice to design of research studies brings focus on more patient relevant outcomes. (See Video, Supplemental Digital Content 1). PMID:26780426
Narváez, J A; Hernández-Gañán, J; Isern, J; Sánchez-Fernández, J J
Spinal involvement is common both in the spondyloarthritides and in rheumatoid arthritis, in which the cervical segment is selectively affected. Rheumatoid involvement of the cervical spine has characteristic radiologic manifestations, fundamentally different patterns of atlantoaxial instability. Magnetic resonance imaging (MRI) is the technique of choice for evaluating the possible repercussions of atlantoaxial instability on the spinal cord and/or nerve roots in patients with rheumatoid arthritis as well as for evaluating parameters indicative of active inflammation, such as bone edema and synovitis. Axial involvement is characteristic in the spondyloarthritides and has distinctive manifestations on plain-film X-rays, which reflect destructive and reparative phenomena. The use of MRI has changed the conception of spondyloarthritis because it is able to directly detect the inflammatory changes that form part of the disease, making it possible to establish the diagnosis early in the disease process, when plain-film X-ray findings are normal (non-radiographic axial spondyloarthritis), to assess the prognosis of the disease, and to contribute to treatment planning.
Lugo-Zamudio, Gustavo Esteban; Barbosa-Cobos, Rosa Elda; González-Ramírez, Laura Virginia; Delgado-Ochoa, Dolores
Deaths due to tuberculosis have reached 2.5 million cases per year worldwide. Poncet's disease is an infrequent form of tuberculosis characterised by a clinical picture of polyarthritis. A 24-year-old male presented with morning stiffness, arthralgias, bilateral symmetric arthritis of the proximal interphalangeal joints, wrists, knees, ankles, and shoulders, and adenomegalies at the cervical, submandibular, left supraclavicular, axillary and inguinal levels, without fever. Laboratory results were as follows: ESR 44mm/h, C-reactive protein 4.35, normal levels of complement C3 and C4, negative rheumatoid factor and anticyclic citrullinated peptide antibodies, positive antinuclear antibodies with fine speckled pattern (1:320) and cytoplasm (1:160) pattern and negative anti-Smith, -double-stranded DNA, Sjogren's syndrome-antigen A and Sjogren's syndrome-antigen B. Histological report of cervical node tissue revealed granulomatous lesions compatible with tuberculosis. Rheumatoid arthritis and systemic lupus erythematosus were ruled out. Anti-tuberculosis agents were initiated that resolved the clinical picture. Diagnosis of Poncet's disease was confirmed. The differential diagnosis between tuberculosis and autoimmune inflammatory joint diseases is a clinical challenge. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.
Feuchtenberger, Martin; Schäfer, Arne; Philipp Nigg, Axel; Rupert Kraus, Michael
Background: Only limited data are available on the prevalence of hepatitis B in patients with proven rheumatic diseases and thus the risk of reactivation under immunosuppressive therapy. Objective: To analyse hepatitis B serology in patients with rheumatic diseases prior to therapy. Method: In total, 1,338 patient records were analysed for HBsAg, HBsAb and HBcAb in a cross-sectional, single-centre study between 2011 and 2015 at first presentation. Data acquisition was realized using electronic patient files created during routine care. The main variables considered as predictors for HBV reactivation included (i) the exact type of rheumatic disease and (ii) the therapeutically induced immunosuppression. Results: Overall, 5.9% of patients (n=79) had proven contact with hepatitis B (HBcAb positive), and HBsAb were not detected in 1.3% (n=18). The rate of vaccinated subjects was 7.8%. HBsAg was detected in 3 patients (0.2%). In addition, 70.3% of patients were treated during the course of rheumatologic disease previously or currently with glucocorticoids, 85.2% with disease-modifying anti-rheumatic drugs (DMARDs) and 20.1% with a biologic agent (e.g., anti-IL-6, anti-TNFalpha, anti-CD20, CTLA4Ig or anti-IL-12/23). Conclusion: Prevalence of hepatitis B serostatus in the analysed rheumatic patients regarding HBs-Ag and HBcAb with or without HBsAb prior to therapy does not differ from the data published for the general population in Germany. However, the rate of hepatitis B vaccinated patients was lower. In general, a significant portion of patients (5.9%) has been exposed to HBV and therefore exhibited an increased risk of reactivation of hepatitis B when undergoing immunosuppressive therapy. PMID:27708728
García-Carrasco, M; Mendoza-Pinto, C; Macias Díaz, S; Vera-Recabarren, M; Vázquez de Lara, L; Méndez Martínez, S; Soto-Santillán, P; González-Ramírez, R; Ruiz-Arguelles, A
P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.
Dahan, Shani; Segal, Yahel; Shoenfeld, Yehuda
Today, we are facing a new era of digitization in the health care system, and with increased access to health care information has come a growing demand for safe, cost-effective and easy to administer therapies. Dietary habits have a crucial influence on human health, affecting an individual's risk for hypertension, heart disease and stroke, as well as influencing the risk of developing of cancer. Moreover, an individual's lifestyle choices can greatly influence the progression and manifestation of chronic autoimmune rheumatic diseases. In light of these effects, it makes sense that the search for additional therapies to attenuate such diseases would include investigations into lifestyle modifications. When considering the complex web of factors that influence autoimmunity, it is not surprising to find that several dietary elements are involved in disease progression or prevention. In this Review, several common nutritional components of the human diet are presented, and the evidence for their effects on rheumatic diseases is discussed.
Forseth, Karin Oien; Hafström, Ingiäld; Husby, Gunnar; Opava, Christina
To present the evidence for the efficacy of comprehensive rehabilitation in a warm climate of patients with a wide variety of rheumatic diseases. A systematic review of the literature was undertaken, searching in PubMed, Cinahl, Pedro, SweMed and Embase from 1970 to 2010, and using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation system) criteria. Six studies met the inclusion criteria. For patients with rheumatoid arthritis, moderate evidence was found for reduction of disease activity, pain, fatigue, and global disease impact. The evidence was also moderate that comprehensive rehabilitation in a warm climate did not improve fitness or reduce activity limitation beyond levels reached by rehabilitation in Scandinavia. Among patients with ankylosing spondylitis, low evidence was found for reduction of disease activity, pain, joint range of motion, activity limitation, and global disease impact. In groups with mixed rheumatic diagnoses, low evidence was found for reduction of pain, activity limitation, global disease impact and improved health-related quality of life. No studies on psoriatic arthritis, osteoarthritis, fibromyalgia or osteoporosis were found. Well-designed studies to validate and improve the low-to-moderate evidence found for the efficacy of comprehensive rehabilitation in a warm climate among patients with inflammatory rheumatic disease are greatly needed.
Rajamannan, Nalini M.; Antonini-Canterin, Francesco; Moura, Luis; Zamorano, José L.; Rosenhek, Raphael A.; Best, Patricia JM.; Lloyd, Margaret A.; Rocha-Gonçalves, F.; Chandra, Sarat; Alfieri, Ottavio; Lancellotti, Patrizio; Tornos, Pilar; Baliga, Ragavendra R; Wang, Andrew; Bashore, Thomas; Ramakrishnan, S; Spargias, Konstantinos; Shuvy, Mony; Beeri, Ronen; Lotan, Chaim; Suwaidi, Jassim Al; Bahl, Vinay; Pierard, Luc A.; Maurer, Gerald; Nicolosi, Gian Luigi; Rahimtoola, Shahbudin H.; Chopra, H. K.; Pandian, Natesa G.
Rheumatic Heart Disease (RHD) is well known to be an active inflammatory process which develops progressive calcification and leaflet thickening over time. The potential for statin therapy in slowing the progression of valvular heart disease is still controversial. Retrospective studies have shown that medical therapy is beneficial for patients with calcific aortic stenosis and recently for rheumatic valve disease. However, the prospective randomized clinical trials have been negative to date. This article discusses the epidemiologic risk factors, basic science, retrospective and prospective studies in valvular heart disease and a future clinical trial to target RHD with statin therapy to slow the progression of this disease. Recent epidemiological studies have revealed the risk factors associated with valvular disease include male gender, smoking, hypertension and elevated serum cholesterol and are similar to the risk factors for vascular atherosclerosis. An increasing number of models of experimental hypercholesterolemia demonstrate features of atherosclerosis in the aortic valve (AV), which are similar to the early stages of vascular atherosclerotic lesions. Calcification, the end stage process of the disease, must be understood as a prognostic indicator in the modification of this cellular process before it is too late. This is important in calcific aortic stenosis as well as in rheumatic valve disease. There are a growing number of studies that describe similar pathophysiologic molecular markers in the development of rheumatic valve disease as in calcific aortic stenosis. In summary, these findings suggest that medical therapies may have a potential role in patients in the early stages of this disease process to slow the progression of RHD affecting the valves. This review will summarize the potential for statin therapy for this patient population. PMID:19729684
Rajamannan, Nalini M; Antonini-Canterin, Francesco; Moura, Luis; Zamorano, Jose L; Rosenhek, Raphael A; Best, Patricia Jm; Lloyd, Margaret A; Rocha-Goncalves, F; Chandra, Sarat; Alfieri, Ottavio; Lancellotti, Patrizio; Tornos, Pilar; Baliga, Ragavendra R; Wang, Andrew; Bashore, Thomas; Ramakrishnan, S; Spargias, Konstantinos; Shuvy, Mony; Beeri, Ronen; Lotan, Chaim; Suwaidi, Jassim Al; Bahl, Vinay; Pierard, Luc A; Maurer, Gerald; Nicolosi, Gian Luigi; Rahimtoola, Shahbudin H; Chopra, K; Pandian, Natesa G
Rheumatic Heart Disease (RHD) is well known to be an active inflammatory process which develops progressive calcification and leaflet thickening over time. The potential for statin therapy in slowing the progression of valvular heart disease is still controversial. Retrospective studies have shown that medical therapy is beneficial for patients with calcific aortic stenosis and recently for rheumatic valve disease. However, the prospective randomized clinical trials have been negative to date. This article discusses the epidemiologic risk factors, basic science, retrospective and prospective studies in valvular heart disease and a future clinical trial to target RHD with statin therapy to slow the progression of this disease. Recent epidemiological studies have revealed the risk factors associated with valvular disease include male gender, smoking, hypertension and elevated serum cholesterol and are similar to the risk factors for vascular atherosclerosis. An increasing number of models of experimental hypercholesterolemia demonstrate features of atherosclerosis in the aortic valve (AV), which are similar to the early stages of vascular atherosclerotic lesions. Calcification, the end stage process of the disease, must be understood as a prognostic indicator in the modification of this cellular process before it is too late. This is important in calcific aortic stenosis as well as in rheumatic valve disease. There are a growing number of studies that describe similar pathophysiologic molecular markers in the development of rheumatic valve disease as in calcific aortic stenosis. In summary, these findings suggest that medical therapies may have a potential role in patients in the early stages of this disease process to slow the progression of RHD affecting the valves. This review will summarize the potential for statin therapy for this patient population.
Cellucci, Tania; Lee, Shirley; Webster, Fiona
Rare rheumatic diseases present unique challenges to knowledge translation (KT) researchers. There is often an urgent need to transfer knowledge from research findings into clinical practice to facilitate earlier diagnosis and better outcomes. However, existing KT frameworks have not addressed the specific considerations surrounding rare diseases for which gold standard evidence is not available. Several widely adopted models provide guidance for processes and problems associated with KT. However, they do not address issues surrounding creation or synthesis of knowledge for rare diseases. Additional problems relate to lack of awareness or experience in intended knowledge users, low motivation, and potential barriers to changing practice or policy. Strategies to address the challenges of KT for rare rheumatic diseases include considering different levels of evidence available, linking knowledge creation and transfer directly, incorporating patient and physician advocacy efforts to generate awareness of conditions, and selecting strategies to address barriers to practice or policy change.
Abdollahi-Roodsaz, Shahla; Abramson, Steven B; Scher, Jose U
The role of the gut microbiome in animal models of inflammatory and autoimmune disease is now well established. The human gut microbiome is currently being studied as a potential modulator of the immune response in rheumatic disorders. However, the vastness and complexity of this host-microorganism interaction is likely to go well beyond taxonomic, correlative observations. In fact, most advances in the field relate to the functional and metabolic capabilities of these microorganisms and their influence on mucosal immunity and systemic inflammation. An intricate relationship between the microbiome and the diet of the host is now fully recognized, with the microbiota having an important role in the degradation of polysaccharides into active metabolites. This Review summarizes the current knowledge on the metabolic role of the microbiota in health and rheumatic disease, including the advances in pharmacomicrobiomics and its potential use in diagnostics, therapeutics and personalized medicine.
Sidenco, Elena-Luminita; Ristache, Sanda; Belu, Luminita
We consulted 189 patients, with different locomotory diseases: degenerative, posttraumatic and chronic inflammatory rheumatic diseases. We followed the main clinical parameters: pain, limitation of mobility, affected function, inflammation and disorders of sensitivity. We applied an infrared LASER source of 100 mW (BTL), daily, for 5 days. The tolerance of the patients at the LASER treatment was excellent (100%). The evolution of the clinical parameters was variated, but inflammation, limitation of mobility and the affected function significantly improved (30-50%). We found a significant diminution of pain (27- 39%). We believe the LASER treatment in ambulatory conditions is essential for the function of the patients with different locomotory diseases.
Rheumatic fever (RF) and rheumatic heart disease (RHD) are significant causes of World Health Organization (WHO) and International Society and Federation of Cardiology (ISFC) initiated an International Programme for Prevention of RF/RHD in 16 developing countries, including Jamaica. The Jamaican RF/RHD National Control Programme began in July 1985. The Control Programme promotes the primary prevention of RF/RHD through the appropriate treatment of streptococcal throat infections. Secondary prevention has been the main focus of the Control Programme by administration of benzathine penicillin injections every four weeks to RF/RHD patients. Case finding activities have included two retrospective surveys of case records of RF/RHD patients admitted to the major hospitals in Kingston and St Andrew in the period 1975-1985 (Survey A) and 1989-1995 (Survey B). These surveys provided clinical and laboratory data on RF/RHD in Jamaican patients which were documented and analysed. Records of 1079 patients were reviewed in Survey A and records of 512 patients were reviewed in Survey B. Seventy-seven per cent of 524 patients were aged 5-15 years in initial attacks of RF in Survey A and in Survey B, 82% of 119 patients were between 5 and 15 years in initial attacks. There was no significant sex difference in RF in Survey A and Survey B. A diagnosis of RF had been made in 54% of records in Survey A and 55% of records in Survey B. Diagnosis conformed to the Modified Jones criteria. Carditis occurred in 41% and 70% of RF patients, respectively in survey A and B. Polyarthritis occurred in 73% in Survey A and 74% in Survey B. Chorea occurred in 3% of RF patients in both surveys. Erythema marginatum and subcutaneous nodules occurred rarely in both surveys. Evidence of recent streptococcal infections in RF was found in 74% and 64% in Survey A and B, respectively. Severe carditis occurred in 7% of initial attacks of RF in A and 26% in B. In RHD, mitral incompetence was the commonest
Rosenbaum, James T; Asquith, Mark J
The microbiome is the term that describes the microbial ecosystem that cohabits an organism such as humans. The microbiome has been implicated in a long list of immune-mediated diseases which include rheumatoid arthritis, ankylosing spondylitis, and even gout. The mechanisms to account for this effect are multiple. The clinical implications from observations on the microbiome and disease are broad. A growing number of microbiota constituents such as Prevotella copri, Porphyromonas gingivalis, and Collinsella have been correlated or causally related to rheumatic disease. The microbiome has a marked effect on the immune system. Our understanding of immune pathways modulated by the microbiota such as the induction of T helper 17 (Th17) cells and secretory immunoglobulin A (IgA) responses to segmented filamentous bacteria continues to expand. In addition to the gut microbiome, bacterial communities of other sites such as the mouth, lung, and skin have also been associated with the pathogenesis of rheumatic diseases. Strategies to alter the microbiome or to alter the immune activation from the microbiome might play a role in the future therapy for rheumatic diseases.
Singh, Swati; Kaushal, Ankur; Gupta, Sunil; Kumar, Ashok
An impedimetric mga gene specific DNA sensor was developed by immobilization of single stranded DNA probe onto the screen printed modified gold-dendrimer nanohybrid composite electrode for early and rapid detection of S. pyogenes in human throat swab samples causing rheumatic heart disease. Electrochemical impedance response was measured after hybridization with bacterial single stranded genomic DNA (ssG-DNA) with probe. The sensor was found highly specific to S. pyogenes and can detect as low as 0.01 ng ssDNA in 6 µL sample only in 30 min. The nanohybrid sensor was also tested with non-specific pathogens and characterized by FTIR. An early detection of the pathogen S. pyogenes in human can save damage of mitral and aortic heart valves (rheumatic heart disease) by proper medical care.
Koshi, Grace; Benjamin, V.; Cherian, George
A preliminary pilot study of streptococcal infection and sequelae was initiated in 23 villages in 1973 using trained field workers for case detection. Part of the pilot programme, in 1974-75, involved 374 rural and 664 urban schoolchildren, and revealed that 14.9% of them had streptococcal pyoderma while pharyngitis was seen in 4.2%. The pilot study also revealed a high prevalence of rheumatic fever (RF) and rheumatic heart disease (RHD) in both rural (5.4/1000) and urban (6.0/1000) pupils. A long-term surveillance study was then undertaken in 3890 pupils attending 15 rural schools, from July 1975 to December 1978, when the prevalence of RF was found to be 0.5/1000 and of RHD, 4.4/1000, giving an overall rate of 4.9/1000. The incidence rate was found to be 1.7/1000 per year in 1976, 1.6/1000 per year in 1977, and 0 in 1978. The rate of compliance with primary prophylaxis was 90-100%, and with secondary prophylaxis was 92-93% of the 27 cases. PMID:7032733
Catarino, Sandra Jeremias dos Santos; Boldt, Angelica Beate Winter; Beltrame, Marcia Holsbach; Nisihara, Renato Mitsunori; Schafranski, Marcelo Derbli; de Messias-Reason, Iara Jose
MASP-2 is a key protein of the lectin pathway of complement system. Several MASP2 polymorphisms were associated with MASP-2 serum levels or functional activity. Here we investigated a possible association between MASP2 polymorphisms and MASP-2 serum levels with the susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD). We haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 145 patients with history of RF from south Brazil (103 with RHD and 42 without cardiac lesion [RFo]) and 342 healthy controls. MASP-2 levels were determined by ELISA. The low MASP-2 producing p.377A and p.439H variants were negatively associated with RF (P=0.02, OR=0.36) and RHD (P=0.01, OR=0.25). In contrast, haplotypes that share the intron 9 - exon 12 g.1961795C, p.371D, p.377V and p.439R polymorphisms increased the susceptibility to RHD (P=0.02, OR=4.9). MASP-2 levels were associated with MASP2 haplotypes and were lower in patients (P<0.0001), which may reflect protein consumption due to complement activation. MASP2 gene polymorphisms and protein levels seem to play an important role in the development of RF and establishment of RHD.
Guilherme, Luiza; Ferreira, Frederico Moraes; Köhler, Karen Francine; Postol, Edilberto; Kalil, Jorge
Streptococcus pyogenes causes severe, invasive infections such as the sequelae associated with acute rheumatic fever, rheumatic heart disease, acute glomerulonephritis, uncomplicated pharyngitis, and pyoderma. Efforts to produce a vaccine against S. pyogenes began several decades ago, and different models have been proposed. We have developed a vaccine candidate peptide, StreptInCor, comprising 55 amino acid residues of the C-terminal portion of the M protein and encompassing both the T- and B-cell protective epitopes. The present article summarizes data from the previous 5 years during which we tested the immunogenicity and safety of StreptInCor in different animal models. We showed that StreptInCor overlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules. These results are consistent with peptides that have a universal vaccine epitope. The tridimensional molecular structure of StreptInCor was elucidated by nuclear magnetic resonance spectroscopy, which showed that its structure is composed of two microdomains linked by an 18-residue α-helix. Additionally, we comprehensively evaluated the structural stability of the StreptInCor peptide in different physicochemical conditions using circular dichroism. Additional experiments were performed with inbred, outbred, and HLA class II transgenic mice. Analysis of several organs of these mice showed neither deleterious nor autoimmune reactions even after a long period of vaccination, indicating that the StreptInCor candidate peptide could be considered as an immunogenic and safe vaccine.
Kim, Lucia; Kim, Do Kyun; Yang, Woo Ick; Shin, Dong Hwan; Jung, Ick Mo; Park, Han Ki; Chang, Byung Chul
For the purpose of determining the pathogenic role of transforming growth factor-beta1 (TGF-beta 1) in the mechanism of chronic rheumatic heart disease, we evaluated the expression of TGF-beta 1, proliferation of myofibroblasts, and changes in extracellular matrix components including collagen and proteoglycan in 30 rheumatic mitral valves and in 15 control valves. High TGF-beta 1 expression was identified in 21 cases (70%) of rheumatic mitral valves, whereas only 3 cases (20%) of the control group showed high TGF-beta 1 expression (p<0.001). Additionally, increased proliferation of myofibroblasts was observed in the rheumatic valves. High TGF-beta1 expression positively correlated with the proliferation of myofibroblasts (p=0.004), valvular fibrosis (p<0.001), inflammatory cell infiltration (p=0.004), neovascularization (p=0.007), and calcification (p<0.001) in the valvular leaflets. The ratio of proteoglycan to collagen deposition inversely correlated with TGF-beta 1 expression in mitral valves (p=0.040). In conclusion, an ongoing inflammatory process, the expression of TGF-beta 1, and proliferation of myofibroblasts within the valves have a potential role in the valvular fibrosis, calcification, and changes in the extracellular matrix that lead to the scarring sequelae of rheumatic heart disease.
Siakavellas, Spyros I; Sfikakis, Petros P; Bamias, Giorgos
TNF-like cytokine 1A (TL1A) and its receptors, death receptor 3 (DR3) and decoy receptor 3 (DcR3) are members of the TNF and TNF receptor superfamilies of proteins, respectively. They constitute a cytokine system that actively interferes with the regulation of immune responses and may participate in the pathogenesis of autoimmune diseases. This review aims to present the current knowledge on the role of the TL1A/DR3/DcR3 system in the pathophysiology of autoimmune rheumatic diseases, with a focus on rheumatoid arthritis (RA). An extensive literature search was performed in the PubMed database using the following keywords: TL1A, death receptor 3, DR3, decoy receptor 3, DcR3, TNFSF15, TNFRSF25, and TNFSF6B. Studies were assessed and selected in view of their relevance to autoimmune rheumatic diseases. The TL1A/DR3/DcR3 axis is a novel immune pathway that participates in the pathogenesis of a variety of autoimmune rheumatic diseases. These molecules may be promising therapeutic targets for inflammatory arthritis. Copyright © 2015 Elsevier Inc. All rights reserved.
Branch, D W
The obstetric management of the pregnant rheumatic patient is largely dictated by the specific disease and the degree to which it is associated with recognizable and treatable adverse obstetric outcomes, maternal or fetal. This review will cover the obstetric management of women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), rheumatoid arthritis (RA) and systemic sclerosis (SSc). Most experts agree that a co-ordinated management effort on the part of obstetricians and rheumatologists will likely yield the optimal achievable results.
Jacobs, J W; Rasker, J J; Van Riel, P L; Gribnau, F W; van de Putte, L B
To evaluate the effectiveness of several types of complementary medicine in patients with rheumatic diseases, a literature search was performed. Clinical trials, blind or open, comparing the effectiveness of forms of complementary medicine with that of placebo or another control therapy in patients with rheumatoid arthritis, osteoarthritis, soft tissue rheumatism and the fibromyalgia syndrome were selected until half of 1989, using electronic databases. Abstracts and summaries were excluded. The investigation was performed at the department of rheumatology of the Medisch Spectrum Twente hospital at Enschede in cooperation with the department of internal diseases of the Sint Radboud hospital at Nijmegen. For each type of complementary treatment, the results of all the clinical trials were summarized. Furthermore, the placebo-controlled trials were graded according to convincing trials or trials that seemed to be less valid and/or difficult to interpret. Data concerning acupuncture, balneotherapy, dietary measures, enzymic therapy, Seatone, homeopathy, manual therapy and fever few were found. Of these types of complementary medicine in rheumatic diseases, we found no convincing prove that they are more effective than the control or placebo treatment. A considerable number of the studies however can be criticized. It is necessary to perform further studies on the effect of frequently used types of complementary medicine in patients with rheumatic diseases, by or in cooperation with the physicians or paramedics who prescribe or perform these kinds of treatment. This is nearly always possible; directives are given to realize further studies of this kind. If a particular treatment proves to be no more effective than placebo treatment, its use should be discouraged.
Molokhia, Mariam; McKeigue, Paul
Risk of systemic lupus erythematosus (SLE) is high in west Africans compared with Europeans, and risk of rheumatoid arthritis (RA) is high in Native Americans compared with Europeans. These differences are not accounted for by differences in allele or haplotype frequencies in the human leucocyte antigen (HLA) region or any other loci known to influence risk of rheumatic disease. Where there has been admixture between two or more ethnic groups that differ in risk of disease, studies of the relationship of disease risk to proportionate admixture can help to distinguish between genetic and environmental explanations for ethnic differences in disease risk and to map the genes underlying these differences. PMID:11094421
Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfá, Eloisa; Srougi, Miguel; Clovis, A
ABSTRACT Background Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. Materials and Methods A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. Results A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Conclusions Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy. PMID:27120778
Szabó, Andrea; Zelkó, Romána; Antal, István
Present work provides an overall study about the types and the medicinal treatment of the rheumatic diseases especially the intraarticular formulations. Due to the localized nature of the joint, intraarticular injections are very favourable drug delivery systems. It has a big advantage over the oral medication; the systemic side effects are kept away. The review shows two types of the rheumatic diseases on the example of the healthy joint: the joint damage (osteoarthritis) and the inflamed joint (rheumatoid arthritis). There are many active ingredients for the treatment of the rheumatic diseases but the number of the intraarticular products is limited. At present are only formulations with hyaluronic acid or glucocorticoid on the market. Several physiological and biopharmaceutical aspects must be considered for the design of intraarticular injections. During and after the production many quality requirements have to be complied. On the market the formulations in solution or in suspension are available, which provide a short-term effect. The aim of the developments is to achieve long-term effect based on nano- or microparticles.
Bertrand, E; Gérard, R
This study reports the results of a multicentre enquiry performed in France in 1990 which included 41,242 adults hospitalised in Cardiology Units, 33,907 children hospitalised in Pediatric departments and 8,868 soldiers. A comparative enquiry was also carried out in North Africa (Tunis) and West Africa (Abidjan, Ouagadougou). The results of the French arm of the enquiry showed that rheumatic heart disease (RHD) has become very rare in adults (3.1% of all cardiac disease) and that it tends to occur in older subjects (average 54.4 years of age). There is practically no RHD in young adults. This decreased prevalence of RHD is confirmed in children in whom this diagnosis represents only 0.04% of cases of all cardiac disease--of which 87.5% are of extra-European origin. In contrast, there is a high frequency of RHD in Tunisia (29.3%) and West Africa (13.2% in Abidjan and 13% in Ouagadougou). The disease remains active as is shown by the age of affected adults in Africa (average 21 and 27 years of age). The results also show a reduction to a very low prevalence of acute rheumatic fever in French pediatric departments (0.005%). The authors discuss the reasons for the persistence of endemic infection in Africa: virulence of the streptococcus, predisposing factors (HLA group?), geographic factors and, above all, socioeconomic factors and difficulties in obtaining treatment and prophylaxis. A movement of international cooperation is suggested in order to combat RHD in Africa, especially with regards to its prevention in childhood.(ABSTRACT TRUNCATED AT 250 WORDS)
Fabien, Nicole; Olsson, Nils-Olivier; Goetz, Joëlle; Johanet, Catherine; Escande, Andrée; Bardin, Nathalie; Sanmarco, Marielle; Andre, Chantal; Chevailler, Alain; Humbel, René-Louis; Chretien, Pascale; Monier, Jean-claude; Fortenfant, Françoise; Oksman, Françoise; Taillefer, Marie-France; Sibilia, Jean
Our objective was to evaluate the prevalence of autoantibodies to cyclic citrullinated peptides (anti-CCP aAbs) in a cohort of patients with a variety of inflammatory or non-inflammatory rheumatic diseases other than rheumatoid arthritis (RA). Six hundred and nine serum samples were tested for anti-CCP aAbs and for rheumatoid factor (RF) using enzyme-linked immunosorbent assays and immunonephelometry. The prevalence of anti-CCP aAbs and RF reached 10% and 25%, respectively, using the positive cutoff value suggested by the manufacturers. Using a higher cutoff value (50 U/ml) for both aAbs, the prevalence was lower with 6% and 16%, respectively. The specificity of both markers for RA thus reached 94% and 84%, respectively. Anti-CCP aAbs were found to be elevated in inflammatory and also in non-inflammatory rheumatic diseases in the same proportion. Clinical data obtained for 36 positive patients showed that 17% developed RA within 5 years. In conclusion, anti-CCP aAbs are clearly more specific than RF for RA. Follow-up of anti-CCP aAbs-positive patients with inflammatory or non-inflammatory rheumatic diseases other than RA could be important considering the predictive value of these aAbs for the development of RA.
Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at the time of conception and anti-phospholipid antibodies are responsible for most complications. Disease flares, pre-eclampsia, and thrombosis are the main maternal complications, whereas fetal loss and intrauterine growth restriction are the main fetal complications. Antirheumatic drugs used during pregnancy and lactation to control disease activity are corticosteroids, hydroxychloroquine, sulphasalzine, and azathioprine. Vaginal delivery is possible in most circumstances, with cesarean section being reserved for complications. PMID:21371350
Milojevic, Diana S; Ilowite, Norman T
The goals of treatment of rheumatic diseases in children are to control the disease process while ensuring normal nutrition, growth, and development. The choice of antirheumatic drugs is similar in children and adults, but the doses, treatment schedules, and susceptibility to toxicity can differ considerably. In addition to differences between adult and pediatric diseases themselves, it is important for the rheumatologist who treats children to be cognizant of the impact of nutritional, developmental, and growth issues and differential susceptibility to toxicity of various treatments.
Piotto, Daniela Gerent Petry; Len, Cláudio Arnaldo; Hilário, Maria Odete Esteves; Terreri, Maria Teresa Ramos Ascensão
To assess nailfold capillaroscopy in children and adolescents with autoimmune rheumatic diseases (juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma and mixed connective tissue disease) and relate it to clinical and laboratory findings and disease activity. Cross-sectional study assessing 147 patients by use of nailfold capillaroscopy as follows: 60 with juvenile idiopathic arthritis; 30 with systemic lupus erythematosus; 30 with juvenile dermatomyositis; 20 with localized scleroderma; four with systemic sclerosis; and three with mixed connective tissue disease. Clinical and laboratory tests and nailfold capillaroscopy were performed in all patients. The nailfold capillaroscopy was performed with an optical microscope (at 10- and 16-time magnifications) by the same observer. Most patients (76.2%) had normal nailfold capillaroscopy. The major changes in nailfold capillaroscopy, characterizing the scleroderma pattern, were observed in patients with juvenile dermatomyositis, systemic scleroderma and mixed connective tissue disease. There was no association between nailfold capillaroscopy and disease activity in patients with juvenile idiopathic arthritis, systemic lupus erythematosus and localized scleroderma. Disease activity and capillaroscopy were associated in patients with juvenile dermatomyositis. Nailfold capillaroscopy is a useful method to diagnose autoimmune rheumatic diseases and monitor disease activity.
Scotece, Morena; Conde, Javier; Gómez, Rodolfo; López, Verónica; Pino, Jesús; González, Antonio; Lago, Francisca; Gómez-Reino, Juan J.; Gualillo, Oreste
Patients with rheumatic diseases have an increased risk of mortality by cardiovascular events. In fact, several rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis are associated with a higher prevalence of cardiovascular diseases (CVDs). Although traditional cardiovascular risk factors have been involved in the pathogenesis of cardiovascular diseases in rheumatic patients, these alterations do not completely explain the enhanced cardiovascular risk in this population. Obesity and its pathologic alteration of fat mass and dysfunction, due to an altered pattern of secretion of proinflammatory adipokines, could be one of the links between cardiovascular and rheumatic diseases. Indeed, the incidence of CVDs is augmented in obese individuals with rheumatic disorders. Thus, in this paper we explore in detail the relationships among adipokines, rheumatic diseases, and cardiovascular complications by giving to the reader a holistic vision and several suggestions for future perspectives and potential clinical implications. PMID:22910888
Rheumatology patients frequently note the occurrence of stressful or traumatic life events prior to the onset of their illness and/or a relationship between stress and disease flares. For our patients, identifying causal events could represent an effort to give meaning to a chronic and often disabling disease, while noting a link between stress and flares may proffer a sense of control. Whatever purpose the report of stress as an etiological or maintaining factor may serve, the science exploring a causal relationship between stress and autoimmune disease onset and course is expanding. Moreover, stress can also induce symptoms such as pain via nonimmunological mechanisms. PMID:20587002
Diefenbach, Karen A; Breuer, Christopher K
Inflammatory bowel disease is an important cause of gastrointestinal pathology in children and adolescents. The incidence of pediatric inflammatory bowel disease is increasing; therefore, it is important for the clinician to be aware of the presentation of this disease in the pediatric population. Laboratory tests, radiology studies, and endoscopic procedures are helpful in diagnosing inflammatory bowel disease and differentiating between Crohn’s disease and ulcerative colitis. Once diagnosed, the goal of medical management is to induce remission of disease while minimizing the side effects of the medication. Specific attention needs to be paid to achieving normal growth in this susceptible population. Surgical management is usually indicated for failure of medical management, complication, or malignancy. Algorithms for diagnostic evaluation and treatment of pediatric inflammatory bowel disease are presented. The specific psychosocial issues facing these patients are also discussed in this review as are the future goals of research in the complex problem of pediatric inflammatory bowel disease. PMID:16718840
Pelvic Inflammatory Disease (PID) - CDC Fact Sheet Untreated sexually transmitted diseases (STDs) can cause pelvic inflammatory disease (PID), a ... tubal blockage; •• Ectopic pregnancy (pregnancy outside the womb); •• Infertility (inability to get pregnant); •• Long-term pelvic/abdominal ...
He, Vincent Y.F.; Condon, John R.; Zhao, Yuejen; Roberts, Kathryn; de Dassel, Jessica L.; Currie, Bart J.; Fittock, Marea; Edwards, Keith N.; Carapetis, Jonathan R.
Background: We investigated adverse outcomes for people with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) and the effect of comorbidities and demographic factors on these outcomes. Methods: Using linked data (RHD register, hospital, and mortality data) for residents of the Northern Territory of Australia, we calculated ARF recurrence rates, rates of progression from ARF to RHD to severe RHD, RHD complication rates (heart failure, endocarditis, stroke, and atrial fibrillation), and mortality rates for 572 individuals diagnosed with ARF and 1248 with RHD in 1997 to 2013 (94.9% Indigenous). Results: ARF recurrence was highest (incidence, 3.7 per 100 person-years) in the first year after the initial ARF episode, but low-level risk persisted for >10 years. Progression to RHD was also highest (incidence, 35.9) in the first year, almost 10 times higher than ARF recurrence. The median age at RHD diagnosis in Indigenous people was young, especially among males (17 years). The development of complications was highest in the first year after RHD diagnosis: heart failure incidence rate per 100 person-years, 9.09; atrial fibrillation, 4.70; endocarditis, 1.00; and stroke, 0.58. Mortality was higher among Indigenous than non-Indigenous RHD patients (hazard ratio, 6.55; 95% confidence interval, 2.45–17.51), of which 28% was explained by comorbid renal failure and hazardous alcohol use. RHD complications and mortality rates were higher for urban than for remote residents. Conclusions: This study provides important new prognostic information for ARF/RHD. The residual Indigenous survival disparity in RHD patients, which persisted after accounting for comorbidities, suggests that other factors contribute to mortality, warranting further research. PMID:27407071
Prahalad, S; Colbert, R A
Many nonrheumatic diseases of childhood present with musculoskeletal abnormalities. A significant proportion of these disorders have a genetic basis, many involving defects in structural proteins of the connective tissue. Chief among these are collagen mutations resulting in spondyloepiphyseal dysplasias and Ehlers-Danlos syndrome, as well as fibrillin defects associated with Marfan's syndrome. A variety of other chromosomal anomalies are associated with musculoskeletal abnormalities, and may result from as yet unidentified connective tissue defects. In addition, metabolic diseases may result in findings of hyper- or hypomobility, or carpal tunnel syndrome. Helpful clinical clues to identify nonrheumatologic musculoskeletal disease, as well as recent advances in our understanding of the genetic basis of several of these disorders, are reviewed here.
Woldu, Bethel; Bloomfield, Gerald S
Rheumatic heart disease (RHD) is a chronic valvular disease resulting after severe or repetitive episodes of acute rheumatic fever (ARF), an autoimmune response to group A Streptococcus infection. RHD has been almost eliminated with improved social and health infrastructure in affluent countries while it remains a neglected disease with major cause of morbidity and mortality in many low- and middle-income countries, and resource-limited regions of high-income countries. Despite our evolving understanding of the pathogenesis of RHD, there have not been any significant advances to prevent or halt progression of disease in recent history. Long-term penicillin-based treatment and surgery remain the backbone of a RHD control program in the absence of an effective vaccine. The advent of echocardiographic screening algorithms has improved the accuracy of diagnosing RHD and has shed light on the enormous burden of disease. Encouragingly, this has led to a rekindled commitment from researchers in the most affected countries to advocate and take bold actions to end this disease of social inequality.
Menezes, Rikitha; Pantelyat, Alexander; Izbudak, Izlem; Birnbaum, Julius
Abstract Patients with rheumatic diseases can present with movement and other neurodegenerative disorders. It may be underappreciated that movement and other neurodegenerative disorders can encompass a wide variety of disease entities. Such disorders are strikingly heterogeneous and lead to a wider spectrum of clinical injury than seen in Parkinson's disease. Therefore, we sought to stringently phenotype movement and other neurodegenerative disorders presenting in a case series of rheumatic disease patients. We integrated our findings with a review of the literature to understand mechanisms which may account for such a ubiquitous pattern of clinical injury. Seven rheumatic disease patients (5 Sjögren's syndrome patients, 2 undifferentiated connective tissue disease patients) were referred and could be misdiagnosed as having Parkinson's disease. However, all of these patients were ultimately diagnosed as having other movement or neurodegenerative disorders. Findings inconsistent with and more expansive than Parkinson's disease included cerebellar degeneration, dystonia with an alien-limb phenomenon, and nonfluent aphasias. A notable finding was that individual patients could be affected by cooccurring movement and other neurodegenerative disorders, each of which could be exceptionally rare (ie, prevalence of ∼1:1000), and therefore with the collective probability that such disorders were merely coincidental and causally unrelated being as low as ∼1-per-billion. Whereas our review of the literature revealed that ubiquitous patterns of clinical injury were frequently associated with magnetic resonance imaging (MRI) findings suggestive of a widespread vasculopathy, our patients did not have such neuroimaging findings. Instead, our patients could have syndromes which phenotypically resembled paraneoplastic and other inflammatory disorders which are known to be associated with antineuronal antibodies. We similarly identified immune-mediated and inflammatory markers
Ideguchi, Haruko; Ohno, Shigeru; Takase, Kaoru; Tsukahara, Toshinori; Kaneko, Takeshi; Ishigatsubo, Yoshiaki
We describe a 37-year-old woman with recurrent polyarthritis, and recurrent erythema nodosum on the flexible side of her left forearm. On an X-ray of the chest, infiltration of the right upper lobe was observed. Transcription-reverse transcription concerted reaction in sputum samples revealed Mycobacterium tuberculosis (M. tuberculosis). Resolution of the polyarthritis with anti-tuberculosis (TB) drugs occurred in 3 days. We diagnosed her with Poncet's disease (PD). PD is considered to be a reactive arthritis, which is a different entity from tuberculous arthritis. Although PD is a rare disease, we should be aware of it as one of the differential diagnoses, even in patients without typical symptoms of TB.
Because the pathophysiologic relationship between laboratory and clinical abnormalities in many of the rheumatologic diseases is still not clearly understood, the use of the investigations dealt with in this article is based only upon statistics. The interpretation of these tests is therefore highly dependent on the result of the initial clinical assessment. Having accepted this limitation, however, the rheumatologist has available a number of powerful tools which may be used to diagnose, classify, or prognosticate. ImagesFigure 1 PMID:21253052
Dougherty, Scott; Khorsandi, Maziar; Herbst, Philip
Rheumatic heart disease (RHD) is a disease of poverty, is almost entirely preventable, and is the most common cardiovascular disease worldwide in those under 25 years. RHD is caused by acute rheumatic fever (ARF) which typically results in cumulative valvular lesions that may present clinically after a number of years of subclinical disease. Therapeutic interventions, therefore, typically focus on preventing subsequent ARF episodes (with penicillin prophylaxis). However, not all patients with ARF develop symptoms and not all symptomatic cases present to a physician or are correctly diagnosed. Therefore, if we hope to control ARF and RHD at the population level, we need a more reliable discriminator of subclinical disease. Recent studies have examined the utility of echocardiographic screening, which is far superior to auscultation at detecting RHD. However, there are many concerns surrounding this approach. Despite the introduction of the World Heart Federation diagnostic criteria in 2012, we still do not really know what constitutes the most subtle changes of RHD by echocardiography. This poses serious problems regarding whom to treat and what to do with the rest, both important decisions with widespread implications for already stretched health-care systems. In addition, issues ranging from improving the uptake of penicillin prophylaxis in ARF/RHD-positive patients, improving portable echocardiographic equipment, understanding the natural history of subclinical RHD and how it might respond to penicillin, and developing simplified diagnostic criteria that can be applied by nonexperts, all need to be effectively tackled before routine widespread screening for RHD can be endorsed. PMID:28163427
Dougherty, Scott; Khorsandi, Maziar; Herbst, Philip
Rheumatic heart disease (RHD) is a disease of poverty, is almost entirely preventable, and is the most common cardiovascular disease worldwide in those under 25 years. RHD is caused by acute rheumatic fever (ARF) which typically results in cumulative valvular lesions that may present clinically after a number of years of subclinical disease. Therapeutic interventions, therefore, typically focus on preventing subsequent ARF episodes (with penicillin prophylaxis). However, not all patients with ARF develop symptoms and not all symptomatic cases present to a physician or are correctly diagnosed. Therefore, if we hope to control ARF and RHD at the population level, we need a more reliable discriminator of subclinical disease. Recent studies have examined the utility of echocardiographic screening, which is far superior to auscultation at detecting RHD. However, there are many concerns surrounding this approach. Despite the introduction of the World Heart Federation diagnostic criteria in 2012, we still do not really know what constitutes the most subtle changes of RHD by echocardiography. This poses serious problems regarding whom to treat and what to do with the rest, both important decisions with widespread implications for already stretched health-care systems. In addition, issues ranging from improving the uptake of penicillin prophylaxis in ARF/RHD-positive patients, improving portable echocardiographic equipment, understanding the natural history of subclinical RHD and how it might respond to penicillin, and developing simplified diagnostic criteria that can be applied by nonexperts, all need to be effectively tackled before routine widespread screening for RHD can be endorsed.
Tagoe, Clement E; Zezon, Anna; Khattri, Saakshi
Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis.
Hügle, Thomas; van Laar, Jacob M
Immunoablative therapy and hematopoietic stem cell transplantation (HSCT) is an intensive treatment modality aimed at 'resetting' the dysregulated immune system of a patient with immunoablative therapy and allow outgrowth of a nonautogressive immune system from reinfused hematopoietic stem cells, either from the patient (autologous HSCT) or a healthy donor (allogeneic HSCT). HSCT has been shown to induce profound alterations of the immune system affecting B and T cells, monocytes, and natural killer and dendritic cells, resulting in elimination of autoantibody-producing plasma cells and in induction of regulatory T cells. Most of the available data have been collected through retrospective cohort analyses of autologous HSCT, case series, and translational studies in patients with refractory autoimmune diseases. Long-term and marked improvements of disease activity have been observed, notably in systemic sclerosis, systemic lupus erythematosus, and juvenile idiopathic arthritis, and treatment-related morbidity and mortality have improved due to better patient selection and modifications of transplant regimens. Treatment-related mortality has decreased to approximately 7%. Prospective, randomised, controlled clinical trials are ongoing or planned in systemic sclerosis, systemic lupus erythematosus, and several nonrheumatological conditions. PMID:18947373
Chandnani, Harsha K; Jain, Renu; Patamasucon, Pisespong
Human infection with group C Streptococcus is extremely rare and a select number of cases have been reported to cause acute pharyngitis, acute glomerulonephritis, skin and soft tissue infections, septic arthritis, osteomyelitis, pneumonitis, and bacteremia. In pediatrics, this bacteria is known to cause epidemic food-borne pharyngitis, pneumonia, endocarditis, and meningitis, and has reportedly been isolated in the blood, meninges, sinuses, fingernail, peritonsillar abscess, and thyroglossal duct cyst, among others. Our patient was a 7-year-old previously healthy female who presented with abnormal movements of her upper body and grimaces of her face that progressively worsened over time. Initial laboratory resulted revealed 3+ protein on urinalysis and elevated antistreptolysin-O and anti-DNAse antibody levels, and echocardiogram showed mild-to-moderate mitral regurgitation. We describe a rare case of group C Streptococcus resulting in rheumatic heart disease in a child, with a detailed review of the literature pertaining to the diagnosis and management of this infection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early recognition of rheumatic heart disease is crucial in the overall outcome of the condition and therefore knowledge of the symptoms associated with condition is also imperative. Group C Streptococcus is rarely associated with rheumatic heart disease and most children exhibiting acute onset of common symptoms, such as chorea, fever, carditis, and rash (erythema marginatum) will present to the emergency department first. Increased awareness and prompt recognition, as done with this child, will result in proper follow-up and adequate management of this condition in all patients. Copyright © 2015 Elsevier Inc. All rights reserved.
Carmona, Loreto; Abasolo, Lydia; Descalzo, Miguel A; Pérez-Zafrilla, Beatriz; Sellas, Agustí; de Abajo, Francisco; Gomez-Reino, Juan J
To describe the risk of cancer in patients exposed to tumor necrosis factor (TNF) antagonists. The following 2 clinical cohorts were studied: (1) BIOBADASER 2.0: a registry of patients suffering from rheumatic diseases exposed to TNF antagonists (2531 rheumatoid arthritis (RA), 1488 spondyloarthropathies, and 675 other rheumatic conditions); and (2) EMECAR: a cohort of 789 RA patients not exposed to TNF antagonists. Cancer incidence rates (IR) per 1000 patient-years and incidence rate ratios (IRR) were calculated for BIOBADASER 2.0 and EMECAR patients. The IR over time in BIOBADASER 2.0 patients was analyzed by joinpoint regression. The IRR was estimated to compare cancer rates in exposed versus nonexposed RA patients. Standardized incidence and mortality ratios (SIR, SMR) were also estimated. Risk factors for cancer in patients exposed to TNF antagonists were investigated by generalized linear models. The SMR for cancer in BIODASER 2.0 was 0.67 (95% CI: 0.51-0.86), and the SIR was 0.1 (95% CI 0.03-0.23). The IR in RA patients exposed to TNF antagonists was 5.8 (95% CI: 4.4-7.6), and the adjusted IRR was 0.48 (95% CI: 0.09-2.45). The IR in patients with previous cancer was 26.4 (95% CI: 4.1-171.5). Age, chronic obstructive pulmonary disease, and steroids were associated with a higher risk of developing cancer. The IR decreased after the first 4 months of exposure, without statistical significance. Overall cancer and mortality rates in patients with rheumatic diseases exposed to TNF antagonists are no higher than in the background Spanish population. However special attention should be paid to elderly patients, those with previous cancers, and patients treated with steroids. Copyright © 2011 Elsevier Inc. All rights reserved.
Beaton, Andrea; Richards, Hedda; Ploutz, Michelle; Gaur, Lasya; Aliku, Twalib; Lwabi, Peter; Ensing, Greg; Sable, Craig
Identification of patients with latent rheumatic heart disease by echocardiography presents a unique opportunity to prevent disease progression. Myocardial strain is a more sensitive indicator of cardiac performance than traditional measures of systolic function. The objective of this study was to test the hypothesis that abnormalities in myocardial strain may be present in children with latent rheumatic heart disease. Standard echocardiography images with electrocardiogram gating were obtained from Ugandan children found to have latent rheumatic heart disease as well as control subjects. Traditional echocardiography measures of systolic function were obtained, and offline global longitudinal strain analysis was performed. Comparison between groups was performed using strain as a continuous (Mann-Whitney U-test) and categorical (cut-off 5th percentile for age) variable. Our study included 14 subjects with definite rheumatic heart disease, 13 with borderline rheumatic heart disease, and 112 control subjects. None of the subjects had abnormal left ventricular size or ejection fraction. Global longitudinal strain was lower than the 5th percentile in 44% of the subjects with any rheumatic heart disease (p=0.002 versus controls) and 57% of the subjects with definite rheumatic heart disease (p=0.03). The mean absolute strain values were significantly lower when comparing subjects with any rheumatic heart disease with controls (20.4±3.95 versus 22.4±4.35, p=0.025) and subjects with definite rheumatic heart disease with controls (19.9±4.25 versus 22.4±4.35, p=0.033). Global longitudinal strain is decreased in subjects with rheumatic heart disease in the absence of abnormal systolic function. Larger studies with longer-term follow-up are required to determine whether there is a role for strain to help better understand the pathophysiology of latent rheumatic heart disease.
Hofheinz, K; Ganzleben, I; Schliep, S; Wacker, J; Schett, G; Manger, B
In December 2014 a patient presented to our clinic with the clinical symptoms of vasculitis. However, treatment with glucocorticoids did not lead to any improvement; therefore, the differential diagnostics were extended to other indications and ultimately led to the diagnosis of scurvy. This article describes the clinical picture of scurvy and its relationship to rheumatic diseases based on a clinical case and additional information from the literature. Differences and similarities with important rheumatological disease symptoms are presented. Scurvy is a rare hypovitaminosis disease which can be manifested in different forms. In addition to vasculitis the symptoms can also resemble arthritis and hemarthrosis is a typical finding. These symptoms can be accompanied by unspecific manifestations, such as muscle pain and due to impaired collagen synthesis characteristic features, such as corkscrew hair can be observed. The causal therapy of scurvy is substitution of ascorbic acid. Scurvy is a rare differential diagnosis in the context of rheumatic diseases. The indications for scurvy can be a lack of response to immunosuppressive and immunomodulatory drugs as well as individual symptoms, such as corkscrew hair.
François, R J; Eulderink, F; Bywaters, E G
OBJECTIVES--To redefine and comment on terms on a pathological basis, in order to avoid the confusion due to the use of terms with different meanings, to standardise usage among clinicians, radiologists and pathologists, and to facilitate literature searches. METHODS--Within the Committee of Pathology of the European League against Rheumatism, a study group was set up to analyse the medical literature and common practice concerning the nomenclature of rheumatic spinal diseases. The group tried to amalgamate the main trends in the field, to reconcile etymology, historical background, morphology, and common practice. RESULTS--The group warns against use of the terms 'acquired hyperostosis syndrome', '(von) Bechterew's disease', 'Kümmel's disease', 'pseudospondylolisthesis', 'rheumatoid spondylitis', 'spondylarthropathy' in the sense of spondarthritis, and 'spondylosis'. It recommends intercorporal or interapophyseal rather than intervertebral (osteo) chondrosis, zygapophyseal diverticulum rather than cyst, disc hernia rather than prolapse, spondyloarthritis rather than spondyloarthropathy, marginal rather than anterior spondylitis, and discarthrosis. It proposes 'zygarthrosis' to designate zygapophyseal osteoarthrosis. CONCLUSIONS--Knowledge of the pathological basis of diseases and an understanding of the original definitions given by those who coined new terms make it possible to avoid most of the confusion arising from improper use of spinal terms. PMID:7677436
Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...
... Weström, L., Joesoef, R., Reynolds, G., Hagdu, A., Thompson, S.E. (1992). Pelvic inflammatory disease and fertility. A ... Weström, L., Joesoef, R., Reynolds, G., Hagdu, A., Thompson, S.E. (1992). Pelvic inflammatory disease and fertility. A ...
Vinet, Évelyne; Bernatsky, Sasha
Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are the most prevalent autoimmune rheumatic diseases, predominantly occurring in women during childbearing years. Research has focused on assessing the risk of immediate complications during SLE and RA pregnancies, with studies documenting a higher risk of adverse obstetric outcomes, such as preterm births and infants small for gestational age. Until recently, little was known regarding the long-term health of children born to affected women. We present a review of the current evidence regarding the risk of adverse health outcomes in SLE and RA offspring, and potential mechanisms involved in their pathogenesis.
Jarvis, James N
One of the least-appreciated advances in pediatric rheumatology over the past 25 years has been the delineation of the many ways in which children with rheumatic disease differ from adults with the same illnesses. Furthermore, we are now learning that paradigms that are useful in evaluating adults with musculoskeletal complaints have limited utility in children. Nowhere is that more true than in the use of commonly used laboratory tests, particularly antinuclear antibody (ANA) and rheumatoid factor (RF) assays. This short review will provide the practitioner with the evidence base that supports a more limited use of ANA and RF testing in children.
Ruscitti, Piero; Cipriani, Paola; Carubbi, Francesco; Liakouli, Vasiliki; Di Benedetto, Paola; Berardicurti, Onorina; Alesse, Edoardo; Giacomelli, Roberto
Several inflammatory diseases have been associated with increased bone resorption and fracture rates and different studies supported the relation between inflammatory cytokines and osteoclast activity. The main factor required for osteoclast activation is the stimulation by receptor activator of nuclear factor kappa-B ligand (RANKL) expressed on osteoblasts. In this context, interleukin- (IL-) 1β, one of the most powerful proinflammatory cytokines, is a strong stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that stimulates the osteoclastogenesis. The resulting effects lead to an imbalance in bone metabolism favouring bone resorption and osteoporosis. In this paper, we review the available literature on the role of IL-1β in the pathogenesis of bone loss. Furthermore, we analysed the role of IL-1β in bone resorption during rheumatic diseases and, when available, we reported the efficacy of anti-IL-1β therapy in this field. PMID:25954061
Quintana, Rosana; Silvestre, Adriana M R; Goñi, Mario; García, Vanina; Mathern, Nora; Jorfen, Marisa; Miljevic, Julio; Dhair, Daniel; Laithe, Matias; Conti, Silvana; Midauar, Fadua; Martin, Maria Celeste; Barrios, Maria Cecilia; Nieto, Romina; Prigione, Cristina; Sanabria, Alvaro; Gervasoni, Viviana; Grabbe, Emilio; Gontero, Romina; Peláez-Ballestas, Ingris; Pons-Estel, Bernardo A
This study aimed to estimate the prevalence of musculoskeletal disorders and rheumatic diseases among the indigenous Qom (Toba) population in the city of Rosario, Santa Fe, Argentina. An analytical cross-sectional study using methodology of the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) was performed. Subjects ≥18 years of age were interviewed by advanced students of medicine and nursing, bilingual translator-facilitators, and coordinators. Individuals with musculoskeletal pain (positive cases) were evaluated sequentially for 7 days by internists and rheumatologists for diagnosis and treatment. The study included 1656 individuals (77 % of the census population). Of these, 1020 (61.5 %) were female, with mean age of 35.3 (SD 13.9) years, and 1028 (62.0 %) were bilingual. The public health care system covers 87.1 % of the population. Musculoskeletal pain in the previous 7 days and/or at some time during their life was present in 890 subjects (53.7 %). Of those with pain in the last 7 days, 302 (64.1 %) subjects had an Health Assessment Questionnaire Disability Index (HAQ-DI) score ≥0.8. The most frequent pain sites were lumbar spine (19.3 %), knees (13.0 %), and hands (12.0 %). The prevalence of rheumatic diseases was as follows: mechanical back pain (20.1 %), rheumatic regional pain syndrome (2.9 %), osteoarthritis (4.0 %) rheumatoid arthritis (2.4 %), inflammatory back pain (0.2 %), systemic sclerosis (0.1 %), Sjögren syndrome (0.1 %), fibromyalgia (0.1 %), mixed connective tissue disease (0.06 %), and systemic lupus erythematosus (0.06 %). The prevalence of musculoskeletal disorders was 53.7 % and rheumatic diseases 29.6 %. Rheumatoid arthritis prevalence was 2.4 % using COPCORD methodology, one of the highest reported at present.
Major advances have been made in the pathogenesis of rheumatoid arthritis, spondyloarthritis and connective tissue diseases, leading to new biotherapies. In rheumatoid arthritis, the discovery of anti-citrulline antibodies (ACPA, anti-citrullinatedpeptide antibodies), whose specificity is between 95% and 98% and may be present before symptom onset, allowed early diagnosis and provided new pathological insights. Studies of the role of cytokines, B cells and co-stimulation of T cells revealed novel therapeutic targets. TNF inhibitors are effective in spondyloarthritis. In lupusandSjigren'ssyndrome, genes stimulatedby IFNtypel are hyper-expressed, along with BAFF (or BLyS), a B lymphocyte-activating cytokine.
Soltész, Pál; Kerekes, György; Dér, Henriett; Szücs, Gabriella; Szántó, Sándor; Kiss, Emese; Bodolay, Edit; Zeher, Margit; Timár, Orsolya; Szodoray, Péter; Szegedi, Gyula; Szekanecz, Zoltán
Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as the role of systemic inflammation including cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. The characteristics of vasculopathies may significantly differ depending on the underlying disease. While classical accelerated atherosclerosis has been associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or spondyloarthropathies (SpA), obliterative vasculopathy may rather be characteristic for systemic sclerosis (SSc) or mixed connective tissue disease (MCTD). Antiphospholipid antibodies have been implicated in vasculopathies underlying SLE, antiphospholipid syndrome (APS), RA and MCTD. There is also heterogeneity with respect to inflammatory risk factors. Cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) and immune complexes are primarily involved in arthritides, such as RA, SpA, as well as in SLE. On the other hand, autoantibodies including anti-oxLDL anti-cardiolipin and anti-β2GPI are rather involved in SLE- and APS-associated vasculopathies. Regarding the non-invasive assessment of vascular function, endothelial dysfunction, overt atherosclerosis and vascular stiffness may be indicated by brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and aortic pulse-wave velocity (PWV), respectively. These abnormalities have been described in most inflammatory rheumatic diseases. While ccIMT and stiffness are relatively stable, FMD may be influenced by many confounding factors. In addition to traditional vasculoprotection, immunosuppressive agents including corticosteroids, traditional and biologic DMARDs may have significant vascular and metabolic
Lee, Sang Yeob; Chung, Won Tae; Jung, Woo Jin; Lee, Sung Won
This retrospective study of 432 patients was conducted between 2000 and 2009 to compare immunosuppressive therapy responses in uveitis accompanied or unaccompanied by rheumatic diseases. We divided patients into two groups: uveitis related or unrelated to rheumatic diseases. The clinical improvement after treatment was measured at the end of the observation period. Of the 432 patients with uveitis, 33 (7.6%) patients suffered from associated rheumatic diseases and 399 (92.4%) patients did not. The groups showed similar clinical features, but the mean age at onset of uveitis was lower in the rheumatic disease group (44.06 ± 2.13 years vs. 48.23 ± 0.81 years). The rheumatic diseases included spondyloarthropathy (31%), Behcet's disease (27%), rheumatoid arthritis (18%), systemic lupus erythematosus (15%), Sjogren's syndrome (6%), and mixed connective tissue disease (3%). Erythrocyte sedimentation rate and C-reactive protein level were increased in uveitis associated with rheumatic diseases, whereas ocular complications were not. The response to immunosuppressive therapy was significantly increased in cases of uveitis associated with rheumatic diseases (P < 0.05). Therefore, during early treatment, uveitis accompanied by rheumatic diseases showed better response to immunosuppressive therapy and less frequent complications.
There are two main ways in which physicians will be urged to improve the outcome for their patients suffering from rheumatic diseases in the coming era, these are, early diagnosis and timely effective therapy. Current reserch suggests that in rheumatoid arthritis joint damage occurs early, often within the first 2 years and even in the absence of associating severe symptoms, is a call for action for primary care physicians as well as rheumatologists. Similarly in SLE patients, sometimes the treatments are ineffective or too toxic with sepsis or opportunistic infections often limiting their use or resulting in the death of the patient. As primary care physicians are the clinicians most frequently visited by patients with initial symptoms of the disease, they first need to learn when to suspect it as well as its complications, and when to refer the patient appropriately. Rheumatologists need to determine when and how to prescribe the most appropriate treatment, as well as how to incorporate the new drugs which are emerging on the scene. At the same time, earlier initiation of combination therapy with the disease modifying anti-rheumatic therapy holds an area of continued exploration. This new information has modified our approach to patients' management. The age of "wait and see" is over.
Tristano, Antonio G
Sexuality is a complex aspect of the human being's life and is more than of only the sexual act. Normal sexual functioning consists of sexual activity with transition through the phases from arousal to relaxation with no problems, and with a feeling of pleasure, fulfillment and satisfaction. Rheumatic diseases may affect all aspects of life including sexual functioning. The reasons for disturbing sexual functioning are multifactorial and comprise disease-related factors as well as therapy. In rheumatoid arthritis and ankylosing spondylitis patients, pain and depression could be the principal factors contributing to sexual dysfunction. On the other hand, in women with Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis sexual dysfunction is apparently most associated to vaginal discomfort or pain during intercourse. Finally, sexual dysfunction in patients with fibromyalgia could be principally associated with depression, but the characteristic symptoms of fibromyalgia (generalized pain, stiffness, fatigue and poor sleep) may contribute to the occurrence of sexual dysfunction. The treatment of sexual dysfunction will depend on the specific patient's symptoms, however, there are some general recommendations including: exploring different positions, using analgesics drug, heat and muscle relaxants before sexual activity and exploring alternative methods of sexual expression. This is a systemic review about the impact of several rheumatic diseases on sexual functioning. There are no previous overviews about this topic so far.
Watkins, David A; Johnson, Catherine O; Colquhoun, Samantha M; Karthikeyan, Ganesan; Beaton, Andrea; Bukhman, Gene; Forouzanfar, Mohammed H; Longenecker, Christopher T; Mayosi, Bongani M; Mensah, George A; Nascimento, Bruno R; Ribeiro, Antonio L P; Sable, Craig A; Steer, Andrew C; Naghavi, Mohsen; Mokdad, Ali H; Murray, Christopher J L; Vos, Theo; Carapetis, Jonathan R; Roth, Gregory A
Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study. We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod-MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty. We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age-standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age-standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub-Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability-adjusted life-years due to rheumatic heart disease globally. We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period. The health-related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.).
Permin, H; Aldershvile, J; Nielsen, J O
Two hundred and thirty-nine patients with different rheumatic diseases were investigated for serological markers of hepatitis B virus (HBV) infection. An increased prevalence of anti-HBs was found in patients with systemic lupus erythematosus. The total prevalence of HBV markers in patients with polymyalgia rheumatica, temporal arteritis, juvenile and adult rheumatoid arthritis (RA) and systemic sclerosis was not significantly different from age-matched controls. Remarkably, 6 patients were HBsAg-positive of whom 3 had RA (4%). Two patients with RA were "healthy' HBsAg carriers. The third patient had circulating HBeAg as well and had shown progression from acute hepatitis to cirrhosis during the time of observation. Three of 18 patients with polyarteritis nodosa were HBsAg- and HBeAg-positive, and all 3 were young men. Clinical improvement was seen in one of these patients and was associated with seroconversion from HBeAg to anti-HBe. Our data do not support the theory that HBV is an aetiological factor in rheumatic diseases except in some cases of polyarteritis nodosa. PMID:6127059
Rothstein, J M; Delitto, A; Sinacore, D R; Rose, S J
Clinical and experimental data indicate that long-term corticosteroid use leads to atrophy of the type 2 muscle fibers. The purpose of this study was to characterize and quantify the nature of muscle function in rheumatic disease patients who have been on long-term corticosteroid therapy. Quadriceps function (i.e., peak torque and power) in 19 patients (11 with rheumatoid arthritis, five with systemic lupus erythematosis, and 3 other) and 11 age- and activity-matched normal controls was measured with an isokinetic dynamometer (Cybex II), during four constant velocity movements. Power was significantly lower for the patients at all speeds. At the higher speeds the patients' deficit in power production increased as indicated by a difference in the slopes of power-velocity regression lines. Measures of peak torque could not be consistently used to differentiate the groups. Patients with rheumatic diseases receiving corticosteroids have a decreased ability to generate muscle power. The method described allows for quantification of these deficits in a clinical setting.
Vázquez-Del Mercado, M; Martín-Márquez, B T; Petri, M H; Martínez-García, E A; Muñoz-Valle, J F
Pregnancy is a phenomenon that is not totally understood, based on the complex molecular interactions between the mother and the embrio. Once the fecundation is completed the fetus starts to fight for survival. The first challenge is the implantation process and the second one is the interaction with the maternal immune system. This review discusses how the fetus avoids the immune system rejection, and the mechanisms that the maternal immune system adapts in order to be fit for a successful pregnancy. Also, we focus in this paper on the effects of pregnancy in rheumatic diseases, because the myriad clinical outcomes of the disease itself and the obstetric complications dependent of the disease implicated, as for example in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropaties and antiphospholipid syndrome (APS).
Kim, Ki-Jo; Lee, Saseong
The complex interaction of molecules within a biological system constitutes a functional module. These modules are then acted upon by both internal and external factors, such as genetic and environmental stresses, which under certain conditions can manifest as complex disease phenotypes. Recent advances in high-throughput biological analyses, in combination with improved computational methods for data enrichment, functional annotation, and network visualization, have enabled a much deeper understanding of the mechanisms underlying important biological processes by identifying functional modules that are temporally and spatially perturbed in the context of disease development. Systems biology approaches such as these have produced compelling observations that would be impossible to replicate using classical methodologies, with greater insights expected as both the technology and methods improve in the coming years. Here, we examine the use of systems biology and network analysis in the study of a wide range of rheumatic diseases to better understand the underlying molecular and clinical features. PMID:25750554
Osman, Gehan M; Abdelrahman, Sirageldin M K; Ali, Sulafa K M
Rheumatic fever (RF) and rheumatic heart disease RHD remain as one of the major cardiovascular problems in Sudanese children. The cornerstones for control of RF and RHD are primary and secondary preventions as adopted by Sudan's programme. This study aimed to describe and raise the paediatric doctors' awareness about prevention of RF and RHD using lectures. It was a prospective, cross-sectional, hospital based study, conducted in Khartoum. The study populations were paediatric doctors including house officers, medical officers and registrars. Data were collected through self-administered questionnaire, which was constructed to assess the doctor's awareness about RF and RHD prevention before and after attending lectures. Eighty seven doctors participated in the study. The results showed that the overall doctors' awareness about prevention of rheumatic fever and rheumatic heart disease was at average level. It was raised by intervention through lectures to good level. It is recommended to introduce training programs for physicians in order to improve doctors' awareness about prevention of RF and RHD. Such activities need to be conducted at regular intervals.
Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup
Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future.
Thornton, Judith; Rangaraj, Satyapal
Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy and hypertrophic osteoarthropathy. Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its treatment. To review the effectiveness and safety of disease-modifying anti-rheumatic drugs for the management of arthritis related to cystic fibrosis in adults and children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which comprises references identified from comprehensive electronic database handsearches of relevant journal and abstract books of conference proceedings.Date of most recent search: 10 July 2012. Randomised controlled trials which compared the efficacy and safety of disease-modifying anti-rheumatic drugs (e.g. methotrexate, gold, sulfasalazine, penicillamine, leflunomide, hydroxychloroquine and newer agents such as biologic disease modifying agents and monoclonal antibodies) with each other, with no treatment or with placebo for cystic fibrosis-related arthropathy or hypertrophic osteoarthropathy. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that cystic fibrosis-related arthritis can be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. But when episodic symptoms progress to persistent disease, disease-modifying anti-rheumatic drugs may be needed to limit the course of the disease. It is disappointing that no randomised controlled trials to rigorously evaluate these drugs could be found. This systematic review has identified the need for a well-designed adequately powered randomised controlled trial to assess the efficacy and safety of disease-modifying anti-rheumatic drugs for the
van der Goes, Marlies C; Jacobs, Johannes W; Bijlsma, Johannes W
Glucocorticoids play a pivotal role in the management of many inflammatory rheumatic diseases. The therapeutic effects range from pain relief in arthritides, to disease-modifying effects in early rheumatoid arthritis, and to strong immunosuppressive actions in vasculitides and systemic lupus erythematosus. There are multiple indications that adverse effects are more frequent with the longer use of glucocorticoids and use of higher dosages, but high-quality data on the occurrence of adverse effects are scarce especially for dosages above 10 mg prednisone daily. The underlying rheumatic disease, disease activity, risk factors and individual responsiveness of the patient should guide treatment decisions. Monitoring for adverse effects should also be tailored to the patient. Continuously balancing the benefits and risks of glucocorticoid therapy is recommended. There is an ongoing quest for new drugs with glucocorticoid actions without the potential to cause harmful effects, such as selective glucocorticoid receptor agonists, but the application of a new compound in clinical practice will probably not occur within the next few years. In the meantime, basic research on glucocorticoid effects and detailed reports on therapeutic efficacy and occurrence of adverse effects will be valuable in weighing benefits and risks in clinical practice.
Mecoli, Christopher A; Saylor, Deanna; Gelber, Allan C; Christopher-Stine, Lisa
Pneumocystis jiroveci pneumonia (PJP) is an opportunistic infection with high mortality among patients with underlying rheumatologic conditions. Given the paucity of prospective data to guide treatment, clinical guidelines to initiate PJP prophylaxis are based on expert opinion and identify patients on ≥20 mg daily prednisone for ≥4 weeks duration for treatment. Herein we describe the PJP experience in rheumatic disease over a 20-year period at a single academic medical centre to investigate this 20 mg threshold and risk associated with lymphocyte counts, co-existing lung disease and immunosuppressive medications. We conducted a retrospective review of all admitted patients who received a PJP or PCP ICD-9 code (136.3) from January 1996 through October 2015. Twenty-one cases of confirmed PJP (by immunofluorescence or polymerase chain reaction) were reviewed, averaging to one case/year. The most common underlying rheumatologic conditions were inflammatory myopathy, lupus, and granulomatosis with polyangiitis. None of these 21 patients was receiving PJP prophylaxis upon admission. Eighteen (86%) were receiving ≥20 mg prednisone daily at the time of PJP diagnosis. Of the 3 treated with <20 mg prednisone, all received concomitant immunosuppressive medications, 2 with cyclophosphamide. Overall, there was a 43% (9/21) mortality rate. Immunosuppressant medication use, interstitial lung disease, or lymphocyte count did not impact mortality risk. PJP portends high mortality yet is a largely preventable complication of rheumatic disease treatment. Consideration to initiate prophylaxis should be made for patients exceeding the daily 20 mg prednisone threshold, and those receiving cyclophosphamide.
The preferred drugs for the initial treatment of juvenile rheumatoid arthritis (JRA) are salicylates or other non-steroidal anti-inflammatory drugs (NSAID) such as tolmetin or naproxen. If the disease activity does not respond adequately to the treatment, slow-acting anti-rheumatic drugs (SAARD) such as oral gold agents, low-dose D-penicillamine, or sulfasalazine should be given in addition to NSAID. If the systemic manifestations are severe, corticosteroid therapy may be commenced. Furthermore, if the joint destruction is progressive, immunosuppressants such as methotrexate would be selected as the third-line drugs of choice. The safety and efficacy of SAARD and immunosuppressants for the treatment of children with JRA, however, have not yet been confirmed, as the adverse effects such as bone marrow suppression, oncogenicity and mutagenicity are sometimes intense. Consequently, the strict indications for use and new therapeutic concepts for the management of JRA based on its pathogenesis are required.
Larrosa, Marta; Surís, Xavier; Pueyo, María J; Auleda, Jaume; de la Puente, María Luísa
Rheumatic diseases (RDs) are among the most common chronic health problems of the Catalan adult population. They cause important problems for individuals, their families and for the society overall, with high direct and indirect economic costs. The Department of Health of Catalonia promoted the creation of a Master Plan for the rheumatic diseases, as a tool for planning an integral approach to these problems. To present the work methodology that has been used in the development of the Master Plan and its final proposals. First an analysis of the burden caused by these problems in our community was performed and the objectives of the Plan were established. Later, strategic lines were defined and work groups organized to analyze proposals for improvement, which after consensus were accepted. The proposals of the Plan comprise actions in the scope of prevention, rationalization in the use of resources and the formation of professionals among others. Changes in the health care model for RDs were proposed in order to improve specialized and primary care coordination with clinics and musculoskeletal functional units. The Master Plan recommends actions to improve the attention of the population through operative planning and the services to different providers. The Master Plan will establish the health policy action lines directed against these disorders. Copyright © 2011 Elsevier España, S.L. All rights reserved.
Maier, Alexander; Kommer, Vera
We report on a young women with acute rheumatic fever. Acute rheumatic fever has become a rare disease in Germany, especially in adults. This carries the risk that it can be missed in the differential diagnostic considerations of acute rheumatic disorders and febrile status. If rheumatic fever is not diagnosed and treated correctly, there is a considerable risk for rheumatic valvular heart disease. In this article diagnosis, differential diagnosis and therapy of rheumatic fever are discussed extensively.
... presentations/100171.htm Inflammatory bowel disease - series—Normal anatomy To ... gastrointestinal tract starts at the mouth, which leads to the esophagus, stomach, small intestine, colon, and finally, the rectum and ...
... Human Papillomavirus (HPV) Pelvic Inflammatory Disease (PID) STDs & Infertility STDs & Pregnancy Syphilis Trichomoniasis Other STDs See Also ... the upper genital tract. PID can lead to infertility and permanent damage of a womanâ€™s reproductive organs. ...
Sukkar, Samir G; Rossi, Edoardo
The hypothesis that oxidative stress favours flogistic and immune processes inducing autoimmune rheumatic diseases (ARDs) and their complications is still under discussion. In this review we take into consideration both the aetiopathological role of the diet in such diseases and the possible efficacy of dietary supports as adjuvants for the usual specific therapies. Moreover, we shall examine the hypothetical pathophysiological role of oxidative stress on ARDs and their complications, the methods for its evaluation and the possibility of intervening on oxidative pathways by means of nutritional modulation. It is possible that in the future we will be able to control connective pathology by associating an immuno-modulating therapy ('re-educating') with natural products having an anti-oxidant activity to current immunosuppressive treatment (which has potentially toxic effects).
Frenkel, Joost; Kuis, Wietse
Identification of the genes involved in hereditary periodic fever syndromes has led to the recognition of a new pathophysiological category, the autoinflammatory disorders. The main non-hereditary autoinflammatory disease in childhood is systemic juvenile idiopathic arthritis (sJIA), others being the chronic infantile neurological cutaneous arthropathy (CINCA) syndrome and the periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. Familial Mediterranean fever (FMF) has been traced to mutations in the MEFV gene. Mutations in the MVK gene, encoding the enzyme mevalonate kinase, cause the hyper-IgD periodic fever syndrome (HIDS). The tumour necrosis factor(TNF)-receptor-associated periodic syndromes (TRAPS) have been linked to mutations in theTNFRSF1A gene, encoding a TNF-alpha receptor, and the CIAS1 gene is mutated in familial cold autoinflammatory syndrome. We discuss how this knowledge has influenced diagnosis and treatment of these rare genetic disorders and how it might change our approach to the more common rheumatic diseases.
Hu, Changfeng; Lu, Lu; Wan, Jie-Ping; Wen, Chengping
Hydroxychloroquine (HCQ) is known as one of the most fascinating synthetic antimalarial drugs during the last 50 years. It is currently among the most commonly employed medicines for the clinical treatment of rheumatic diseases, especially systemic lupus erythematosus and rheumatoid arthritis. In related mechanism studies, it has been found that HCQ possesses various immunomodulatory and anti-inflammatory activities. In addition, the effects of HCQ on anti-platelet, metabolic pathways, and antineoplasticity have also been disclosed in more recent studies. These significant findings on HCQ suggest the potential therapeutic applications of HCQ for treatment of many diseases, such as cancers, skin disease, antiphospholipid syndrome, etc. This review focuses on recent in vitro and clinical trials on its pharmacological mechanisms, therapeutic activities, and potential adverse effects.
Beaton, Andrea; Okello, Emmy; Aliku, Twalib; Lubega, Sulaiman; Lwabi, Peter; Mondo, Charles; McCarter, Robert; Sable, Craig
Screening with portable echocardiography has uncovered a large burden of latent rheumatic heart disease (RHD) among asymptomatic children in endemic regions, the significance of which remains unclear. This study aimed to determine the 2-year outcomes for children with latent RHD diagnosed by echocardiographic screening. Children identified with latent RHD enrolled in a biannual follow-up program. Risk factors for disease persistence and progression were examined. Of 62 children, 51 (82 %) with latent RHD had a median follow-up period of 25 months. Of these 51 children, 17 (33.3 %) reported an interval sore throat or symptoms consistent with acute rheumatic fever (ARF). Of 43 children initially classified as having borderline RHD, 21 (49 %) remained stable, 18 (42 %) improved (to no RHD) and 4 (10 %) worsened to definite RHD. Of the 8 children initially classified as having definite RHD, 6 (75 %) remained stable, and 2 (25 %) improved to borderline RHD. Two children had confirmed episodes of recurrent ARF, one of which represented the sole case of clinical worsening. The risk factors for disease persistence or progression included younger age (p = 0.05), higher antistreptolysin O titers at diagnosis (p = 0.05), and more morphologic valve abnormalities (p = 0.01). After 2 years, most of the children had a benign course, with 91 % remaining stable or showing improvement. Education may improve recognition of streptococcal sore throat. Longer-term follow-up evaluation, however, is warranted to confirm disease progression and risk factor profile. This could help tailor screening protocols for those at highest risk.
Rousseau-Nepton, Isabelle; Lang, Bianca; Rodd, Celia
Glucocorticoids (GC) are a standard treatment for pediatric rheumatic disease. Recent literature highlights skeletal vulnerability in children with rheumatic illness, including vertebral and peripheral fractures and reductions in bone mineral density in longitudinal follow-up. Annual vertebral fracture incidence of 4-6 % in those recently diagnosed and prevalence of 7-28 % in those several years post diagnosis have been reported. The fractures are often asymptomatic, often thoracic in location, and usually of mild, anterior wedge morphology. Diseases with more systemic involvement and severe inflammation (SLE, JDM) seem to be at higher risk. Neither BMD nor GC dose are ideal predictors for risk of fractures. These children also seem to have an increased incidence of long-bone fractures, particularly in the forearm and wrist; in the scant literature, long-bone fractures are not predictive of vertebral fractures. Bone mass accrual is typically suboptimum across time, although the use of potent steroid-sparing anti-inflammatory agents may counteract the effects of GC and active disease. Vitamin D insufficiency warrants ongoing monitoring. Additional targeted studies are justified to increase understanding of bone health risks in this population.
After a short review on the manifold relations between rheumatic and pulmonary diseases this aspect is exemplified in detail by acute sarcoidosis. Report on 31 patients with Loefgren-Syndrome, admitted to the rheumatologic-cardiological clinic between 1968 to 1973, nearly all with the suspicion of rheumatic fever. Their symptoms, clinical findings as well as the diagnostic programme carried out is described.
Kuryliszyn-Moskal, Anna; Kaniewska, Katarzyna; Dzięcioł-Anikiej, Zofia; Klimiuk, Piotr Adrian
Rheumatic diseases such as osteoarthritis and rheumatoid arthritis constitute the most frequent pathological states leading to the development of foot deformities, which reduce quality of life and cause disability. The aim of the present study was to compare the results of plantoconturographic examinations, obtained by means of a computer podoscope, in osteoarthritis and rheumatoid arthritis patients. Special attention was paid to the differences in the values of each parameter determining the level of foot function. The study was performed in 94 female patients divided into two groups according to the type of disease. There were 54 patients with rheumatoid arthritis and 40 with osteoarthritis. The control group consisted of 34 healthy women. The plantographic assessment of static foot structure was carried out by means of a device for computer-aided foot examination. A fallen transverse arch of the right foot was statistically much more frequent in the rheumatoid arthritis patients than in osteoarthritis patients or the control group (p < 0.005 and p < 0.05, respectively). Significant differences in the values of the Wejsflog index were observed in the case of left foot between rheumatoid arthritis patients and the control group (p < 0.05). Similarly, there were statistically significant differences in the values of the hallux valgus angle (α) for the right foot between rheumatoid arthritis and osteoarthritis patients or control group (in both cases p < 0.05). Rheumatic diseases predispose patients to disturbances of static foot function. The obtained results highlight the importance of diagnosing foot static disturbances in the prevention of destructive changes affecting the functioning of osteoarthritis and rheumatoid arthritis patients.
Rojas, Carmen Maria Lara; Borella, Elisabetta; Palma, Lavinia; Ragozzino, Silvio; De Ramón, Enrique; Gomez-Huelgas, Ricardo; Punzi, Leonardo; Doria, Andrea
Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by buds of granulation tissue within lung distal airspaces. The diagnosis requires the histopathologic evidence of organizing pneumonia along with a suggestive clinical and radiographic pattern. This disorder is characterized by a good response to corticosteroids and an excellent prognosis. It can occur in association with a broad spectrum of clinical conditions or can be isolated, in this last case named cryptogenic organizing pneumonia. We searched for BOOP in patients with autoimmune rheumatic diseases (ARD) in the literature, and we found 32 well-documented cases. We reported here demographic features, manifestations, treatment and outcome of patients with BOOP associated with ARD. Notably, BOOP can be the presenting feature in some patients with ARD; thus, a close follow-up of patients with BOOP is recommended.
Liu, Bin; Shu, ShangAn; Kenny, Thomas P; Chang, Christopher; Leung, Patrick S C
The clinical management of autoimmune rheumatic diseases (ARD) has undergone significant changes in the last few decades, leading to remarkable improvements in clinical outcomes of many patients with mild to moderate ARD. On the other hand, severe refractory ARD patients often have high morbidity and mortality. Extensive basic research and clinical evidence has opened the door to new encouraging perspectives, such as the establishment of a role of stem cell transplantation (SCT) in the strategic management of ARD. Given the great heterogeneity of ARD, it is difficult to assign an optimal SCT regimen to all ARD patients. SCT remains a challenging mode of therapy in ARD patients from the standpoints of both efficacy and safety. As the clinical data of SCT in ARD increases and as we improve our understanding of stem cell biology and the downstream effects on the immune system, the future is promising for the development of optimal personalized SCT regimens in ARD.
Sidiropoulos, Prodromos I; Karvounaris, Stylianos A; Boumpas, Dimitrios T
Subjects with metabolic syndrome--a constellation of cardiovascular risk factors of which central obesity and insulin resistance are the most characteristic--are at increased risk for developing diabetes mellitus and cardiovascular disease. In these subjects, abdominal adipose tissue is a source of inflammatory cytokines such as tumor necrosis factor-alpha, known to promote insulin resistance. The presence of inflammatory cytokines together with the well-documented increased risk for cardiovascular diseases in patients with inflammatory arthritides and systemic lupus erythematosus has prompted studies to examine the prevalence of the metabolic syndrome in an effort to identify subjects at risk in addition to that conferred by traditional cardiovascular risk factors. These studies have documented a high prevalence of metabolic syndrome which correlates with disease activity and markers of atherosclerosis. The correlation of inflammatory disease activity with metabolic syndrome provides additional evidence for a link between inflammation and metabolic disturbances/vascular morbidity.
Batzloff, Michael R; Pandey, Manisha; Olive, Colleen; Good, Michael F
Rheumatic fever (RF) and rheumatic heart disease (RHD) are postinfectious complications of an infection (or repeated infection) with the Gram-positive bacterium, Streptococcus pyogenes (also known as group A streptococcus, GAS). RF and RHD are global problems and affect many indigenous populations of developed countries and many developing countries. However, RF and RHD are only part of a larger spectrum of diseases caused by this organism. The development of a vaccine against GAS has primarily targeted the abundant cell-surface protein called the M-protein. This review focuses on different M-protein-based-subunit vaccine approaches and the different delivery technologies used to administer these vaccine candidates in preclinical studies.
Firuzi, Omidreza; Fuksa, Leos; Spadaro, Chiara; Bousová, Iva; Riccieri, Valeria; Spadaro, Antonio; Petrucci, Rita; Marrosu, Giancarlo; Saso, Luciano
The involvement of oxidative stress in the pathogenesis of rheumatic disorders, such as systemic sclerosis (SSc) and chronic polyarthritides, has been suggested yet not thoroughly verified experimentally. We analysed 4 plasmatic parameters of oxidative stress in patients with SSc (n = 17), psoriatic arthritis (PsA) (n = 10) and rheumatoid arthritis (RA) (n = 9) compared with healthy subjects (n = 22). The biomarkers were: total antioxidant capacity (TAC) measured by ferric reducing antioxidant power (FRAP) method, hydroperoxides determined by ferrous ion oxidation in presence of xylenol orange (FOX) method and sulfhydryl and carbonyl groups assessed by spectrophotometric assays. The results showed significantly increased hydroperoxides in SSc, PsA and RA (3.97 +/- 2.25, 4.87 +/- 2.18 and 5.13 +/- 2.36 micromol L(-1), respectively) compared with the control group (2.31 +/- 1.40 micromol L(-1); P < 0.05). Sulfhydryls were significantly lower in SSc (0.466 +/- 0.081 mmol L(-1)), PsA (0.477 +/- 0.059 mmol L(-1)) and RA (0.439 +/- 0.065 mmol L(-1)) compared with the control group (0.547 +/- 0.066 mmol L(-1); P < 0.05). TAC in all three diseases showed no difference in comparison with controls. Carbonyls were significantly higher in RA than in the control group (32.1 +/- 42 vs 2.21 +/- 1.0 nmol (mg protein)(-1); P < 0.05). The obtained data indicate augmented free radical-mediated injury in these rheumatic diseases and suggest a role for the use of antioxidants in prevention and treatment of these pathologies.
Kremer, Joel M
The Corrona US national registry collects data concerning patient status from both the rheumatologist and patient at routine clinical encounters. Corrona has functioning disease registries in rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies, psoriasis and inflammatory bowel disease. Corrona merges data concerning long-term effectiveness and safety, as well as comparative and cost effectiveness of agents to treat these autoimmune diseases.
The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases. PMID:22975004
Kotulska, Anna; Kopeć-Mędrek, Magdalena; Grosicka, Anida; Kubicka, Monika
Objectives Erythrocyte sedimentation rate (ESR) and serum level of C-reactive protein (CRP) are the acute phase reactants most commonly determined in patients with rheumatic diseases. The indices are affected by different factors, but both of them are applied for evaluation of the disease activity in patients with inflammatory disorders of the musculoskeletal system. Material and methods The authors compared the results of ESR and CRP, which were carried out during routine diagnosis in 200 patients admitted to the Department of Rheumatology. Results A significant correlation between ESR and CRP was found (ESR after 1 h/CRP: correlation coefficient 0.6944, ESR after 2 h/CRP: correlation coefficient 0.6126). There was no difference in ESR or CRP between male and female patients, and patients older than 40 years had higher ESR and CRP. Conclusions The obtained results support the usefulness of both indices in the clinical practice of rheumatologists. PMID:27407254
Niklas, Karolina; Niklas, Arkadiusz A; Majewski, Dominik; Puszczewicz, Mariusz J
The majority of rheumatic diseases belong to the group of autoimmune diseases and are associated with autoantibody production. Their etiology is not fully understood. Certain medications and environmental factors may have an influence on the occurrence of rheumatic diseases. Establishing a cause-effect relationship between a certain factor and disease induction is not always simple. It is important to administer the drug continuously or monitor exposure to a given factor in the period preceding the onset of symptoms. The lack of early diagnosed autoimmune disease, or finally the lack of symptoms within a few weeks/months after discontinuation of the drug/cessation of exposure, is also important. The most frequently mentioned rheumatic diseases caused by drugs and environmental factors include systemic lupus erythematosus (SLE), scleroderma, systemic vasculitis, polymyositis, dermatomyositis, and Sjögren's syndrome. The objective of this study is to summarize current knowledge on rheumatic diseases induced by drugs and environmental factors.
Niklas, Karolina; Niklas, Arkadiusz A; Majewski, Dominik; Puszczewicz, Mariusz
The majority of rheumatic diseases belong to the group of autoimmune diseases and are associated with autoantibody production. Their etiology is not fully understood. Certain medications and environmental factors may have an influence on the occurrence of rheumatic diseases. Establishing a cause-effect relationship between a certain factor and disease induction is not always simple. It is important to administer the drug continuously or monitor exposure to a given factor in the period preceding the onset of symptoms. The lack of previously diagnosed autoimmune disease, or finally the lack of symptoms within a few weeks/months after discontinuation of the drug/cessation of exposure, is also important. The most frequently mentioned rheumatic diseases caused by drugs and environmental factors include systemic lupus erythematosus, scleroderma, systemic vasculitis, polymyositis, dermatomyositis, and Sjögren's syndrome. The objective of this study is to summarize current knowledge on rheumatic diseases induced by drugs and environmental factors.
Cutolo, Maurizio; Paolino, Sabrina; Pizzorni, Carmen
Several chronic inflammatory conditions and autoimmune diseases involving different organs and tissues have been found at risk of progression to cancer. A wide array of proinflammatory cytokines, prostaglandins, nitric oxide products, and matricellular proteins are closely involved in premalignant and malignant transition of cells almost always in a background of chronic inflammation. Interestingly, epigenetic perturbations (i.e. miRNA aberrations, altered DNA methylation) together with important steroid hormone metabolic changes (i.e. oestrogens), or the altered vitamin D concentrations that may unbalance the immune / inflammatory response, have been found linked to the risk and severity in several chronic inflammatory conditions, as well as in cancer. In particular, it is evident, that not only the parent oestrogen but also oestrogen metabolites should be taken into account when this process is evaluated, specially the formation of catecholoestrogen metabolites, that are capable of forming either stable or depurinating DNA adducts, which can cause extensive DNA damage. It is interesting that today the successful treatment of several chronic immune/inflammatory rheumatic diseases is obtained also by using medications initially developed for their use in oncology. The circadian increase of growth factors, specially during the late night, in both chronic inflammation and in cancer patients, as well as the presence of oestrogen-regulated circadian mechanisms, suggests further important links.
Al-Abd, Ahmed M; Inglis, Julia J; Nofal, Salwa M; Khalifa, Amani E; Williams, Richard O; El-Eraky, Wafaa I; Abdel-Naim, Ashraf B
Methotrexate is a disease modifying anti-rheumatic drug that is widely used for the treatment of rheumatoid arthritis. Nimesulide is a non-steroidal anti-inflammatory drug which is frequently used as adjuvant therapy for symptomatic alleviation of rheumatoid arthritis. In this study, we have evaluated the potential influence of nimesulide on the disease modifying anti-rheumatic properties of methotrexate using the collagen-induced arthritis model. Mice were immunized with collagen type II for the induction of arthritis and treated with methotrexate (2.5mg/kg) twice a week, nimesulide (20mg/kg) every other day or a combination of both drugs. Treatment started one week after the onset of arthritis until day 40. An arthritic index was used to compare the severity of arthritis between different treatments. In addition, articular hyperalgesia, joint stiffness, radiological deterioration and intra-articular leucocytic infiltration were evaluated. Methotrexate alone showed modest but significant analgesic and anti-inflammatory effects, and the effects of nimesulide were comparable. On the other hand, nimesulide significantly improved the disease modifying anti-rheumatic profile of methotrexate in terms of arthritic index and joint mobility. Furthermore, although nimesulide failed to show any radiological evidence of articular protection, it significantly improved methotrexate-induced joint protection as judged by X-ray analysis.
Morbach, H; Girschick, H J
The introduction of cytokine-targeted therapies has significantly improved the treatment options of rheumatic diseases; however, some patients are also refractory to these treatment measures. The B cells play a central role in the pathogenesis of many rheumatic diseases and B-cell targeted therapies are a promising option as second-line medication for treating patients with a refractory disease course. Randomized controlled trials analyzing the efficacy of B-cell directed therapies for childhood rheumatic diseases have not yet been performed. The use of the B-cell depleting antibody rituximab showed positive results in non-controlled case series of juvenile systemic lupus erythematosus (SLE) patients. Patients with a refractory disease course of oligoarticular or polyarticular juvenile idiopathic arthritis might also benefit from B-cell depletion using rituximab. The B cell-targeting therapies for the treatment of childhood rheumatic diseases should be initiated and closely supervised by a pediatric rheumatologist.
de Man, Yaël A; Dolhain, Radboud J E M; Steegers, Eric A P; Hazes, Johanna M W
Treatment of rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus and Bechterew's disease is still improving and the number of fertile patients with a wish to conceive will probably increase. New knowledge regarding the course of rheumatic diseases during pregnancy and post partum herald a change in the support of women with rheumatic diseases who desire to have children. Justified use of antirheumatic drugs before, during and after pregnancy is a key issue for a successful pregnancy. The newer agents such as tumour necrosis factor (TNF) alpha blocking agents can also be of use. Specific preconception care should be offered to women with rheumatic diseases to optimize and increase chances of a successful pregnancy.
Gaddy, Jasmine R.; Vista, Evan S.; Robertson, Julie M.; Dedeke, Amy B.; Roberts, Virginia C.; Klein, Wendy S.; Levin, Jeremy H.; Mota, Fabio H.; Cooper, Tina M.; Grim, Gloria A.; Khan, Sohail; James, Judith A.
Objectives Rheumatic diseases cause significant morbidity within American Indian populations. Clinical disease presentations, as well as historically associated autoantibodies, are not always useful in making a rapid diagnosis or assessing prognosis. The purpose of this study is to identify autoantibody associations among Oklahoma tribal populations with rheumatic disease. Methods Oklahoma tribal members (110 rheumatic disease patients and 110 controls) were enrolled at tribal-based clinics. Rheumatic disease patients (suspected or confirmed diagnosis) were assessed by a rheumatologist for clinical features, disease criteria, and activity measures. Blood samples were collected and tested for common rheumatic disease autoantibodies (ANA, anti-CCP, anti-RF, anti-Ro, anti-La, anti-Sm, anti-nRNP, anti-Ribosomal P, anti-dsDNA, and anti-cardiolipins). Results In patients with suspected systemic rheumatic diseases, 72% satisfied ACR classification: 40 (36%) rheumatoid arthritis, 16 (15%) systemic lupus erythematosus, 8 (7%) scleroderma, 8 (7%) osteoarthritis, 4 (4%) fibromyalgia, 2 (2%) seronegative spondyloarthropathy, 1 Sjogrens syndrome, and 1 sarcoidosis. When compared to controls, RA patient sera were more likely to contain anti-CCP (55% vs 2%, p<0.001) or anti-RF IgM antibodies (57% vs 10%, p<0.001); however, the difference was greater for anti-CCP. Anti-CCP positivity conferred higher disease activity scores (DAS28 5.6 vs 4.45, p=0.021) while anti-RF positivity did not (DAS28 5.36 vs 4.64, p=0.15). Anticardiolipin antibodies (25% or rheumatic disease paitents vs 10% of contros,; p=0.0022) and ANA (63% vs 21%, p<0.0001) were more common in rheumatic disease patients. Conclusion Anti-CCP may serve as a better RA biomarker in AI patients, while the clinical significance of increased frequency of aCLs needs further evaluation. PMID:22896022
Amor, B; Cherot, A; Delbarre, F
A study was made of 45 patients suffering from hydroxyapatite rheumatism (multiple tendon calcifications disease). There were 36 women and 9 men aged between 15 and 61 years with an average age of 14. The following joints were involved (the first figure refers to clinical affection, that between brackets to radiologically demonstrable calcifications): shoulder 34 (36); neck 14 (15); wrist 18 (11); fingers 19 (17); hip 11 (29); knee 14 (18); ankle 10 (14); foot 5 (6); spinal column 16 (24). In 30 patients the disease manifested itself in the form of acute recurrent migratory arthritis resembling gout. In 8 cases, it developed in the form of acute recurrent migratory arthritis resembling gout. In 8 cases, it developed in the form of acute polyarthritis and in 7 as rheumatoid arthritis without radiological lesions. Thirty-two patients could be followed up. Four of them were cured, 9 showed improvement but still suffered attacks of pain. Eighteen patients were not improved, their pains growing more chronic. Four patients had a family history of multiple tendon calcifications disease.
Menni, Cristina; Zierer, Jonas; Valdes, Ana M; Spector, Tim D
Metabolomics is an exciting field in systems biology that provides a direct readout of the biochemical activities taking place within an individual at a particular point in time. Metabolite levels are influenced by many factors, including disease status, environment, medications, diet and, importantly, genetics. Thanks to their dynamic nature, metabolites are useful for diagnosis and prognosis, as well as for predicting and monitoring the efficacy of treatments. At the same time, the strong links between an individual's metabolic and genetic profiles enable the investigation of pathways that underlie changes in metabolite levels. Thus, for the field of metabolomics to yield its full potential, researchers need to take into account the genetic factors underlying the production of metabolites, and the potential role of these metabolites in disease processes. In this Review, the methodological aspects related to metabolomic profiling and any potential links between metabolomics and the genetics of some of the most common rheumatic diseases are described. Links between metabolomics, genetics and emerging fields such as the gut microbiome and proteomics are also discussed.
Pelvic inflammatory disease and upper genital tract infection describe inflammatory changes in the upper female genital tract of any combination: endometritis, salpingitis, tubo-ovarian abscess and peritonitis in the small pelvis. In most cases the infection is ascending, Chlamydia trachomatis and Neisseria gonorrhoeae are common with increasing incidence. The spectrum ranges from subclinical, asymptomatic infection to severe, life-threatening illness. Antibiotic treatment should be initiated promptly and must cover a broad spectrum of germs. Surgical treatment is necessary in cases of failure of antibiotic treatment and in cases with persisting symptoms after antibiotic treatment. Pelvic inflammatory diseases are one of the main causes of tubal sterility, ectopic pregnancies and chronic abdominal pain.
Eriksson, J K; Askling, J; Arkema, E V
New therapeutic options are constantly emerging for the treatment of rheumatic diseases. To evaluate the safety and efficacy of newly introduced anti-rheumatic treatment alternatives, registers are an important source of information. The Swedish Rheumatology Quality Register (SRQ) collects clinical data on patients with rheumatoid arthritis, as well as other rheumatic diseases, and may be enriched with data on comorbid conditions, prescription drug dispensings, and mortality from national data sources in Sweden. In this setting, many different outcomes can be investigated over a long period of time in a diverse population of patients recruited in daily clinical practice.
Gils, Ann; Bertolotto, Antonio; Mulleman, Denis; Bejan-Angoulvant, Theodora; Declerck, Paul J
Biopharmaceuticals are primarily therapeutic proteins developed to perform specific functions by acting on the disease pathophysiology. Compared to low molecular chemically synthesized drugs, production of biopharmaceuticals is much more complex and routes of administration and pharmacokinetics differ. Biopharmaceuticals are blockbusters in the treatment of inflammatory diseases such as psoriasis, multiple sclerosis, rheumatic diseases, and inflammatory bowel diseases, and the introduction of these drugs has revolutionized treatment. Disadvantages include their high costs and the fact that they can evoke antidrug antibodies leading to decreased efficacy. Treatment can be optimized through the development of dosing algorithms and cost can be reduced by biosimilars, after a comparable biological activity, safety, and efficacy have been demonstrated.
Del Río Nájera, Danyella; González-Chávez, Susana Aideé; Quiñonez-Flores, Celia María; Peláez-Ballestas, Ingris; Hernández-Nájera, Norma; Pacheco-Tena, César F
Rheumatic diseases (RDs) represent a global problem for health care systems and patients. Community Oriented Program for Control of Rheumatic Diseases (COPCORD) is a low-cost screening tool for detecting musculoskeletal (MSK) pain and RDs. The aim of this study was to examine the pattern of MSK pain and RDs in clinic population in Chihuahua City, Mexico. A cross-sectional study was conducted in 7 primary health clinics using the COPCORD methodology in subjects older than 18 years. People with MSK pain not induced by trauma (positive cases) were evaluated by primary care physicians and rheumatologists. The study included 1006 individuals with a mean age of 46.0 (SD, 15.8) years; 751 (74.7%) were women. Musculoskeletal pain in the previous 7 days was reported by 571 individuals (56.75%; 95% confidence interval [CI], 53.8%-60.1%), and 356 cases (35.4%; 95% CI, 32.5%-38.4%) were COPCORD positive. The mean pain intensity in visual analog scale was 6.62 (SD, 2.4). The most common painful joint was the knee (54.7%; 95% CI, 51.1%-59.0%). Two hundred eighty subjects with MSK pain (49.0%) previously sought medical attention, and 375 (65.7%) were under treatment. Functional impairment was reported by 69.8% of the COPCORD-positive subjects. The prevalence of RDs was 21.4% (95% CI, 18.9%-23.8%). The most prevalent disease was osteoarthritis (10.3%; 95% CI, 8.6%-12.4%), followed by regional pain syndromes (5.5%; 95% CI, 4.1%-7.0%), rheumatoid arthritis (1.4%; 95% CI, 0.8%-2.2%), and mechanical low-back pain (1.4%; 95% CI, 0.7%-2.2%). Musculoskeletal pain is an important problem that affects our community. The data provided in this study will be presented to the local authorities to help in the development of prevention strategies.
Introduction Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the US, and is diagnosed in approximately 1% of women aged 16 to 45 years consulting their GP in England and Wales. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: How do different antimicrobial regimens compare when treating women with confirmed pelvic inflammatory disease? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up to date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 13 RCTs or systematic reviews of RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, different durations, different regimens) and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk). PMID:24330771
Ross, Jonathan D C
Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the US, and is diagnosed in approximately 1% of women aged 16 to 45 years consulting their GP in England and Wales. We conducted a systematic review and aimed to answer the following clinical questions: How do different antimicrobial regimens compare when treating women with confirmed pelvic inflammatory disease? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up to date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 13 RCTs or systematic reviews of RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, different durations, different regimens) and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk).
Mizeva, Irina; Makovik, Irina; Dunaev, Andrey; Krupatkin, Alexander; Meglinski, Igor
Laser Doppler flowmetry (LDF) has been applied for the assessment of variation in blood microflows in patients with rheumatic diseases and healthy volunteers. Oscillations of peripheral blood microcirculation observed by LDF have been analyzed utilizing a wavelet transform. A higher amplitude of blood microflow oscillations has been observed in a high frequency band (over 0.1 Hz) in patients with rheumatic diseases. Oscillations in the high frequency band decreased in healthy volunteers in response to the cold pressor test, whereas lower frequency pulsations prevailed in patients with rheumatic diseases. A higher perfusion rate at normal conditions was observed in patients, and a weaker response to cold stimulation was observed in healthy volunteers. Analysis of blood microflow oscillations has a high potential for evaluation of mechanisms of blood flow regulation and diagnosis of vascular abnormalities associated with rheumatic diseases.
Yiu, Kai-Hang; Tse, Hung-Fat; Mok, Mo-Yin; Lau, Chak-Sing
Rheumatic diseases are associated with high cardiovascular morbidity and mortality. Considerable differences exist in the frequency of cardiovascular disease (CVD) risk factors and events among people of different ethnic origins, but little is known of the ethnic variations in the relative distribution of CVD risk factors and the degree of atherosclerosis in patients with rheumatic diseases. Understanding this variation will provide insight into the underlying pathogenesis of CVD in patients with rheumatic diseases, and aid in future studies of the detection and management of this complication. In general, although Asian patients seem to have fewer background CVD risk factors and are less affected by metabolic syndrome (MetS) than their non-Asian counterparts, those with rheumatic disease are equally as susceptible to CVD. Furthermore, it seems that systemic inflammation and mechanisms that do not involve conventional CVD risk factors and MetS have an important role in the development of atherosclerosis in patients with rheumatic diseases. Here we examine the frequency of conventional CVD risk factors and the prevalence of MetS in both Asian and non-Asian patients with selected rheumatic diseases. We also discuss the burden of CVD, as evaluated using various surrogate markers in these patients, and their overall CVD mortality rate.
Teles, Kaian Amorim; Medeiros-Souza, Patrícia; Lima, Francisco Aires Correa; Araújo, Bruno Gedeon de; Lima, Rodrigo Aires Correa
Cyclophosphamide (CPM) is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy (pre-ChT), administration of cyclophosphamide, and post-chemotherapy (post-ChT), taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare-but serious-side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.
Ermann, Joerg; Rao, Deepak A.; Teslovich, Nikola C.; Brenner, Michael B.; Raychaudhuri, Soumya
Biomarkers are needed to guide treatment decisions for patients with rheumatic diseases. Although the phenotypic and functional analysis of immune cells is an appealing strategy for understanding immune-mediated disease processes, immune cell profiling currently has no role in clinical rheumatology. New technologies, including mass cytometry, gene expression profiling by RNA sequencing (RNA-seq) and multiplexed functional assays, enable the analysis of immune cell function with unprecedented detail and promise not only a deeper understanding of pathogenesis, but also the discovery of novel biomarkers. The large and complex data sets generated by these technologies—big data—require specialized approaches for analysis and visualization of results. Standardization of assays and definition of the range of normal values are additional challenges when translating these novel approaches into clinical practice. In this Review, we discuss technological advances in the high-dimensional analysis of immune cells and consider how these developments might support the discovery of predictive biomarkers to benefit the practice of rheumatology and improve patient care. PMID:26034835
Heijstek, M W; Ott de Bruin, L M; Bijl, M; Borrow, R; van der Klis, F; Koné-Paut, I; Fasth, A; Minden, K; Ravelli, A; Abinun, M; Pileggi, G S; Borte, M; Wulffraat, N M
Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.
Vasile, Massimiliano; Corinaldesi, Clarissa; Antinozzi, Cristina; Crescioli, Clara
A large body of evidence highlights the role for vitamin D deficiency/insufficiency in rheumatic diseases, a group of different pathologies mostly of autoimmune origin. Vitamin D and vitamin D receptor agonists exquisitely modulate the immune system against over-reactivity towards tolerance; on this basis, vitamin D could be a good therapeutic candidate to control autoimmune processes in rheumatic diseases. Similarly, to other autoimmune pathologies, rheumatic diseases show a significant female bias. This sexual dimorphism seems, in part, to rely on the different sex hormone-induced regulation on male and female immune systems. Females, in fact, retain greater immune reactivity and competence likely due to estrogens, which, at variance with androgens, are associated with a greater resilience to infections but also to a higher risk for autoimmunity. In this scenario, there is growing interest on vitamin D supplementation for prevention or therapy in rheumatic diseases in relation to gender and sexual hormones. The purpose of the review is to overview vitamin D status in rheumatic diseases, related to gender and sex hormones. In particular, the main vitamin D immunoregulatory properties are summarized with some sex hormone-driven immune activities, in females and males immune systems. Topics onto vitamin D receptor agonists as potential therapeutic agents in rheumatic disease are addressed, especially in view of the role of vitamin D inadequacy in the pathogenesis of rheumatic diseases. So far, further clinical and basic studies should be encouraged to confirm the high potential power of vitamin D receptor agonists as novel pharmacological tools in rheumatic diseases particularly in light of personalized gender-related therapeutic strategies.
Beltrame, Marcia Holsbach; Catarino, Sandra Jeremias; Goeldner, Isabela; Boldt, Angelica Beate Winter; de Messias-Reason, Iara José
The innate immune system is the first line of host defense against infection and is comprised of humoral and cellular mechanisms that recognize potential pathogens within minutes or hours of entry. The effector components of innate immunity include epithelial barriers, phagocytes, and natural killer cells, as well as cytokines and the complement system. Complement plays an important role in the immediate response against microorganisms, including Streptococcus sp. The lectin pathway is one of three pathways by which the complement system can be activated. This pathway is initiated by the binding of mannose-binding lectin (MBL), collectin 11 (CL-K1), and ficolins (Ficolin-1, Ficolin-2, and Ficolin-3) to microbial surface oligosaccharides and acetylated residues, respectively. Upon binding to target molecules, MBL, CL-K1, and ficolins form complexes with MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2), which cleave C4 and C2 forming the C3 convertase (C4b2a). Subsequent activation of complement cascade leads to opsonization, phagocytosis, and lysis of target microorganisms through the formation of the membrane-attack complex. In addition, activation of complement may induce several inflammatory effects, such as expression of adhesion molecules, chemotaxis and activation of leukocytes, release of reactive oxygen species, and secretion of cytokines and chemokines. In this chapter, we review the general aspects of the structure, function, and genetic polymorphism of lectin-pathway components and discuss most recent understanding on the role of the lectin pathway in the predisposition and clinical progression of Rheumatic Fever. PMID:25654073
Taspinar, O; Aydın, T; Celebi, A; Keskin, Y; Yavuz, S; Guneser, M; Camli, A; Tosun, M; Canbaz, N; Gok, M
The aim of this study was to evaluate the effects of calisthenic exercises on psychological status in patients with ankylosing spondylitis (AS) and multiple sclerosis (MS). This study comprised 40 patients diagnosed with AS randomized into two exercise groups (group 1 = hospital-based, group 2 = home-based) and 40 patients diagnosed with MS randomized into two exercise groups (group 1 = hospital-based, group 2 = home-based). The exercise programme was completed by 73 participants (hospital-based = 34, home-based = 39). Mean age was 33.75 ± 5.77 years. After the 8-week exercise programme in the AS group, the home-based exercise group showed significant improvements in erythrocyte sedimentation rates (ESR). The hospital-based exercise group showed significant improvements in terms of the Bath AS Metrology Index (BASMI) and Hospital Anxiety and Depression Scale-Anxiety (HADS-A) scores. After the 8-week exercise programme in the MS group, the home-based and hospital-based exercise groups showed significant improvements in terms of the 10-m walking test, Berg Balance Scale (BBS), HADS-A, and MS international Quality of Life (MusiQoL) scores. There was a significant improvement in the hospital-based and a significant deterioration in the home-based MS patients according to HADS-Depression (HADS-D) score. The positive effects of exercises on neurologic and rheumatic chronic inflammatory processes associated with disability should not be underestimated.
Porta, Francesco; Radunovic, Goran; Vlad, Violeta; Micu, Mihaela C; Nestorova, Rodina; Petranova, Tzvetanka; Iagnocco, Annamaria
The use of Doppler techniques, including power, colour and spectral Doppler, has greatly increased in rheumatology in recent years. This is due to the ability of Doppler US (DUS) to detect pathological vascularization within joints and periarticular soft tissues, thereby demonstrating the presence of active inflammation, which has been reported to be correlated with the local neo-angiogenesis. In synovitis, DUS showed a high correlation with histological and MRI findings, thus it is considered a valid tool to detect pathological synovial vascularization. Moreover, it is more sensitive than clinical examination in detecting active joint inflammation and in the evaluation of response to treatment. In addition, DUS may be considered as a reference imaging modality in the assessment of enthesitis, MRI being not sensitive and histology not feasible. Moreover, it has been demonstrated to be able to detect changes in asymptomatic enthesis. In conclusion, DUS is a useful and sensitive tool in the evaluation and monitoring of active inflammation. Its widespread use in clinical rheumatological practice is recommended. The aim of this article is to review the current literature about the role of DUS in rheumatic diseases, analysing its validity, reliability and feasibility.
Evans, Christopher H; Ghivizzani, Steven C; Robbins, Paul D
During the decade since the launch of Arthritis Research, the application of gene therapy to the rheumatic diseases has experienced the same vicissitudes as the field of gene therapy as a whole. There have been conceptual and technological advances and an increase in the number of clinical trials. However, funding has been unreliable and a small number of high-profile deaths in human trials, including one in an arthritis gene therapy trial, have provided ammunition to skeptics. Nevertheless, steady progress has been made in a number of applications, including rheumatoid arthritis and osteoarthritis, Sjögren syndrome, and lupus. Clinical trials in rheumatoid arthritis have progressed to phase II and have provided the first glimpses of possible efficacy. Two phase I protocols for osteoarthritis are under way. Proof of principle has been demonstrated in animal models of Sjögren syndrome and lupus. For certain indications, the major technological barriers to the development of genetic therapies seem to have been largely overcome. The translational research necessary to turn these advances into effective genetic medicines requires sustained funding and continuity of effort. PMID:19232068
Ramaswamy, Subramanian; Jain, Sandeep; Ravindran, Vinod
Stem cells have their origins in the embryo and during the process of organogenesis, these differentiate into specialized cells which mature to form tissues. In addition, stem cell are characterized by an ability to indefinitely self renew. Stem cells are broadly classified into embryonic stem cells and adult stem cells. Adult stem cells can be genetically reprogrammed to form pluripotent stem cells and exist in an embroyonic like state. In the early phase of embryogenesis, human embryonic stem cells only exist transiently. Adult stem cells are omnipresent in the body and function to regenerate during the process of apoptosis or tissue repair. Hematopoietic stem cells (HSC) are adult stem cells that form blood and immune cells. Autoimmune responses are sustained due to the perennial persistence of tissue self autoantigens and/or auto reactive lymphocytes. Immune reset is a process leading to generation of fresh self-tolerant lymphocytes after chemotherapy induced elimination of self or autoreactive lymphocytes. This forms the basis for autologous HSC transplantation (HSCT). In the beginning HSCT had been limited to refractory autoimmune rheumatic diseases (AIRD) due to concern about transplant related mortality and morbidity. However HSCT for AIRD has come a long way with better understanding of patient selection, conditioning regime and supportive care. In this narrative review we have examined the available literature regarding the HSCT use in AIRD. PMID:27011918
Chow, S K; Yeap, S S; Goh, E M L; Veerapen, K; Lim, K K T
This was a prospective survey using a standard questionnaire to determine the prevalence of use of oral traditional medicine and food supplements among patients with rheumatic diseases. Among the 141 patients surveyed, we found that 69% of the patients were consuming food supplements, 35% were using traditional medicine and 45% had used traditional medicine at some time or other. Females were more likely to use food supplements (P < 0017); especially among those with higher education (p < 0.036). There was no statistical difference between those who had ever consumed compared to those who never used traditional medicines. The Chinese were more likely than others to be using traditional medicine (p < 0.007). Vitamin C and B were the most commonly used food supplements. More than two thirds of the patients obtained their traditional medicine from non-medical personnel. More than half of them used 2 or more types of traditional medicine for more than two months. Spending on traditional medicine was noted to be modest with 73% spending less than one hundred ringgit a month for their traditional treatment. Doctors need to be aware of the possible interactions between these 'self-medications' and the conventionally prescribed medication.
Evans, Christopher H; Ghivizzani, Steven C; Robbins, Paul D
During the decade since the launch of Arthritis Research, the application of gene therapy to the rheumatic diseases has experienced the same vicissitudes as the field of gene therapy as a whole. There have been conceptual and technological advances and an increase in the number of clinical trials. However, funding has been unreliable and a small number of high-profile deaths in human trials, including one in an arthritis gene therapy trial, have provided ammunition to skeptics. Nevertheless, steady progress has been made in a number of applications, including rheumatoid arthritis and osteoarthritis, Sjögren syndrome, and lupus. Clinical trials in rheumatoid arthritis have progressed to phase II and have provided the first glimpses of possible efficacy. Two phase I protocols for osteoarthritis are under way. Proof of principle has been demonstrated in animal models of Sjögren syndrome and lupus. For certain indications, the major technological barriers to the development of genetic therapies seem to have been largely overcome. The translational research necessary to turn these advances into effective genetic medicines requires sustained funding and continuity of effort.
Pelvic inflammatory disease is a polymicrobial infection of the upper genital tract. It primarily affects young, sexually active women. The diagnosis is made clinically; no single test or study is sensitive or specific enough for a definitive diagnosis. Pelvic inflammatory disease should be suspected in at-risk patients who present with pelvic or lower abdominal pain with no identified etiology, and who have cervical motion, uterine, or adnexal tenderness. Chlamydia trachomatis and Neisseria gonorrhoeae are the most commonly implicated microorganisms; however, other microorganisms may be involved. The spectrum of disease ranges from asymptomatic to life-threatening tubo-ovarian abscess. Patients should be treated empirically, even if they present with few symptoms. Most women can be treated successfully as outpatients with a single dose of a parenteral cephalosporin plus oral doxycycline, with or without oral metronidazole. Delay in treatment may lead to major sequelae, including chronic pelvic pain, ectopic pregnancy, and infertility. Hospitalization and parenteral treatment are recommended if the patient is pregnant, has human immunodeficiency virus infection, does not respond to oral medication, or is severely ill. Strategies for preventing pelvic inflammatory disease include routine screening for chlamydia and patient education.
Introduction Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the USA and is diagnosed in almost 2% of women aged 16 to 45 years consulting their GP in England and Wales. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment compared with treatment delayed until the results of microbiological investigations are known? How do different antimicrobial regimens compare? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found nine systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, empirical treatment, treatment guided by test results, different durations, outpatient, inpatient), and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk). PMID:19450319
Waldburger, Jean M; Firestein, Gary S
Advances in our understanding of the cellular and molecular mechanisms in rheumatic disease fostered the advent of the targeted therapeutics era. Intense research activity continues to increase the number of potential targets at an accelerated pace. In this review, examples of promising targets and agents that are at various stages of clinical development are described. Cytokine inhibition remains at the forefront with the success of tumor necrosis factor blockers, and biologics that block interleukin-6 (IL-6), IL-17, IL-12, and IL-23 and other cytokines are on the horizon. After the success of rituximab and abatacept, other cell-targeted approaches that inhibit or deplete lymphocytes have moved forward, such as blocking BAFF/BLyS (B-cell activation factor of the tumor necrosis factor family/B-lymphocyte stimulator) and APRIL (a proliferation-inducing ligand) or suppressing T-cell activation with costimulation molecule blockers. Small-molecule inhibitors might eventually challenge the dominance of biologics in the future. In addition to plasma membrane G protein-coupled chemokine receptors, small molecules can be designed to block intracellular enzymes that control signaling pathways. Inhibitors of tyrosine kinases expressed in lymphocytes, such as spleen tyrosine kinase and Janus kinase, are being tested in autoimmune diseases. Inactivation of the more broadly expressed mitogen-activated protein kinases could suppress inflammation driven by macrophages and mesenchymal cells. Targeting tyrosine kinases downstream of growth factor receptors might also reduce fibrosis in conditions like systemic sclerosis. The abundance of potential targets suggests that new and creative ways of evaluating safety and efficacy are needed. PMID:19232066
Wang, Lan; Wu, Long-Fei; Lu, Xin; Mo, Xing-Bo; Tang, Zai-Xiang; Lei, Shu-Feng; Deng, Fei-Yan
Objective Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested. Methods We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis. Results We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation. Conclusion The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases. PMID:26352601
Naim, M; Tjipta, G D; Siregar, A A; Halim, S
A retrospective study on rheumatic fever and rheumatic heart disease in children was conducted at the Department of Child Health, Dr. Pirngadi Hospital Medan, during 1983-1985. The patients consisted of 43 females and 30 males. Most of the patients were over 12 years of age. Of the 73 patients there were 60 patients (82.19%) accompanied by valvular disorders. The most frequent major criteria of Jones found in this study were carditis and polyarthritis. Thirty one patients (42.46%) had functional status (NYHA) of grade II-IV, and 43 patients (58.90%) had cardiomegaly. The major ECG findings were enlargement of the atria or ventricles and first degree AV block. Compliance was only achieved in 25 (34.24%) cases. Rheumatic fever and rheumatic heart disease still remain a challenge for the medical professionals to cope with in the region.
Burguera, Elena Fernandez; Meijide-Failde, Rosa; Blanco, Francisco J
Rheumatoid arthritis (RA) and osteoarthritis (OA) are widespread rheumatic diseases characterized by persistent inflammation and joint destruction. Hydrogen sulfide (H2S) is an endogenous gas with important physiologic functions in the brain, vasculature and other organs. Recent studies have found H2S to be a mediator in inflammatory joint diseases. H2S exhibited anti-inflammatory, anti-catabolic and/or anti-oxidant effects in rodent models of acute arthritis and in in vitro models using human synoviocytes and articular chondrocytes from RA and OA tissues. These findings suggest that exogenous supplementation of H2S may provide a viable therapeutic option for these diseases. The earliest studies used fast-dissolving salts, such as NaSH, but GYY4137, which produces H2S more physiologically, shortly appeared. More recently still, new H2S-forming compounds that target mitochondria have been synthesized. These compounds open exciting opportunities for investigating the role of H2S in cell bioenergetics, typically altered in arthritides. Positive results have been also obtained when H2S is administered as a sulphurous water bath, an option meriting further study. This review summarizes the recent literature concerning H2S and inflammatory joint diseases, highlighting relevant developments.
Yin, Kai; Agrawal, Devendra K
Beyond its critical function in calcium homeostasis, vitamin D has recently been found to play an important role in the modulation of the immune/inflammation system via regulating the production of inflammatory cytokines and inhibiting the proliferation of proinflammatory cells, both of which are crucial for the pathogenesis of inflammatory diseases. Several studies have associated lower vitamin D status with increased risk and unfavorable outcome of acute infections. Vitamin D supplementation bolsters clinical responses to acute infection. Moreover, chronic inflammatory diseases, such as atherosclerosis-related cardiovascular disease, asthma, inflammatory bowel disease, chronic kidney disease, nonalcoholic fatty liver disease, and others, tend to have lower vitamin D status, which may play a pleiotropic role in the pathogenesis of the diseases. In this article, we review recent epidemiological and interventional studies of vitamin D in various inflammatory diseases. The potential mechanisms of vitamin D in regulating immune/inflammatory responses in inflammatory diseases are also discussed. PMID:24971027
Straub, Rainer H.; Schradin, Carsten
It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3–8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting—cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483
Ruiz-Romero, Cristina; Calamia, Valentina; Albar, Juan Pablo; Casal, José Ignacio; Corrales, Fernando J; Fernández-Puente, Patricia; Gil, Concha; Mateos, Jesús; Vivanco, Fernando; Blanco, Francisco J
The Spanish Chromosome 16 consortium is integrated in the global initiative Human Proteome Project, which aims to develop an entire map of the proteins encoded following a gene-centric strategy (C-HPP) in order to make progress in the understanding of human biology in health and disease (B/D-HPP). Chromosome 16 contains many genes encoding proteins involved in the development of a broad range of diseases, which have a significant impact on the health care system. The Spanish HPP consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. Proteomics strategies have enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. In this manuscript we describe how the Spanish HPP-16 consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. We show how the Proteomic strategy has enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. This article is part of a Special Issue entitled: HUPO 2014. Copyright © 2015 Elsevier B.V. All rights reserved.
Inflammatory bowel disease (IBD) is the term used for a group of diseases with yet unknown etiology, prevalence of which is increasing almost everywhere in the world. The disease was almost non-existent four decades ago in the east, including the middle-east, while now a days it is seen more and more. In addition to the increasing prevalence, our knowledge about its pathogenesis, clinical course, diagnosis, and treatment has changed dramatically over the past couple of decades. This has changed our concept of this group of diseases, their diagnosis, treatment, and treatment goals. Considering the vast literature on the subject, it is timely to review major topics in IBD with a look on the regional progress and knowledge as well. This essay is aimed to cover this task. PMID:24829639
Corsiero, Elisa; Bombardieri, Michele; Manzo, Antonio; Bugatti, Serena; Uguccioni, Mariagrazia; Pitzalis, Costantino
A sizeable subset of patients with the two most common organ-specific rheumatic autoimmune diseases, rheumatoid arthritis (RA) and Sjögren's syndrome (SS) develop ectopic lymphoid structures (ELS) in the synovial tissue and salivary glands, respectively. These structures are characterized by perivascular (RA) and periductal (SS) clusters of T and B lymphocytes, differentiation of high endothelial venules and networks of stromal follicular dendritic cells (FDC). Accumulated evidence from other and our group demonstrated that the formation and maintenance of ELS in these chronic inflammatory conditions is critically dependent on the ectopic expression of lymphotoxins (LT) and lymphoid chemokines CXCL13, CCL19, CCL21 and CXCL12. In this review we discuss recent advances highlighting the cellular and molecular mechanisms, which regulate the formation of ELS in RA and SS, with particular emphasis on the role of lymphoid chemokines. In particular, we shall focus on the evidence that in the inflammatory microenvironment of the RA synovium and SS salivary glands, several cell types, including resident epithelial, stromal and endothelial cells as well as different subsets of infiltrating immune cells, have been shown to be capable of producing lymphoid chemokines. Finally, we summarize accumulating data supporting the conclusion that ELS in RA and SS represent functional niches for B cells to undergo affinity maturation, clonal selection and differentiation into plasma cells autoreactive against disease-specific antigens, thus contributing to humoral autoimmunity over and above that of secondary lymphoid organs.
Hematopoietic stem cells (HSC) are increasingly available as an alternative to whole marrow aspirate for bone marrow transplantation (BMT). They may be derived from an HLA matched individual (allogeneic) or from the patient (autologous). Allogeneic BMT is associated with a 15 to 35% mortality, largely due to graft versus host disease. Autologous HSC are used to rescue the patient after severe immunosuppression, and the transplant related mortality is 3 to 5%. The opportunity to ablate severe autoimmune disease with increased safety is particularly attractive for necrotizing vasculitides, polymyositis/dermatomyositis, primary Sjögren's syndrome, systemic juvenile arthritis, relapsing polychondritis, and Behçet's disease, where correct selection of cases would ensure an acceptable benefit/risk ratio. Rheumatoid arthritis (RA), psoriasis associated arthritis (PsA) and some non-rheumatic diseases such as inflammatory bowel disease (IBD), multiple sclerosis, and type 1 diabetes mellitus may also be candidates, but careful selection of patients with a poor prognosis is necessary. There are allogeneic BMT data from patients with aplastic anemia or leukemia and concurrent RA, PsA, and IBD and also autologous HSC BMT data from animal models to support the concept of cure. Patient studies should proceed using recently published protocol guidelines and centralized data collection.
Martins, Carlo de Oliveira; Demarchi, Lea; Ferreira, Frederico Moraes; Pomerantzeff, Pablo Maria Alberto; Brandao, Carlos; Sampaio, Roney Orismar; Spina, Guilherme Sobreira; Kalil, Jorge; Cunha-Neto, Edecio
Autoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases. PMID:28121998
Martins, Carlo de Oliveira; Demarchi, Lea; Ferreira, Frederico Moraes; Pomerantzeff, Pablo Maria Alberto; Brandao, Carlos; Sampaio, Roney Orismar; Spina, Guilherme Sobreira; Kalil, Jorge; Cunha-Neto, Edecio; Guilherme, Luiza
Autoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases.
Gündogdu, Fuat; Islamoglu, Yahya; Pirim, Ibrahim; Gurlertop, Yekta; Dogan, Hasan; Arslan, Sakir; Sevimli, Serdar; Aksakal, Enbiya; Senocak, Huseyin
Rheumatic heart disease (RHD) is often preceded by rheumatic fever (RF). The disease is a multisystem inflammatory condition that develops as a sequel to untreated throat infection by group A beta-hemolytic streptococci. Several studies have suggested that genetic susceptibility to RHD may be linked to human leukocyte antigen (HLA) class II alleles. The study aim was to investigate the association between RHD and the antigens HLA-A, -B, -C, -DR and -DQ profile in RHD patients in eastern Turkey. A case-control study was conducted which included 85 unrelated patients with RHD, and 85 control subjects. The diagnosis was supported by echocardiography and histories of RHD of those patients who underwent valve replacement. The association of class I and class II HLA antigens was examined in RHD and control subjects using a sequence-specific primer (SSP) method. The phenotypes HLA-B51, -Cw*4 and -DRB1*01 were encountered in significantly lower frequencies in patients with RHD compared to the control population (p <0.05, p <0.05, p <0.05, respectively). There was also a significant increase in antigen frequency of HLA-DQB1*08 in RHD patients compared to controls (p <0.005). Among the studied population, the results suggested that susceptibility to RHD was HLA-related, with HLA-DQB1*08 most likely influencing the occurrence of the condition. HLA-B51, -Cw*4 and -DRB1*01 appeared to be more common in control subjects.
Cohen, Ezra M; Morley-Fletcher, Alessio; Mehta, Darshan H; Lee, Yvonne C
To assess the quality of evidence for the effects of psychosocial therapies on pain and function in children with rheumatic diseases. We conducted a literature search of MEDLINE and PsycINFO for randomized clinical trials of psychosocial interventions for pain and disability in children with rheumatic diseases from January 1969 to September 2015. Studies with a sample size less than 10 subjects were excluded. Study quality was assessed using the Jadad score. Five articles met inclusion criteria, for a total of 229 patients, aged 5 to 18 years. Two studies included children with fibromyalgia. Three studies included children with juvenile arthritis. Neither study in fibromyalgia reported the statistical significance of immediate between-group pre-post changes in functioning or pain. One study examining the effects of an internet-based psychosocial intervention in children with juvenile arthritis reported significant differences in post-intervention pain scores (p = 0.03). However, 2 studies did not show improvements in pain scores among children with juvenile arthritis treated with psychosocial interventions vs. a wait-list control or vs. an active control (massage). No studies reported significant between-group differences for functional outcomes in children with juvenile arthritis. The available data were limited by the scarcity of randomized trials. Definite conclusions about the immediate effect of psychosocial interventions on pain and function in children with fibromyalgia could not be made because between-group comparisons of post-treatment change scores were not reported. For children with juvenile inflammatory arthritis, results of between-group comparisons for pain differed across studies, and analyses examining disability revealed no significant differences between groups.
Bertaina, Geneviève; Rouchon, Bernard; Huon, Bertrand; Guillot, Nina; Robillard, Corinne; Noël, Baptiste; Nadra, Marie; Tribouilloy, Christophe; Marijon, Eloi; Jouven, Xavier; Mirabel, Mariana
The advent of systematic screening for rheumatic heart disease (RHD) by echocardiography in endemic regions has led to a new entity: borderline RHD. The pathogenicity and natural history of borderline RHD needs to be addressed. The aim of this study was to assess the outcomes of children detected by echocardiography as having borderline RHD. Schoolchildren in 4th grade (i.e., aged 9-10years) who were prospectively echo-screened for RHD (2012-2014) in Nouméa, New Caledonia, were asked to participate. Children with borderline RHD according to consistent independent review by two cardiologists were included and followed-up in 2015. Among the 8684 schoolchildren screened, 49 were diagnosed with borderline RHD according to the Cardiologist clinically involved in the child's management plan. After independent review by two cardiologists, 25 children were consistently diagnosed with borderline RHD and included in the follow-up study. Overall, inter-observer agreement was moderate with diagnostic kappa values of 0.63 (95% CI 0.45-0.78). After a median follow-up of 23months (IQR (20.5-33.0), 15 children (60.0%) had stability of valvular lesions, 8 (32.0%) had normal findings according to the WHF criteria. Two children (8.0%) had definite RHD on the follow-up echocardiogram, but no clinical events or audible pathological murmur during the study period. No factor could be identified as prognostic of either stability or progression. Borderline RHD diagnosed by systematic screening in high-risk populations remains mostly unchanged at 2years follow-up. Diagnosis of borderline RHD may require two reviewers for consistency. Copyright © 2016. Published by Elsevier Ireland Ltd.
Ehlebracht-König, I; Bönisch, A
A one-week booster group treatment in rheumatic diseases (rheumatoid arthritis, spondylarthropathies, fibromyalgia) was developed in order to stabilize rehabilitation effects after medical rehabilitation. The program took place in an inpatient setting 3 - 5 months after rehabilitation, aimed at refreshing and deepening already learnt contents as well as teaching new subjects (e. g. about dietetics). Training and educational elements are given priority in this concept. A total of 140 patients participated in 19 booster weeks. At the end of each booster week the acceptance was assessed by questionnaire and in a round-table discussion. Comprehensibility and group atmosphere were judged very positively. The course was also considered very helpful, helpfulness being rated with marks about 2 (1 = very helpful, 6 = not at all helpful). Participants especially appreciated the course's framework as a group setting emphasising the exchange of experience with co-patients. At the same time, however, participants wished more individualized treatment such as physiotherapy or massage. With regard to the quantity of the various therapy elements, participants would have preferred more traditional spa therapy, more medical treatment by a physician, more group physiotherapy and sports. They would also have liked more breaks. In general fewer psychological elements, less discussion and reflection but more physical activity was wished for. Little difference was found between the various diagnoses, but the program was rated slightly more positively by the patients with spondylarthropathies. Overall, the great number of people participating in the program and their acceptance of the booster week are positive. Patients appreciated the group setting and the possibilities of exchanging experience on a high level. But it was difficult to change patients' traditional expectations concerning medical rehabilitation to a behaviour-orientated course like ours. It is worth thinking about whether
Avina-Zubieta, J; Galindo-Rodriguez, G.; Newman, S.; Suarez-Almazor, M.; Russell, A.
/possible retinopathy was found. Therefore, we propose a careful baseline ophthalmological evaluation by an expert and then one or every two years if proper doses are used. Keywords: antimalarial drugs; long term effectiveness; efficacy; toxicity; rheumatic diseases PMID:9893568
Kool, Marianne B; Geenen, Rinie
Rheumatic diseases affect about 20% of the population, leading to common symptoms such as joint problems, pain, fatigue, and stiffness. Loneliness is prevalent in individuals with rheumatic diseases. This could be due to not receiving social support and being stigmatized and invalidated, which might be most common in fibromyalgia, a rheumatic disease that lacks medical evidence. The aim of this study was to compare loneliness in distinct rheumatic diseases and to examine the association of loneliness with social support and invalidation. Participants were 927 patients with ankylosing spondylitis (n = 152), fibromyalgia (n = 341), osteoarthritis (n = 150), rheumatoid arthritis (n = 171), or systemic diseases (n = 113). They completed online questionnaires including an 11-point Likert scale assessing loneliness, the Illness Invalidation Inventory (3*1; Kool et al., 2010), and the Social Support Survey (SSS; De Boer, Wijker, Speelman, & De Haes, 1996; Sherbourne & Stewart, 1991). Patients with fibromyalgia experienced significantly more loneliness than patients with ankylosing spondylitis and patients with rheumatoid arthritis. Besides being younger, having lower education, and not working, in multiple regression analyses both lack of social support and invalidation were independently correlated with loneliness. This suggests that to decrease loneliness, therapeutic attention should be given to both increasing social support as well as decreasing invalidation in patients with rheumatic diseases, especially in patients with fibromyalgia.
Zhou, Ning; Chen, Wei-xing; Chen, Shao-hua; Xu, Cheng-fu; Li, You-ming
Objective: Inflammatory bowel diseases (IBDs) are idiopathic, chronic, and inflammatory intestinal disorders. The two main types, ulcerative colitis (UC) and Crohn’s disease (CD), sometimes mimic each other and are not readily distinguishable. The purpose of this study was to present a series of hospitalized cases, which could not initially be classified as a subtype of IBD, and to try to note roles of the terms indeterminate colitis (IC) and inflammatory bowel disease unclassified (IBDU) when such a dilemma arises. Methods: Medical records of 477 patients hospitalized due to IBD, during the period of January 2002 to April 2009, were retrospectively studied in the present paper. All available previous biopsies from endoscopies of these patients were reanalyzed. Results: Twenty-seven of 477 IBD patients (5.7%) had been initially diagnosed as having IBDU. Of them, 23 received colonoscopy and histological examinations in our hospital. A total of 90% (9/10) and 66.7% (4/6) of patients, respectively, had a positive finding via wireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE). The barium-swallow or small bowel follow-through (SBFT) was performed on 11 patients. Positive changes were observed under computer tomographic (CT) scanning in 89.5% (17/19) of patients. Reasonable treatment strategies were employed for all patients. Conclusions: Our data indicate that IBDU accounts for 5.7% of initial diagnoses of IBD. The definition of IBDU is valuable in clinical practice. For those who had no clear clinical, endoscopic, histological, or other features affording a diagnosis of either UC or CD, IBDU could be used parenthetically. PMID:21462383
Bharat, A; Xie, F; Baddley, JW; Beukelman, T; Chen, L; Calabrese, L; Delzell, E; Grijalva, CG; Patkar, N; Saag, K; Winthrop, K; Curtis, JR
We conducted a large, population-based study to describe the incidence and risk factors for progressive multifocal leukoencephalopathy (PML) among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS) using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services (CMS) from 2000–2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data >= 6 months prior to PML diagnosis. Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6/100,000 patients). Most PML cases had HIV and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months(all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2/100,000 patients with autoimmune diseases who did not have HIV or malignancy. PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy. PMID:22162369
ETIOLOGY OF DEGENERATIVE JOINT DISEASES: Etiology of degenerative joint diseases is still not clearly understood and there is no specific management for this group of diseases. Various pathological conditions cause damage of the articular cartilage and lead to clinically and radiographically recognized impairment. Biomechanical, metabolic, genetic factors, inflammation and other risk factors contribute to development of osteoarthrosis. PATHOPHYSIOLOGY OF DEGENERATIVE JOINT DISEASES: Osteoarthrosis is characterized by progressive erosion of articular cartilage and bone overgrowth at the joint margins. Cartilage integrity requires balance between synthesis and degradation of matrix components. Chondrocytes react to various mechanical and chemical stresses in order to stabilize and restore the tissue. Failures in stabilizing and restoring the tissue lead to cartilage degeneration that may be irreversibile. For better understanding of conservative management of degenerative joint diseases it is important to know the impact of pathophysiology mechanisms on development of degenerative joint diseases. There is great variability in the rate of progression of erosive processes in articular cartilage in clinical, radiographic signs and course of the disease. This is in relation with many factors, as well as with management and response to therapy. TREATMENT OF DEGENERATIVE JOINT DISEASES: Treatment should vary depending on the severity of disease and patient's expectations and level of activity. Besides analgesic and anti-inflammatory drugs, conventional and not conventional treatment and techniques can be used for management of osteoarthrosis. Physical therapy and exercises are very important for maintaining muscle strength, joint stability and mobility, but should be closely monitored for optimal efficacy.
Amorim, Ana Luiza M; Cabral, Nadia C; Osaku, Fabiane M; Len, Claudio A; Oliveira, Enedina M L; Terreri, Maria Teresa
Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.
Aikawa, Nadia Emi; de Oliveira Twardowsky, Aline; de Carvalho, Jozélio Freire; Silva, Clovis A; Silva, Ivan Leonardo Avelino França e; de Medeiros Ribeiro, Ana Cristina; Saad, Carla Gonçalves Schain; Moraes, Julio César Bertacini; de Toledo, Roberto Acayaba; Bonfá, Eloísa
OBJECTIVE: Immunosuppressed patients are at risk of microsporidiosis, and this parasitosis has an increased rate of dissemination in this population. Our objective was to evaluate the presence of microsporidiosis and other intestinal parasites in rheumatic disease patients undergoing anti-tumor necrosis factor/disease-modifying anti-rheumatic drug treatment. METHODS: Ninety-eight patients (47 with rheumatoid arthritis, 31 with ankylosing spondylitis and 11 with psoriatic arthritis) and 92 healthy control patients were enrolled in the study. Three stool samples and cultures were collected from each subject. RESULTS: The frequency of microsporidia was significantly higher in rheumatic disease patients than in control subjects (36 vs. 4%, respectively; p<0.0001), as well as in those with rheumatic diseases (32 vs. 4%, respectively; p<0.0001), ankylosing spondylitis (45 vs. 4%, respectively; p<0.0001) and psoriatic arthritis (40 vs. 4%, respectively; p<0.0001), despite a similar social-economic class distribution in both the patient and control groups (p = 0.1153). Of note, concomitant fecal leukocytes were observed in the majority of the microsporidia-positive patients (79.5%). Approximately 80% of the patients had gastrointestinal symptoms, such as diarrhea (26%), abdominal pain (31%) and weight loss (5%), although the frequencies of these symptoms were comparable in patients with and without this infection (p>0.05). Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups (p>0.05). The duration of anti-tumor necrosis factor/disease-modifying anti-rheumatic drugs and glucocorticoid use were also similar in both groups. CONCLUSION: We have documented that microsporidiosis with intestinal mucosa disruption is frequent in patients undergoing concomitant anti-tumor necrosis factor/disease-modifying anti-rheumatic drug therapy. Impaired host defenses due to the combination of the underlying disease
Raciborski, Filip; Kłak, Anna; Maślińska, Maria; Gryglewicz, Jerzy
Musculoskeletal pain is a very common complaint, affecting 30–40% of the European population. It is estimated that approximately 400,000 Poles suffer from inflammatory rheumatic diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, and a vast majority of those affected are working-age individuals. Patients with suspected arthritis require prompt diagnosis and treatment, as any delays may result in irreversible joint destruction and disability. Currently in Poland, the lag time between the onset of symptoms and diagnosis is, on average, as much as 35 weeks. In this paper, we review the current state of specialist rheumatology care in Poland and propose a reorganised care model that includes early diagnosis of inflammatory arthritis. The main goal we wish to achieve with our reorganised model is to enhance access to outpatient specialist rheumatology care for patients with suspected arthritis. We believe that our model should make it possible to considerably reduce the lag time between GP referral and the diagnosis and treatment by a rheumatologist to as little as 3 to 4 weeks. This article provides a proposal of changes that would achieve this goal and is a summary of the report published by the Institute of Rheumatology in September 2014. PMID:27407218
Physical activity covers not just sports but also simple everyday movements such as housework, walking and playing. Regular exercise has a great importance in maintaining good health, indeed inactivity is a risk factor for different chronic diseases. Physical exercise can play a crucial role in the treatment of rheumatic diseases, optimizing both physical and mental health, enhancing energy, decreasing fatigue and improving sleep. An exercise program for patients with rheumatic diseases aims to preserve or restore a range of motion of the affected joints, to increase muscle strength and endurance, and to improve mood and decrease health risks associated with a sedentary lifestyle. In this editorial I describe the benefits of the exercise on physical limitations and fatigue in rheumatic diseases that seem to have a short and long-term effectiveness. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords based on the present editorial. PMID:26601057
Loddenkemper, Konstanze; Bohl, Nicole; Perka, Carsten; Burmester, Gerd-Rüdiger; Buttgereit, Frank
Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)
Physical activity covers not just sports but also simple everyday movements such as housework, walking and playing. Regular exercise has a great importance in maintaining good health, indeed inactivity is a risk factor for different chronic diseases. Physical exercise can play a crucial role in the treatment of rheumatic diseases, optimizing both physical and mental health, enhancing energy, decreasing fatigue and improving sleep. An exercise program for patients with rheumatic diseases aims to preserve or restore a range of motion of the affected joints, to increase muscle strength and endurance, and to improve mood and decrease health risks associated with a sedentary lifestyle. In this editorial I describe the benefits of the exercise on physical limitations and fatigue in rheumatic diseases that seem to have a short and long-term effectiveness. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords based on the present editorial.
Soper, David E
Pelvic inflammatory disease (PID) is an infection-caused inflammatory continuum from the cervix to the peritoneal cavity. Most importantly, it is associated with fallopian tube inflammation, which can lead to infertility, ectopic pregnancy, and chronic pelvic pain. The microbial etiology is linked to sexually transmitted microorganisms, including Chlamydia trachomatis, Neisseria gonorrheae, Mycoplasma genitalium, and bacterial vaginosis-associated microorganisms, predominantly anaerobes. Pelvic pain and fever are commonly absent in women with confirmed PID. Clinicians should consider milder symptoms such as abnormal vaginal discharge, metrorrhagia, postcoital bleeding, and urinary frequency as potential symptoms associated with the disease, particularly in women at risk of sexually transmitted infection. The diagnosis of PID is based on the findings of lower genital tract inflammation associated with pelvic organ tenderness. The outpatient treatment of mild-to-moderate PID should include tolerated antibiotic regimens with activity against the commonly isolated microorganisms associated with PID and usually consists of an extended spectrum cephalosporin in conjunction with either doxycycline or azithromycin. Clinically severe PID should prompt hospitalization and imaging to rule out a tuboovarian abscess. Parenteral broad-spectrum antibiotic therapy with activity against a polymicrobial flora, particularly gram-negative aerobes and anaerobes, should be implemented. Screening for and treatment of Chlamydia infection can prevent PID.
Amorim, Ana Luiza M; Cabral, Nadia C; Osaku, Fabiane M; Len, Claudio A; Oliveira, Enedina M L; Terreri, Maria Teresa
Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. ANA was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of ANA-positive patients were diagnosed with rheumatologic autoimmune disieses. Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of ANA positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults. Copyright © 2016. Published by Elsevier Editora Ltda.
Frommer, Klaus W; Schäffler, Andreas; Rehart, Stefan; Lehr, Angela; Müller-Ladner, Ulf; Neumann, Elena
Due to their role in inflammatory metabolic diseases, we hypothesised that free fatty acids (FFA) are also involved in inflammatory joint diseases. To test this hypothesis, we analysed the effect of FFA on synovial fibroblasts (SF), human chondrocytes and endothelial cells. We also investigated whether the toll-like receptor 4 (TLR4), which can contribute to driving arthritis, is involved in FFA signalling. Rheumatoid arthritis SF, osteoarthritis SF, psoriatic arthritis SF, human chondrocytes and endothelial cells were stimulated in vitro with different FFA. Immunoassays were used to quantify FFA-induced protein secretion. TLR4 signalling was inhibited extracellularly and intracellularly. Fatty acid translocase (CD36), responsible for transporting long-chain FFA into the cell, was also inhibited. In rheumatoid arthritis synovial fibroblasts (RASF), FFA dose-dependently enhanced the secretion of the proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, as well as the matrix-degrading enzymes pro-MMP1 and MMP3. The intensity of the response was mainly dependent on the patient rather than on the type of disease. Both saturated and unsaturated FFA showed similar effects on RASF, while responses to the different FFA varied for human chondrocytes and endothelial cells. Extracellular and intracellular TLR4 inhibition as well as fatty acid transport inhibition blocked the palmitic acid-induced IL-6 secretion of RASF. The data show that FFA are not only metabolic substrates but may also directly contribute to articular inflammation and degradation in inflammatory joint diseases. Moreover, the data suggest that, in RASF, FFA exert their effects via TLR4 and require extracellular and intracellular access to the TLR4 receptor complex. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Schett, Georg; Dayer, Jean-Michel; Manger, Bernhard
Interleukin (IL)-1, first described ∼35 years ago as a secreted product of monocytes and neutrophils, refers to IL-1α and IL-1β, two key cytokines in the activation of innate immunity. These cytokines were among the first proteins identified as orchestrators of leukocyte communication, creating the class of secreted products now known as interleukins. The IL-1 family comprises a total of 11 members, including the two activating cytokines IL-1α and IL-1β as well as an inhibitory mediator, the IL-1 receptor antagonist. IL-1 is processed and activated by a caspase-1 dependent mechanism in conjunction with inflammasome assembly, as well as by caspase-1 independent processes that involve neutrophil proteases. Once activated, IL-1α and IL-1β act as potent proinflammatory cytokines at the local level, triggering vasodilatation and attracting monocytes and neutrophils to sites of tissue damage and stress. Importantly, these cytokines are crucial for the induction of matrix enzymes and serve as potent mediators of tissue damage by altering cartilage and bone homeostasis. Systemically, IL-1 cytokines foster the hypothalamic fever response and promote hyperalgesia. Uncontrolled IL-1 activation is a central component of some inflammatory diseases, including rare hereditary syndromes with mutations in inflammasome-associated genes or more frequent diseases such as gout, characterized by neutrophil infiltration and IL-1 activation. Apart from these connections to inflammatory diseases, an important role for IL-1 in inflammatory atherogenesis is also predicted. To date, four potent inhibitors of IL-1 are available for clinical use or in late-stage clinical development, which not only constitute efficacious therapies, but also helped improve our understanding of the role of IL-1 in human disease.
Kaddu-Mukasa, M; Ssekasanvu, E; Ddumba, E; Thomas, D; Katabira, E T
Rheumatic manifestations in HIV are common and sometimes the initial presentation of the disease. HIV is now a common infection at the Infectious Disease Clinic, Mulago. The spectrum of joint diseases seen depend on a number of factors such as, the CD4 count, HLA status and current therapy. This study included HIV patients from a heterogeneous population and was designed to determine the prevalence and clinical pattern of rheumatic manifestations among these HIV patients. Four hundred eighty seven patients were screened and 300 HIV positive patients were consecutively recruited into the study, evaluated for rheumatic manifestations and their clinical and laboratory findings documented. The prevalence of rheumatic manifestations was 27% (81 of 300). Arthralgias in 19.3% of the study population were commonest finding followed by HIV associated arthritis at 4.3%. The lower limbs were the most commonly affected with the knees (28.8%) and ankles (26.9%) contributing the highest. All patients had a negative anti-nuclear antibody test, with only two having a positive rheumatoid factor test. An association of antituberculosis drugs with joint disease was further highlighted in this study (OR 3.79 95% CI, 1.44 - 9.93). Septic arthritis due to Staphylococcus aureus was rarely observed except when the patients' level of CD4 + T cells dropped below 200 cells mm(3). The mean CD4+ count was 171 cells mm(3). Rheumatic manifestations should be considered among HIV positive adults. Arthralgias are common especially in patients using pyrazinamide.
Little, Sherard G
Between January, 2009 and December, 2013, 84 patients were identified who underwent isolated mitral valve surgery in Jamaica at The University Hospital of the West Indies and The Bustamante Hospital for Children. The most common pathology requiring surgery was rheumatic heart disease, accounting for 84% of the procedures performed. The majority of patients had regurgitation of the mitral valve (67%), stenosis of the mitral valve (22%), and mixed mitral valve disease (11%). The most common procedure performed was replacement of the mitral valve (69%), followed by mitral valve repair (29%). Among the patients, one underwent closed mitral commissurotomy. The choice of procedure differed between age groups. In the paediatric population (<18 years of age), the majority of patients underwent repair of the mitral valve (89%). In the adult population (18 years and above), the majority of patients underwent mitral valve replacement (93%). Overall, of all the patients undergoing replacement of the mitral valve, 89% received a mechanical valve prosthesis, whereas 11% received a bioprosthetic valve prosthesis. Of the group of patients who underwent mitral valve repair for rheumatic heart disease, 19% required re-operation. The average time between initial surgery and re-operation was 1.2 years. Rheumatic fever and rheumatic heart disease remain significant public health challenges in Jamaica and other developing countries. Focus must remain on primary and secondary prevention strategies in order to limit the burden of rheumatic valvulopathies. Attention should also be directed towards improving access to surgical treatment for young adults.
Eberst-Ledoux, Julie; Tournadre, Anne; Makarawiez, Claudie; Le Quang, Catherine; Soubrier, Martin; Dubost, Jean-Jacques
To determine the forms and characteristics of rheumatic diseases whose initial presentation mimics septic arthritis. Retrospective study of 398 patients hospitalized between 1979 and 2005 for arthritis diagnosed and treated as septic. In 10 cases, initial presentation of a rheumatic disease was highly suggestive of septic arthritis, and the patient was treated as such. Three had rheumatoid arthritis, 3 spondyloarthropathies, 2 unclassified rheumatic diseases, 1 Wegener granulomatosis and 1 cytosteatonecrosis. Mean time to diagnosis of rheumatic arthritis was 6 months. There were 7 males and 3 females aged from 15 to 77 years. Six had fever, and 3 had leucocytosis. Average ESR was 68 mm/1 h, and C-reactive protein was above 100 mg/l in 6 patients. Five patients had radiological signs suggestive of septic arthritis. Joint fluid count was above 100,000 WBCs/mm(3) in 2/5. Synovial biopsy suggested septic arthritis in 5 out of 6. These cases of pseudoseptic arthritis were indistinguishable from true septic arthritis. Follow-up is required in septic arthritis with negative culture findings to exclude rheumatic disease.
Palejwala, Neal V.; Yeh, Steven; Angeles-Han, Sheila T.
Inflammatory eye diseases are an important manifestation of many pediatric rheumatologic conditions. Early screening and diagnosis are imperative as these illnesses can not only result in significant visual morbidity but also be an indicator of systemic inflammation. Time to presentation of ocular inflammation varies significantly and can range from many years prior to the onset of systemic symptoms to well after the diagnosis of the rheumatologic disorder. Due to this variability in presentation, careful monitoring by an ophthalmologist is vital to preventing ocular complications and preserving vision. Both local and systemic immunosuppressive medications have been effective in the management of ocular disease. In this review, we will focus on the known ophthalmologic manifestations of common pediatric rheumatologic diseases and discuss recent advances in therapeutic considerations for these conditions. PMID:23686303
Beneventi, Fausta; Badulli, Carla; Locatelli, Elena; Caporali, Roberto; Ramoni, Véronique; Cavagnoli, Chiara; Simonetta, Margherita; Garbin, Giulia; Tinelli, Carmine; Alpini, Claudia; Montecucco, CarloMaurizio; Martinetti, Miryam; Spinillo, Arsenio
Autoimmune rheumatic diseases in pregnancies are associated with increased adverse obstetric outcomes. We compared maternal soluble human leucocyte antigen-G (sHLA-G) blood levels in subjects with a rheumatic disease preexisting pregnancy and unaffected controls. Third-trimester blood maternal sHLA-G concentrations were significantly higher in subjects with rheumatic diseases than in controls (mean 93.1ng/ml [SD 42.1] vs 58.1ng/ml [SD 96.3], p=0.003). Cord blood sHLA-G concentrations were significantly higher in rheumatic disease than in those born to control mothers (median 41.2ng/ml [IQR: 3.3-44.0] vs 17.9ng/ml [IQR: 17.2-88.1], p=0.007). A strict positive correlation (r=0.88, p<0.001) was found between the maternal and fetal titers of ANA autoantibodies as well as between maternal and fetal sHLAG circulating levels (r=0.58 and r=0.67, respectively, for controls and cases, p<0.001). Maternal s-HLA-G blood concentrations were significantly higher in subjects with rheumatic disease DEL/DEL homozygous for a polymorphism of the 3' untranslated regulatory region of HLA-G (HLA-G 14bp) than in the corresponding healthy controls (mean values 141.5ng/ml [SD: 166] vs 54.2ng/ml [SD: 35], p=0.009). Increasing maternal and cord blood levels of s-HLA-G concentrations among pregnant subjects with rheumatic diseases compared with controls suggest that autoimmune diseases prompt a maternal and fetal immune response that favors pregnancy immune tolerance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Prabhu, Mukund A; Thajudeen, Anees; Vk, Ajit Kumar; J, Tharakan; B V, Prasad Srinivas; Namboodiri, Narayanan
Left atrial (LA) reentrant tachycardias are not uncommon in regions where rheumatic heart disease is prevalent. Some of these arrhythmias may be curable by radiofrequency ablation (RFA). However, there are limited data pertaining to this in existing literature. Three patients who had rheumatic mitral valve disease with past history of surgical-/catheter-based intervention and having no significant residual disease had symptomatic atrial flutter despite optimal medical management. An electrophysiological study confirmed an LA focal/micro-reentrant mechanism in all. There was patchy scarring of the LA, and successful RFA of these arrhythmias could be achieved. The focal nature of the scar in these patients may suggest that the rheumatic involvement of the atrium or the hemodynamic consequence of the vulvar lesion causes nonuniform insult to the atrial tissue and limited scar. At least in some patients with limited scarring, early RFA may help in the maintenance of sinus rhythm. © 2016 Wiley Periodicals, Inc.
Comparative long-term results of mitral valve repair in adults with chronic rheumatic disease and degenerative disease: is repair for "burnt-out" rheumatic disease still inferior to repair for degenerative disease in the current era?
Dillon, Jeswant; Yakub, Mohd Azhari; Kong, Pau Kiew; Ramli, Mohd Faizal; Jaffar, Norfazlina; Gaffar, Intan Fariza
Mitral valve repair is perceived to be of limited durability for advanced rheumatic disease in adults. We aim to examine the long-term outcomes of repair for rheumatic disease, identify predictors of durability, and compare with repair for degenerative disease. Rheumatic and degenerative mitral valve repairs in patients aged 40 years or more were prospectively analyzed. The primary outcomes investigated were mortality, freedom from reoperation, and valve failure. Logistic regression analysis was performed to define predictors of poor outcome. Between 1997 and 2011, 253 rheumatic and 148 degenerative mitral valves were repaired. The age of patients in both groups was similar, with a mean of 54.1 ± 8.4 years versus 55.6 ± 7.3 years (P = .49). Freedom from reoperation for rheumatic valves at 5 and 10 years was 98.4%, comparable to 95.3% (P = .12) for degenerative valves. Freedom from valve failure at 5 and 10 years was 91.4% and 81.5% for rheumatic repairs and 82.5% and 75.4% for degenerative repairs, respectively (P = .15). The presence of residual mitral regurgitation greater than 2+ before discharge was the only significant independent predictor of reoperation, whereas residual mitral regurgitation greater than 2+ and leaflet procedures were significant risk factors for valve failure. The durability of rheumatic mitral valve repair in the current era has improved and is comparable to the outstanding durability of repairs for degenerative disease, even in the adult rheumatic population. Modifications of standard repair techniques, adherence to the importance of good leaflet coaptation, and strict quality control with stringent use of intraoperative transesophageal echocardiography have all contributed to the improved long-term results. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Mohan, Chandra; Assassi, Shervin
Serological and proteomic biomarkers can help clinicians diagnose rheumatic diseases earlier and assess disease activity more accurately. These markers have been incorporated into the recently revised classification criteria of several diseases to enable early diagnosis and timely initiation of treatment. Furthermore, they also facilitate more accurate subclassification and more focused monitoring for the detection of certain disease manifestations, such as lung and renal involvement. These biomarkers can also make the assessment of disease activity and treatment response more reliable. Simultaneously, several new serological and proteomic biomarkers have become available in the routine clinical setting--for example, a protein biomarker panel for rheumatoid arthritis and a myositis antibody panel for dermatomyositis and polymyositis. This review will focus on commercially available antibody and proteomic biomarkers in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis and polymyositis, and axial spondyloarthritis (including ankylosing spondylitis). It will discuss how these markers can facilitate early diagnosis as well as more accurate subclassification and assessment of disease activity in the clinical setting. The ultimate goal of current and future biomarkers in rheumatic diseases is to enable early detection of these diseases and their clinical manifestations, and to provide effective monitoring and treatment regimens that are tailored to each patient's needs and prognosis. © BMJ Publishing Group Ltd 2015.
Levinson, R D
Ocular inflammatory disease comprises of a diverse group of clinical entities that may result from autoimmune processes, infections, or both. While many individual ocular inflammatory diseases are quite rare, ocular inflammation is one of the more common causes of visual disability, including blindness, in the developed world. Better understanding of ocular inflammatory disease is an important step in designing more sophisticated therapies that may help prevent loss of visual function for these patients.
Gerhold, K; Becker, M O
Nailfold capillaroscopy has become an established method in adults for the evaluation of structural abnormalities of the microcirculation associated with rheumatic disease. It is a cornerstone for the diagnostic work-up of patients with Raynaud's phenomenon and the early diagnosis of systemic sclerosis. However, this non-invasive examination may also be valuable in children and adolescents with rheumatic diseases. Based on the scarce data available, this review focuses on capillaroscopic findings in healthy children and adolescents as well as in children with juvenile systemic sclerosis, juvenile dermatomyositis, juvenile idiopathic arthritis, and Raynaud's phenomenon. In addition, it outlines the potential benefits and limitations of nailfold capillaroscopy for routine care in paediatric rheumatology.
Oliver, Jacqueline E; Silman, Alan J
This article will review how epidemiological studies have advanced our knowledge of both genetic and environmental risk factors for rheumatic diseases over the past decade. The major rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, osteoarthritis, gout, and fibromyalgia, and chronic widespread pain, will be covered. Advances discussed will include how a number of large prospective studies have improved our knowledge of risk factors, including diet, obesity, hormones, and smoking. The change from small-scale association studies to genome-wide association studies using gene chips to reveal new genetic risk factors will also be reviewed. PMID:19490599
Lee, Y H; Bae, S-C
This study aimed to explore whether TYK2 polymorphisms are associated with susceptibility to autoimmune rheumatic diseases. We conducted a meta-analysis on the association between TYK2 polymorphisms and autoimmune rheumatic diseases. Twelve studies with a total of 16,335 patients and 30,065 controls were included in the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the 2 allele of the TYK2 rs2304256 (OR = 0.885, 95% CI = 0.802-0.978, p = 0.016). Furthermore, stratification by ethnicity identified a significant association between this polymorphism and rheumatic diseases in Caucasians (OR = 0.822, 95% CI = 0.706-0.889, p = 9.5 × 10(-7)), but not in Asians (OR = 1.127, 95% CI = 0.835-1.522, p = 0.434). Meta-analysis by rheumatic disease type revealed a significant association between the 2 allele of the TYK2 rs2304256 and SLE in Caucasians (OR = 0.737, 95% CI = 0.673-0.808, p < 1.0 × 10(-8)) but not in Asians (OR = 1.211, 95% CI = 0.813-1.804, p = 0.347). Meta-analysis revealed that the rs12720356 polymorphism was associated with susceptibility to rheumatic diseases in Caucasians (OR = 0.812, 95% CI = 0.661-0.997, p = 0.046) but not in Asians. Interestingly, the rs280519 polymorphism was significantly associated with susceptibility to SLE both in Caucasians and Asians. However, no associations were found between the rs12720270, rs280500, rs280523 and rs8108236 polymorphisms and susceptibility to rheumatic diseases. This meta-analysis demonstrates that the TYK2 rs2304256 and rs12720356 polymorphisms are associated with susceptibility to rheumatic diseases, rs2304256 polymorphism is associated with SLE in Caucasians, and rs280519 polymorphism is associated with SLE in Caucasians and Asians. © The Author(s) 2016.
Röhner, Eric; Matziolis, Georg; Perka, Carsten; Füchtmeier, Bernd; Gaber, Timo; Burmester, Gerd-Rüdiger; Buttgereit, Frank; Hoff, Paula
The role of human chondrocytes in the pathogenesis of cartilage degradation in rheumatic joint diseases has presently gained increasing interest. An active chondrocyte participation in local inflammation may play a role in the initiation and progression of inflammatory joint diseases and in a disruption of cartilage repair mechanisms resulting in cartilage degradation. In the present study, we hypothesized that inflammatory synovial fluid triggers human chondrocytes to actively take part in inflammatory processes in rheumatic joint diseases. Primary human chondrocytes were incubated in synovial fluids gained from patients with rheumatoid arthritis, psoriasis arthritis and reactive arthritis. The detection of vital cell numbers was determined by using Casy Cell Counter System. Apoptosis was measured by Annexin-V and 7AAD staining. Cytokine and chemokine secretion was determined by a multiplex suspension array. Detection of vital cells showed a highly significant decrease in chondrocyte numbers. Flow cytometry demonstrated a significant increase in apoptotic chondrocytes after the incubation. An active secretion of cytokines such as MCP-1 and MIF by chondrocytes was observed. The inflammatory synovial fluid microenvironment mediates apoptosis and cell death of chondrocytes. Moreover, in terms of cytokine secretion, it also induces an active participation of chondrocytes in ongoing inflammation.
Uluduz, Derya; Tavsanli, Mustafa Emir; Uygunoğlu, Uğur; Saip, Sabahattin; Kasapcopur, Ozgur; Ozge, Aynur; Temel, Gulhan Orekici
To assess the presence, prevalence and clinical characteristics of primary headaches in pediatric patients with chronic rheumatic diseases such as juvenile idiopathic arthritis (JIA) and familial Mediterranean fever (FMF), and to analyze the common pathophysiological mechanisms. In this noncontrolled, cross-sectional study, a semi-structured 53 item headache questionnaire was administered to subjects with FMF and JIA, and interviewed a total sample size of 601 patients younger than16years of age. The questionnaires were then analyzed according to the International Headache Society's diagnostic criteria. Children with FMF (n=378) and JIA (n=223) were studied. Each group was then divided into two subgroups according to whether the subjects reported headache or not. 29.5% of subjects with FMF reported having migraine, 37.6% probable migraine and 32.9% tension type headache (TTH). In JIA group 28.2% were diagnosed with migraine; 41.2% with probable migraine and 30.6% with TTH. No significant difference was found between all subjects with (n=258) and without (n=343) headache for variables such as living in a crowded family (p=0.95), being the first child in the family (p=0.63), academic achievement of the child (p=0.63), high education level (higher than high school) of the mother (p=0.52) and father (p=0.46). The presence of systemic disease was reported not to be effecting the daily life at the time of evaluation by 90.2% of the children with headache and 91.0% of the children without headache (p=0.94). 81.4% of the children reported their headaches were not aggravating with the exacerbation periods of their systemic disease. Family history of hypertension was reported higher by the subjects with headache (13.5% with headache and 4.0% without headache p=0.001). Diabetes mellitus was also reported higher (5.8% with headache; 0.5% without headache; p=0.006). Family history of headache was reported in 28.2% of the patients with headache whereas it was 17.4% of the
Ali, Tauseef; Lam, David; Bronze, Michael S.; Humphrey, Mary Beth
Osteoporosis commonly afflicts patients with inflammatory bowel disease, and many factors link the 2 states together. A literature review was conducted about the pathophysiology of osteoporosis in relation to inflammatory bowel disease. Screening guidelines for osteoporosis in general as well as those directed at patients with inflammatory bowel disease are reviewed, as are currently available treatment options. The purpose of this article is to increase physician awareness about osteopenia and osteoporosis occurring in patients with inflammatory bowel disease and to provide basic, clinically relevant information about the pathophysiology and guidelines to help them treat these patients in a cost-effective manner. PMID:19559158
Tsai, David M; Borah, Gregory L
The preoperative evaluation for any reconstructive or aesthetic procedure requires a detailed history of existing medical conditions and current home medications. The prevalence of rheumatic diseases such as rheumatoid arthritis, gout, and psoriasis is high, but the impact of these chronic illnesses on surgical outcome and the side effects of the powerful medications used for treatment are often underappreciated. In this review, the authors highlight key perioperative considerations specific to rheumatologic diseases and their associated pharmacologic therapies. In particular, the authors discuss the perioperative management of biological response-modifying agents, which have largely become the new standard of therapy for many rheumatic diseases. The literature reveals three key perioperative concerns with biological therapy for rheumatic disease: infection, wound healing delays, and disease flare. However, data on specific perioperative complications are lacking, and it remains controversial whether withholding biological therapy before surgery is of benefit. The risk of these adverse events is influenced by several factors: age, sex, class of biological agent, duration of exposure, dosage, onset and severity of disease, and type of surgical procedure. Overall, it remains best to develop an individualized plan. In younger patients with recent onset of biological therapy, it is reasonable to withhold therapy based on 3 to 5 half-lives of the specific agent. In older patients with a substantial history of rheumatic disease, the decision to discontinue therapy must be weighed and decided carefully in conjunction with the rheumatologist.
Stanley, J; Munsi, S; Sukumar, I P; Cherian, G
To our knowledge, no documented hemodynamic studies in larger series of young patients undergoing valve replacement for rheumatic valvular disease have been reported previously. It seems to us that the natural history of rheumatic heart disease in India often follows a rapid and fulminant course which makes an aggressive surgical approach mandatory. An operative mortality of 22 % was seen in this series. Pronounced cardiac disability together with the poor general condition and the low nutritional status contributed in no small measure to this figure. Patients have been followed for periods ranging from 6 months to 6 years following corrective surgery. A remarkable absence of thrombo-embolic phenomena was a striking feature in the follow-up. There has been no evidence of rheumatic reactivation in any of these patients. This communication reinforces the beneficial results of valve replacement even at this young age when severe mitral incompetence exists refractory to medical treatment.
Del Río Nájera, Danyella; Santana, Natalia; Peláez-Ballestas, Ingris; González-Chávez, Susana A; Quiñonez-Flores, Celia M; Pacheco-Tena, César
This study aimed to determine the prevalence of musculoskeletal (MSK) pain and rheumatic diseases in the Raramuri population (also known as Tarahumaras) who are an indigenous group in the northern state of Chihuahua in Mexico. We used the Community-Oriented Program for Control of Rheumatic Diseases (COPCORD) methodology. An analytical cross-sectional study was conducted including indigenous Raramuri aged ≥18 years from communities settled in Chihuahua City. Subjects with positive MSK pain were evaluated by primary care physicians and rheumatologists. Demographic and occupational factors such as gender and job type associated with rheumatic disease were investigated. A total of 380 indigenous Raramuri (mean age 33.6 ± 13.1 years; 37.9 % male) were interviewed. Seventy-six individuals (20 %) reported MSK pain in the last 7 days. Pain intensity was reported as "severe" and "the most severe" in 30 % of the cases. Fifty-six individuals (14.7 %) reported pain in the past and 86 (22.6 %) had either past or current pain. The prevalence of rheumatic diseases was 10.5 %. Diagnosed diseases were osteoarthritis (6.6 %), low back pain (1.6 %), spondyloarthritis (0.8 %), rheumatoid arthritis (0.5 %), non-specific arthritis (0.5 %), rheumatic regional pain syndromes (0.3 %), and fibromyalgia (0.3 %). Rheumatic disease was associated with the following variables: age (odds ratio (OR) 1.04, 95 % confidence interval (CI) 1.02-1.08; p = 0.006), family history of rheumatic symptoms (OR 6.9; 95 % CI 2.6-18.7; p < 0.001), and Health Assessment Questionnaire-Disability Index (OR 28.9; 95 % CI 2.8-289.7; p < 0.001). A high prevalence of non-traumatic MSK pain suggests the need for a rheumatic disease prevention program in the Raramuri people in Chihuahua, Mexico.
Keeling, Stephanie O; Oswald, Anna E
Pregnancy is an important condition that can affect and be affected by rheumatic disease. Overall, pregnancy is viewed as a Th2-predominant state, but several Th1-related cytokines are vital to early pregnancy. In rheumatoid arthritis for example, the majority of women improve by the beginning of the second trimester, but the majority (90%) will flare in the first 3 to 4 months postpartum. In contrast, systemic lupus erythematosus has an unpredictable course in pregnancy, leaving most rheumatologists to recommend a disease-quiescent state prior to conception. Other diseases such as scleroderma are less clear because the disease less commonly presents in the childbearing period. Many immunosuppressive medications for the rheumatic diseases are contraindicated in pregnancy because of their mechanisms of action leaving only a select few "safe" medications. Significant heterogeneity between the Food and Drug Administration (FDA) category for a medication and what a rheumatologist does in clinic leads to confusion on how a patient should be treated for active rheumatic disease both peripartum and postpartum, particularly if the patient is breastfeeding. We review the general state of pregnancy and how it is affected by prototypical rheumatic diseases including rheumatoid arthritis and systemic lupus erythematosus. In addition, we present the most commonly used disease-modifying antirheumatic drugs and immunosuppressants and explain the difference between the FDA category and clinical practice among rheumatologists. Finally, we provide some general recommendations on how to manage a rheumatic disease during pregnancy including: (a) preconception planning to ensure no teratogenic medications on board, (b) early disclosure of pregnancy to all caregivers including the rheumatologist, family physician, obstetrician, and maternal-fetal medicine specialist, and (c) planning of safe medication use for acute flare-ups and disease suppression peripartum and postpartum.
Gabriel, Sherine E; Michaud, Kaleb
Epidemiology is the study of the distribution and determinants of disease in human populations. Over the past decade there has been considerable progress in our understanding of the fundamental descriptive epidemiology (levels of disease frequency: incidence and prevalence, comorbidity, mortality, trends over time, geographic distributions, and clinical characteristics) of the rheumatic diseases. This progress is reviewed for the following major rheumatic diseases: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriatic arthritis, osteoarthritis, systemic lupus erythematosus, giant cell arteritis, polymyalgia rheumatica, gout, Sjögren's syndrome, and ankylosing spondylitis. These findings demonstrate the dynamic nature of the incidence and prevalence of these conditions--a reflection of the impact of genetic and environmental factors. The past decade has also brought new insights regarding the comorbidity associated with rheumatic diseases. Strong evidence now shows that persons with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbidity compared with the general population. Taken together, these findings underscore the complexity of the rheumatic diseases and highlight the key role of epidemiological research in understanding these intriguing conditions.
Shaw, Anita T.; Gravallese, Ellen M.
Remodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are tightly coupled and regulated to ensure the proper balance, such that there is no net change in bone mass. However, inflammation perturbs normal bone homeostasis. The impact of inflammation on bone is dependent upon the anatomic site affected, cell types, factors and cytokines present in the local microenvironment, and local mechanical forces. Cytokines are central to the pathogenesis of inflammation-induced bone loss and contribute to the uncoupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation, thereby disrupting normal remodeling. In this review, we will discuss the effects of cytokines on bone in two settings, rheumatoid arthritis (RA) and spondyloarthritis (SpA), a disease category that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, inflammatory bowel disease, and juvenile onset spondyloarthropathy. The outcome for bone in these disease settings is quite different, and an understanding of the pathogenic mechanisms leading to the net impact on bone has been essential in developing new therapeutic approaches to bone health in these diseases. PMID:26481971
Gladkova, Natalia D.; Karachistov, Alexander B.; Komarova, Lia G.; Alekseeva, Olga P.; Grunina, Elena A.
We have estimated the clinical effectiveness of several regimes and ways of low power laser therapy (LT) on the basis of a double 'blind', placebo-controlling randomizing comparative test in 454 patients with rheumatic diseases (RD). LT for RD has a well-expressed placebo effect. The level of clinical effect of LT for RD is not so high. We couldn't achieve 'a considerable improvement' in any cases, 'an improvement' was secured in only 18 percent. LT should be viewed as a symptomatic means, with a primary anesthetic and feebly expressed anti-inflammatory effect, which can not influence the course of the rheumatoid process. Only in 15 percent of patients with RD, a sufficient functioning of hemo-salivary barrier was observed, the latter providing a reserve for adaption mechanism, which leads under the influence of stressor agents of medium strength not only to anesthetic, but also to moderately expressed anti- inflammatory effect.
Duzova, Ali; Bakkaloglu, Aysin
Central nervous system (CNS) manifestations are not rare in pediatric rheumatic diseases. They may be a relatively common feature of the disease, as in systemic lupus erythematosus (SLE) and Behçet's disease. Direct CNS involvement of a systemic rheumatic disease, primary CNS vasculitis, indirect involvement secondary to hypertension, hypoxia and metabolic changes, and drug associated adverse events may all result in CNS involvement. We have reviewed the CNS manifestations of SLE, Behçet's disease, Henoch-Schönlein purpura, polyarteritis nodosa, juvenile idiopathic arthritis, juvenile ankylosing spondylitis, familial Mediterranean fever, scleroderma, sarcoidosis, Wegener's granulomatosis, Takayasu's arteritis, CINCA syndrome, Kawasaki disease, and primary CNS vasculitis; and adverse CNS effects of anti-rheumatic drugs in pediatric patients. The manifestations are diverse; ranging from headache, seizures, chorea, changes in personality, depression, memory and concentration problems, cognitive impairment, cerebrovascular accidents to coma, and death. The value of cerebrospinal fluid (CSF) examination (pleocytosis, high level of protein), auto-antibodies in serum and CSF, electroencephalography, neuroimaging with computerized tomography, magnetic resonance imaging, SPECT, PET, and angiography depends on the disease. Brain biopsy is gold standard for the diagnosis of CNS vasculitis, however it may be inconclusive in 25% of cases. A thorough knowledge of the rheumatic diseases and therapy-related adverse events is mandatory for the management of a patient with rheumatic disease and CNS involvement. Severe CNS involvement is associated with poor prognosis, and high mortality rate. High dose steroid and cyclophosphamide (oral or intravenous) are first choice drugs in the treatment; plasmapheresis, IVIG, thalidomide, and intratechal treatment may be valuable in treatment-resistant, and serious cases.
Bellan, Mattia; Boggio, Enrico; Sola, Daniele; Gibbin, Antonello; Gualerzi, Alessandro; Favretto, Serena; Guaschino, Giulia; Bonometti, Ramona; Pedrazzoli, Roberta; Pirisi, Mario; Sainaghi, Pier Paolo
The association between cancer and immune-mediated rheumatic conditions is controversial, especially as far as polymyalgia rheumatica (PMR) is concerned. Furthermore, no clinical feature has been shown to be suggestive of a paraneoplastic rheumatic syndrome. With the present study, we aim to address both these issues. The study population comprised N = 1750 patients, including N = 100 with PMR, who attended our tertiary immuno-rheumatology clinic between January 1, 2005 and November 30, 2012. A rheumatic disease was deemed paraneoplastic if cancer had been diagnosed in the 2 years preceding or following its onset. The probability of a significant association between a specific rheumatic disease and cancer was evaluated by computing the odds ratio (OR): N = 702 patients with osteoarthritis serving as controls. Furthermore, clinical features distinguishing paraneoplastic rheumatic diseases were searched for by univariate and multivariate analysis. Sjogren's syndrome (SS) [OR 3.6 (CI 95% 1.7-7.5)], PMR (OR 5.1 CI 95% 2.9-8.9), dermatomyositis/polymyositis [OR 12.09 (CI 95% 2.6-55.8)] and vasculitis [OR 3.70 (CI 95% 1.81-7.52)] are associated with cancer. At multivariate analysis, older age is associated with cancer among SS patients (p = 0.03), while in the PMR group, older age, male gender, and ≥6 tender joints are independent predictors of paraneoplastic PMR (p < 0.0004). Cancer frequently either heralds or follows rheumatic manifestations, including PMR. Older age, male gender and a more extensive joint involvement should be considered red flags for paraneoplastic PMR.
Jung, Hyun-Ju; Kim, Tae-Jong; Kim, Hyoung-Sang; Cho, Young-Nan; Jin, Hye-Mi; Kim, Moon-Ju; Kang, Jeong-Hwa; Park, Ki-Jeong; Lee, Sung-Ji; Lee, Shin-Seok; Kwon, Yong-Soo; Yoo, Dae-Hyun; Kee, Seung-Jung; Park, Yong-Wook
Triggers of indeterminate results from interferon-gamma release assays (IGRA) in patients with rheumatic diseases are still elusive. The aim of the present study was to describe predictors of indeterminate results from IGRA in the field of rheumatology. This cross-sectional study was retrospectively performed by using a database of patients with a request for QuantiFERON-TB Gold-In Tube test (QFT-GIT) for screening of latent tuberculosis infection. The study cohort included 631 patients with rheumatic diseases. All variables influencing indeterminate QFT-GIT results were investigated by logistic regression analysis. The overall frequency of indeterminate IGRA results was 6.8 % (43/631). Those with indeterminate results were more likely to be aged ≥70 years, female, visitors in winter, suffering from systemic lupus erythematosus (SLE), and using sulfasalazine or a tumor necrosis factor (TNF)-α inhibitor. In addition, a longer incubation time of >6 h increased the odds ratio of indeterminate IGRA results. In contrast, the automated ELISA processor, ankylosing spondylitis, and the use of a non-steroidal anti-inflammatory drug decreased the likelihood of indeterminate IGRA results. Lymphopenia, thrombocytopenia, anemia, and hypoalbuminemia were significantly associated with indeterminate IGRA results. Multivariate analysis revealed that SLE, use of sulfasalazine or a TNF-α inhibitor, and a manual ELISA system were significantly independent predictors of indeterminate IGRA results. The proportion of indeterminate results in patients with rheumatic diseases is not infrequent. Careful attention to the pre-analytical conditions should minimize the indeterminate results. Automation of the ELISA process seems to be a promising solution to decrease the rate of indeterminate response.
Vollmann, Manja; Pukrop, Jörg; Salewski, Christel
A rheumatic disease can severely impair a person's quality of life. The degree of impairment, however, is not closely related to objective indicators of disease severity. This study investigated the influence and the interplay of core psychological factors, i.e., personality and coping, on life satisfaction in patients with rheumatic diseases. Particularly, it was tested whether coping mediates the effects of personality on life satisfaction. In a cross-sectional design, 158 patients diagnosed with a rheumatic disease completed questionnaires assessing the Big 5 personality traits (BFI-10), several disease-related coping strategies (EFK) and life satisfaction (HSWBS). Data were analyzed using a complex multiple mediation analysis with the Big 5 personality traits as predictors, coping strategies as mediators and life satisfaction as outcome. All personality traits and seven of the nine coping strategies were associated with life satisfaction (rs > |0.16|, ps ≤ 0.05). The mediation analysis revealed that personality traits had no direct, but rather indirect effects on life satisfaction through coping. Neuroticism had a negative indirect effect on life satisfaction through less active problem solving and more depressive coping (indirect effects > -0.03, ps < 0.05). Extraversion, agreeableness, and conscientiousness had positive indirect effects on life satisfaction through more active problem solving, less depressive coping and/or a more active search for social support (indirect effects > 0.06, ps < 0.05). Personality and coping play a role in adjustment to rheumatic diseases. The interplay of these variables should be considered in psychological interventions for patients with rheumatic diseases.
Pobrotyn, Piotr; Susło, Robert; Witczak, Izabela; Milczanowski, Piotr; Drobnik, Jarosław
Rheumatic diseases are becoming more and more common in Poland with the ageing of the population. Nearly 18% of the total hospital admissions in Poland result from rheumatic diseases, which was equivalent to 350 thousand cases in the year 2008. These diseases tend to last for many decades, decreasing both the quality of life and income of the patients as well as increasing the medical institutions' workload and society's financial burden. The aim of the study was to determine whether the medical care parameters in a rheumatic disease hospital ward show any significant differences among different patient age groups - especially such that would support taking them into account as a basis for adjusting the financial coverage level of medical services. Data on hospitalizations at the Rheumatic Diseases Ward of Wroclaw University Hospital in Wroclaw in the years 2009-2015 were analyzed, taking into account the age groups, number of hospital admissions, their duration and causes. Relevant statistical data analysis was performed. The study revealed that the number of old patients hospitalized at the rheumatic diseases ward increased over the last 6 years and that such statistically significant differences do exist: on average the old patients not only tend to stay much longer at the hospital, but also suffer from a different and more diverse spectrum of diseases in comparison to their younger counterparts. The detected differences in medical care parameters support the need for more individualized medical care and increased cost of the hospital stay in the case of older patients. Consequently, those factors justify the necessity to increase the value of medical services in the case of old patients, possibly also taking into account the variation between age subgroups.
Maugeri, Norma; Rovere-Querini, Patrizia; Manfredi, Angelo A.
A network of cellular interactions that involve blood leukocytes and platelets maintains vessel homeostasis. It plays a critical role in the response to invading microbes by recruiting intravascular immunity and through the generation of neutrophil extracellular traps (NETs) and immunothrombosis. Moreover, it enables immune cells to respond to remote chemoattractants by crossing the endothelial barrier and reaching sites of infection. Once the network operating under physiological conditions is disrupted, the reciprocal activation of cells in the blood and the vessel walls determines the vascular remodeling via inflammatory signals delivered to stem/progenitor cells. A deregulated leukocyte/mural cell interaction is an early critical event in the natural history of systemic inflammation. Despite intense efforts, the signals that initiate and sustain the immune-mediated vessel injury, or those that enforce the often-prolonged phases of clinical quiescence in patients with vasculitis, have only been partially elucidated. Here, we discuss recent evidence that implicates the prototypic damage-associated molecular pattern/alarmin, the high mobility group box 1 (HMGB1) protein in systemic vasculitis and in the vascular inflammation associated with systemic sclerosis. HMGB1 could represent a player in the pathogenesis of rheumatic diseases and an attractive target for molecular interventions. PMID:27242789
While arachidonic acid (AA), which is classified into n-6 polyunsaturated fatty acid (PUFA), has been mainly recognized as a substrate of pro-inflammatory mediators, eicosapentaenoic acid or docosahexaenoic acid, which are classified into n-3 PUFA, is currently identified as substrates of mediators inducing resolution of inflammation, namely pro-resolving mediators (SPM). As with any other pathological conditions, it is gradually elucidated that SPMs contributes a certain effect on joint inflammation. In osteoarthritis (OA), Lipid fractions extracted from adipocytes, especially in infrapatellar fat pad rather than subcutaneous tissue induce T cell skewing for producing IFN-γ or decrease the production of IL-12p40 from macrophages. In synovial tissues form OA, there are some of known receptors for SPM. In the synovial fluid from rheumatoid arthritis (RA), it could be identified and quantified a certain kind of SPMs such as maresin 1, lipoxin A4 and resolvin D5. In murine models of arthritis, some of SPMs are found to have some functions to reduce tissue damage. Correctively, SPMs might have some potential to a novel therapeutic target for arthritis or any other rheumatic diseases.
Hoes, J N; Jacobs, J W G; Boers, M; Boumpas, D; Buttgereit, F; Caeyers, N; Choy, E H; Cutolo, M; Da Silva, J A P; Esselens, G; Guillevin, L; Hafstrom, I; Kirwan, J R; Rovensky, J; Russell, A; Saag, K G; Svensson, B; Westhovens, R; Zeidler, H; Bijlsma, J W J
Objective To develop evidence‐based recommendations for the management of systemic glucocorticoid (GC) therapy in rheumatic diseases. Methods The multidisciplinary guideline development group from 11 European countries, Canada and the USA consisted of 15 rheumatologists, 1 internist, 1 rheumatologist–epidemiologist, 1 health professional, 1 patient and 1 research fellow. The Delphi method was used to agree on 10 key propositions related to the safe use of GCs. A systematic literature search of PUBMED, EMBASE, CINAHL, and Cochrane Library was then used to identify the best available research evidence to support each of the 10 propositions. The strength of recommendation was given according to research evidence, clinical expertise and perceived patient preference. Results The 10 propositions were generated through three Delphi rounds and included patient education, risk factors, adverse effects, concomitant therapy (ie, non‐steroidal anti‐inflammatory drugs, gastroprotection and cyclo‐oxygenase‐2 selective inhibitors, calcium and vitamin D, bisphosphonates) and special safety advice (ie, adrenal insufficiency, pregnancy, growth impairment). Conclusion Ten key recommendations for the management of systemic GC‐therapy were formulated using a combination of systematically retrieved research evidence and expert consensus. There are areas of importance that have little evidence (ie, dosing and tapering strategies, timing, risk factors and monitoring for adverse effects, perioperative GC‐replacement) and need further research; therefore also a research agenda was composed. PMID:17660219
Alijotas-Reig, Jaume; Esteve-Valverde, Enrique; Ferrer-Oliveras, Raquel
Rheumatic and systemic autoimmune diseases occur in women and, to a lesser degree, men of reproductive age. These disorders have to be clinically nonactive before conception, which is usually only possible after anti-inflammatory and immunosuppressive treatment. We must be alert since 50% of pregnancies are unplanned. Physicians should know the embryo-foetal toxicity of these drugs during pregnancy and lactation. This January 2016-updated review allows us to conclude that the majority of immunosuppressives available -anti-TNF inhibitors included- can be used before and during pregnancy, with the exception of cyclophosphamide, methotrexate, mycophenolate and leflunomide. Lactation is permitted with all drugs except methotrexate, leflunomide, mycophenolate and cyclophosphamide. Although data on abatacept, belimumab, rituximab, tocilizumab and anakinra are scant, preliminary reports agree on their safety during pregnancy and, probably, lactation. Cyclophosphamide and sulfasalazine apart, no negative effects on sperm quality, or embryo-foetal anomalies in men treated with immunosuppressives have been described. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Beaton, Andrea; Sable, Craig
Rheumatic heart disease (RHD) key opinion leaders, health ministers, clinicians, and industry representatives gathered in Ethiopia in February 2015. The question: how to eradicate RHD in Africa. The response: the Addis Ababa communiqué, a practical document outlining seven major barriers to RHD control in Africa and seven strategies to address them.
Sun, Gavin; Hazlewood, Glen; Kaplan, Gilaad G.; Eksteen, Bertus
Objective. Environmental risk factors, such as air pollution, have been studied in relation to the risk of development of rheumatic diseases. We performed a systematic literature review to summarize the existing knowledge. Methods. MEDLINE (1946 to September 2016) and EMBASE (1980 to 2016, week 37) databases were searched using MeSH terms and keywords to identify cohort, case-control, and case cross-over studies reporting risk estimates for the development of select rheumatic diseases in relation to exposure of measured air pollutants (n = 8). We extracted information on the population sample and study period, method of case and exposure determination, and the estimate of association. Results. There was no consistent evidence of an increased risk for the development of rheumatoid arthritis (RA) with exposure to NO2, SO2, PM2.5, or PM10. Case-control studies in systemic autoimmune rheumatic diseases (SARDs) indicated higher odds of diagnosis with increasing PM2.5 exposure, as well as an increased relative risk for juvenile idiopathic arthritis (JIA) in American children <5.5 years of age. There was no association with SARDs and NO2 exposure. Conclusion. There is evidence for a possible association between air pollutant exposures and the development of SARDs and JIA, but relationships with other rheumatic diseases are less clear. PMID:27847517
Pers, Yves-Marie; Jorgensen, Christian
A number of microRNAs have been implicated in the pathogenesis of various rheumatic diseases, and evidence in support of the therapeutic potential of microRNA-based strategies for these conditions is growing, as demonstrated by several new findings published in 2012.
Xynos, Ioannis D.; Tektonidou, Maria G.; Pikazis, Dimitrios
We report 2 cases of leishmaniasis in patients with autoimmune rheumatic diseases in Greece. To assess trends in leishmaniasis reporting in this patient population, we searched the literature for similar reports from Europe. Reports increased during 2004–2008, especially for patients treated with anti–tumor necrosis factor agents. PMID:19523302
Wu, Wei; Chen, Qiang; Zhang, Liangcheng; Chen, Wenhua
Pregnancy increases stress on the circulation of parturient with mitral stenosis secondary to rheumatic heart disease and increases the risk of peripartum heart failure, especially during delivery. This study investigated the epidural anesthesia management for cesarean section in pregnant women with rheumatic heart disease and mitral stenosis. 48 parturients with rheumatic heart disease and mitral stenosis that had cesarean section deliveries with epidural anesthesia in the Union Hospital, Fujian Medical University (Fuzhou, China) from Jan 2002 to Dec 2012 were retrospectively analyzed. Heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), central venous pressure (CVP), fluid intake volume and fluid output volume (blood loss + urine volume) were analyzed. Medication included digitalis drugs for heart failure or potential heart failure, digoxin and furosemide for chronic congestive heart failure and beta blockers for arrhythmia. Frequent premature ventricular contractions were treated with lidocaine and propafenone. Dexamethasone was administered when heart failure occurred during less than 37 weeks gestation. HR, SAP, DAP, MAP and CVP were significantly increased at the time of delivery. The fluid intake volume was more elevated in the NYHA III-IV group of parturients than the NYHA I-II group, while fluid output volume was less. All parturients survived. Epidural anesthesia was applied successfully for cesarean sections for parturients with rheumatic heart disease and mitral stenosis.
Widdifield, Jessica; Bernatsky, Sasha; Thorne, J Carter; Bombardier, Claire; Jaakkimainen, R Liisa; Wing, Laura; Paterson, J Michael; Ivers, Noah; Butt, Debra; Lyddiatt, Anne; Hofstetter, Catherine; Ahluwalia, Vandana; Tu, Karen
The Wait Time Alliance recently established wait time benchmarks for rheumatology consultations in Canada. Our aim was to quantify wait times to primary and rheumatology care for patients with rheumatic diseases. We identified patients from primary care practices in the Electronic Medical Record Administrative data Linked Database who had referrals to Ontario rheumatologists over the period 2000-2013. To assess the full care pathway, we identified dates of symptom onset, presentation in primary care and referral from electronic medical records. Dates of rheumatologist consultations were obtained by linking with physician service claims. We determined the duration of each phase of the care pathway (symptom onset to primary care encounter, primary care encounter to referral, and referral to rheumatologist consultation) and compared them with established benchmarks. Among 2430 referrals from 168 family physicians, 2015 patients (82.9%) were seen by 146 rheumatologists within 1 year of referral. Of the 2430 referrals, 2417 (99.5%) occurred between 2005 and 2013. The main reasons for referral were osteoarthritis (32.4%) and systemic inflammatory rheumatic diseases (30.6%). Wait times varied by diagnosis and geographic region. Overall, the median wait time from referral to rheumatologist consultation was 74 (interquartile range 27-101) days; it was 66 (interquartile range 18-84) days for systemic inflammatory rheumatic diseases. Wait time benchmarks were not achieved, even for the most urgent types of referral. For systemic inflammatory rheumatic diseases, most of the delays occurred before referral. Rheumatology wait times exceeded established benchmarks. Targeted efforts are needed to promote more timely access to both primary and rheumatology care. Routine linkage of electronic medical records with administrative data may help fill important gaps in knowledge about waits to primary and specialty care.
Widdifield, Jessica; Bernatsky, Sasha; Thorne, J. Carter; Bombardier, Claire; Jaakkimainen, R. Liisa; Wing, Laura; Paterson, J. Michael; Ivers, Noah; Butt, Debra; Lyddiatt, Anne; Hofstetter, Catherine; Ahluwalia, Vandana; Tu, Karen
Background: The Wait Time Alliance recently established wait time benchmarks for rheumatology consultations in Canada. Our aim was to quantify wait times to primary and rheumatology care for patients with rheumatic diseases. Methods: We identified patients from primary care practices in the Electronic Medical Record Administrative data Linked Database who had referrals to Ontario rheumatologists over the period 2000-2013. To assess the full care pathway, we identified dates of symptom onset, presentation in primary care and referral from electronic medical records. Dates of rheumatologist consultations were obtained by linking with physician service claims. We determined the duration of each phase of the care pathway (symptom onset to primary care encounter, primary care encounter to referral, and referral to rheumatologist consultation) and compared them with established benchmarks. Results: Among 2430 referrals from 168 family physicians, 2015 patients (82.9%) were seen by 146 rheumatologists within 1 year of referral. Of the 2430 referrals, 2417 (99.5%) occurred between 2005 and 2013. The main reasons for referral were osteoarthritis (32.4%) and systemic inflammatory rheumatic diseases (30.6%). Wait times varied by diagnosis and geographic region. Overall, the median wait time from referral to rheumatologist consultation was 74 (interquartile range 27-101) days; it was 66 (interquartile range 18-84) days for systemic inflammatory rheumatic diseases. Wait time benchmarks were not achieved, even for the most urgent types of referral. For systemic inflammatory rheumatic diseases, most of the delays occurred before referral. Interpretation: Rheumatology wait times exceeded established benchmarks. Targeted efforts are needed to promote more timely access to both primary and rheumatology care. Routine linkage of electronic medical records with administrative data may help fill important gaps in knowledge about waits to primary and specialty care. PMID:27398365
Halsted R. Holman, in a 1994 Arthritis & Rheumatism editorial, discusses how "thought barriers" can make our understanding of rheumatic diseases more difficult. The medical teaching-practice has traditionally been centered on acute disease; however, most rheumatic diseases are chronic. There is also the prevailing notion of a single lesion for each disease, a concept stemming from infectious diseases. Related to this is an investigative strategy of reductionism. We commonly overlook interactive biological pathways, which make up many of our diseases. In this regard, Holman advises us that 1. abnormalities are not necessarily harmful; 2. in rheumatological diseases, not only are multivariate causes-pathways operative, but the same pathways can be influenced by separate influences; 3. in chronic disease, "the task of the physician is to manage the course of disease over time," a scheme where the patient is at the center of achieving and monitoring progress; and 4. our current medical care system is mainly based on acute care, and needs to be adopted more to the needs of chronic care. In the current manuscript, three additional "thought barriers" are proposed: 1. our urge to lump diseases is too simplistic and hinders progress; 2. the same is true for our resistance in not including diseased control groups in genetic association studies; and 3. misuse of the controlled clinical trial. The popular inductive reasoning with the propensity to prove rather than to falsify one's self might be the common denominator in many of the barriers discussed.
This Memorandum summarizes the report of a meeting held in Geneva on 7-9 September 1994. Experts and representatives from different countries and regions, as well as WHO, the International Society and Federation of Cardiology, UNESCO, and the International Council of Nurses evaluated the experience in controlling rheumatic fever/rheumatic heart disease (RF/RHD) and provided an update on the essential components of RF/RHD prevention, including new areas for research in primary prevention. The meeting's recommendations should be applicable in all countries where RF/RHD is a health problem. PMID:8846483
Purpose of review Kinases inhibitors are now used for the treatment of autoimmune diseases. Here are reviewed the most recent findings related to their mechanism of action and some of the newest molecules and targets which are being investigated for autoimmune and inflammatory disorders. Recent findings Similarly to p38 inhibitors, Syk inhibitors have not fulfilled the expectations of researchers and clinicians and will likely not be used therapeutically in autoimmunity. BTK inhibitors remain in the preclinical phase. Studies on the mechanism of action of successful Jak inhibitors have revealed that besides T and B cells, bone cells such as osteoclasts and innate immunity cells such as dendritic cells are positively affected. More specific, novel Jak inhibitors are now in clinical trials and newer Jak inhibitors are being developed. Other kinases are emerging from basic studies as potentially druggable and will surely be investigated. Summary First generation pan-Jak inhibitors can be useful for a wide variety of pathologies. They act on innate immune cells and can promote tolerance. More specific inhibitors will soon be available and these may be used in a disease-specific manner. PMID:24419749
McGlacken-Byrne, S M; Parry, H M; Currie, P F; Wilson, N J
Our patient is an 18-year-old Caucasian woman from the UK who developed severe mitral stenosis on a history of childhood acute rheumatic fever (ARF) and rheumatic heart disease (RHD). She had been reporting of her oral penicillin secondary prophylaxis regimen since diagnosis. At the age of 15 years, a new murmur was discovered during routine cardiac follow-up. An echocardiogram confirmed moderate-severe mitral stenosis. One year later, her exercise tolerance significantly deteriorated and she subsequently underwent balloon valvuloplasty of her mitral valve to good effect. Our case emphasises the evidence base supporting the use of monthly intramuscular penicillin injection to prevent ARF recurrence and RHD progression; it also emphasises the reduced efficacy of oral penicillin prophylaxis in this context. It particularly resonates with regions of low rheumatic fever endemicity. The long-term cardiac sequelae of ARF can be devastating; prescribing the most effective secondary prophylaxis regimen is essential.
Janssen, M; Dijkmans, B A; van der Sluys, F A; van der Wielen, J G; Havenga, K; Vandenbroucke, J P; Lamers, C B; Zwinderman, A H; Cats, A
The aim of this study was to compare the frequency of upper gastrointestinal (GI) complaints and complications between chronic rheumatic patients who are most often non-steroidal anti-inflammatory drugs (NSAIDs) users and patients with other chronic conditions. In this comparison we took into account known risk factors for upper GI disease. To achieve the study aims we performed a combined cross-sectional and retrospective study. We therefore interviewed by means of a standard questionnaire, an index and a reference group, about current upper GI complaints and previous complications. The former group comprises 578 outpatients of the Department of Rheumatology, the latter of 531 outpatients of the Departments of Internal Medicine, Pulmonology, and Cardiology. Although the number of patients in the index group being chronically treated with NSAIDs was very high (62% versus 9% in the reference group: P < 0.00001), no between-group differences were found for the frequency of several current upper gastrointestinal complaints or for the number of upper gastrointestinal investigations ever performed (35% and 37%: NS) or for the use of gastric drugs (14% and 10%: NS). Risk factors for upper GI complaints were not related to NSAID use but with the use of prednisolone, history of duodenal ulcer disease, family history of peptic ulcer disease and female sex. For peptic ulcer disease, bleeding, and gastric surgery, the only difference between the index and reference groups concerned the frequency of gastric ulcers (6.7% and 2.8%: P < 0.005), which was highest in patients with rheumatoid arthritis. Upper GI bleeding had more often been present in male seropositive rheumatoid arthritis patients (13.2% [corrected] and 4.5%: P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Goodman, Anna; Kajantie, Eero; Osmond, Clive; Eriksson, Johan; Koupil, Ilona; Thornburg, Kent; Phillips, David I W
One previous, preliminary study reported that the length of the umbilical cord at birth is related to the risk of developing chronic rheumatic heart disease in later life. We sought to replicate this finding. Prospective, population-based birth cohort. We traced 11,580 individuals born between 1915 and 1929 in Uppsala, Sweden. We identified cases with a main or secondary diagnosis of chronic rheumatic heart disease in the Swedish national inpatient, outpatient or death registers. Archived obstetric records provided data on umbilical cord length, gestational age, birthweight and placental weight. There were 136 patients with chronic rheumatic heart disease (72 men and 64 women) with a mean age at first hospital admission of 68 years (range 36-92). There was evidence of a positive association between umbilical cord length and risk of subsequent chronic rheumatic heart disease. The overall hazard ratio in the Swedish study (1.13, 95% confidence interval 1.01 to 1.27) was similar to that of the previous study, with some suggestion of larger effect in men than in women. No other birth characteristics were predictive except for weak evidence of a protective effect of higher birthweight in men. People with longer umbilical cords at birth are more likely to develop chronic rheumatic heart disease in later life. As longer umbilical cords have more spiral arteries and a higher vascular resistance, we hypothesize that the increased pressure load on the heart leads to changes in endothelial biology and increased vulnerability to the autoimmune process initiated by infection with β-haemolytic streptococci. © The European Society of Cardiology 2014.
Reveille, J D
The revolution in microbiology and genetics that has transpired in the past few years has brought fresh debate in the question of the relative contributions of nature and nurture in susceptibility to the rheumatic diseases. For nature, a variety of immunologically relevant genes have been identified whose presence has been shown to be associated either with an increased risk for certain diseases or for complications or subsets thereof. For nurture, the role of infectious agents in disease triggering and modification has been found.
Nordet, Porfirio; Lopez, Raimundo; Sarmiento, Luis; Nordet, Porfirio; Dueñas, Alfredo
Summary Background Rheumatic fever (RF) and rheumatic heart disease (RHD) are still major medical and public health problems mainly in developing countries. Pilot studies conducted during the last five decades in developed and developing countries indicated that the prevention and control of RF/RHD is possible. During the 1970s and 1980s, epidemiological studies were carried out in selected areas of Cuba in order to determine the prevalence and characteristics of RF/RHD, and to test several long-term strategies for prevention of the diseases. Methods Between 1986 and 1996 we carried out a comprehensive 10-year prevention programme in the Cuban province of Pinar del Rio and evaluated its efficacy five years later. The project included primary and secondary prevention of RF/RHD, training of personnel, health education, dissemination of information, community involvement and epidemiological surveillance. Permanent local and provincial RF/RHD registers were established at all hospitals, policlinics and family physicians in the province. Educational activities and training workshops were organised at provincial, local and health facility level. Thousands of pamphlets and hundreds of posters were distributed, and special programmes were broadcast on the public media to advertise the project. Results There was a progressive decline in the occurrence and severity of acute RF and RHD, with a marked decrease in the prevalence of RHD in school children from 2.27 patients per 1 000 children in 1986 to 0.24 per 1 000 in 1996. A marked and progressive decline was also seen in the incidence and severity of acute RF in five- to 25-year-olds, from 18.6 patients per 100 000 in 1986 to 2.5 per 100 000 in 1996. There was an even more marked reduction in recurrent attacks of RF from 6.4 to 0.4 patients per 100 000, as well as in the number and severity of patients requiring hospitalisation and surgical care. Regular compliance with secondary prophylaxis increased progressively and the
García-Doval, Ignacio; Pérez-Zafrilla, Beatriz; Descalzo, Miguel Angel; Roselló, Rosa; Hernández, Maria Victoria; Gómez-Reino, Juan J; Carmona, Loreto
To estimate the incidence of hospitalisation due to varicella zoster virus (VZV) infection in patients treated with tumour necrosis factor (TNF) antagonists for inflammatory rheumatic conditions and to compare it with the expected rate in the general population. Secondary data analysis was performed of two large databases: (1) the national registry of rheumatic diseases patients treated with biological agents (BIOBADASER); and (2) the national hospital discharge database Conjunto Mínimo Básico de Datos al Alta Hospitalaria. Hospitalisations due to shingles or chickenpox were analysed. For each condition the incidence rate (IR) and the age and gender standardised IR per 100,000 person-years plus the standardised incidence ratio (SIR) and the standardised incidence difference (SID) were estimated. In patients exposed to TNF antagonists, the estimated IR of hospitalisation due to shingles was 32 cases per 100,000 patient-years (95% CI 14 to 78), the expected rate in the general population was 3.4 (95% CI 3.2 to 3.5), the SIR was 9 (95% CI 3 to 20) and the SID was 26 (95% CI 14 to 37). The estimated IR of hospitalisation due to chickenpox was 26 cases per 100,000 (95% CI 10 to 69), the expected rate was 1.9 (95% CI 1.8 to 2.0), the SIR was 19 (95% CI 5 to 47) and the SID 33 (95% CI 21 to 45). Patients suffering rheumatic diseases exposed to TNF antagonists are hospitalised due to VZV infections significantly more frequently than expected in the general population. Since the absolute IR of hospitalisations due to chickenpox and shingles is low in these patients, the implementation of risky preventive measures may not be justified at present.
Doria, Andrea; Iaccarino, Luca; Arienti, Silvia; Ghirardello, Anna; Zampieri, Sandra; Rampudda, Maria Elisa; Cutolo, Maurizio; Tincani, Angela; Todesco, Silvano
One of the most important immunological modifications during pregnancy is the Th1/Th2 shift, due to the progressive increase of progesterone and estrogens during pregnancy, which reach their peak-level in the third trimester of gestation. At high levels, estrogens seem mainly to suppress Th1 cytokines and stimulate Th2-mediated immunological responses as well as antibody production. For this reason Th1-mediated diseases, like rheumatoid arthritis (RA), tend to improve and Th2-mediated disease, like systemic lupus erythematosus (SLE), tend to worsen during pregnancy. SLE is the autoimmune rheumatic disease in which pregnancy most frequently occurs because it predominantly affects young females in their childbearing age. Other autoimmune rheumatic diseases, including RA, are less frequently observed during pregnancy due to their low female-to-male ratio and peak onset after the age of 40. This review is focused on the disease course, gestational outcome and management of patients with SLE and RA during pregnancy.
Sfikakis, Petros P; Bournia, Vasiliki-Kalliopi; Sidiropoulos, Prodromos; Boumpas, Dimitrios T; Drosos, Alexandros A; Kitas, George D; Konstantonis, George; Liossis, Stamatis N; Manoussakis, Menelaos N; Sakkas, Lazaros; Tektonidou, Maria; Tzioufas, Athanasios G; Vlachoyiannopoulos, Panayiotis G; Kani, Chara; Paterakis, Panayiotis; Litsa, Panayiota; Vassilopoulos, Dimitrios
To directly assess the prevalence of inflammatory rheumatic disease under treatment with biologic disease modifying anti-rheumatic drugs (b-DMARDs) and compare treatment patterns between rheumatoid arthritis (RA) and spondyloarthropathy (SpA), including psoriatic arthritis. The obligatory country-wide prescription electronic database covering 10.223.000 Greek citizens (95.1% of the population, 99.5% Caucasian), all of whom with fully reinbursed access to b-DMARDs, was used to retrospectively capture all patients under b-DMARDs for RA/SpA between June 2014-May 2015. Age, gender and medications for RA/SpA and co-morbid classical cardiovascular risk factors (hypertension, dyslipidaemia, diabetes) were retrieved and analysed. A total of 9.824 RA (61.2±14.0 years, 79% women) and 9.279 SpA patients (51.4±13.1 years, 41% women) using pharmacy-dispensed prescriptions for b-DMARDs were identified (overall prevalence 0.19%). Tumour necrosis factor inhibitors were used in 73% and 99% of RA and SpA patients, respectively. B-DMARD monotherapy (RA: 18.71%, SpA: 52.11%), b-DMARD switching during 12 months (RA: 7.73%, SpA: 6.26%), and use of methotrexate (RA: 50.25%, SpA: 27.35%) and corticosteroids (RA: 55.8%, SpA: 23.63%) differed between the two patient subgroups. In both subgroups, women received more often than men methotrexate, leflunomide, hydroxychloroquine and corticosteroids, and less often b-DMARD monotherapy. After adjustments for age, gender and concomitant drugs, the probability for anti-hypertensive and lipid-lowering drug prescription was higher in SpA than RA [OR=1.41 (95%CI: 1.29-1.54) and 1.24 (1.14-1.36), respectively, p<0.001], whereas for anti-diabetics it was similar. In the first country-wide study that examines the characteristics of rheumatic disease patients under b-DMARD we show that their exact prevalence is 0.19%, with RA patients being older by 10 years, only slightly more numerous, and less likely to receive treatment for hypertension and
Niklas, Arkadiusz A.; Majewski, Dominik; Puszczewicz, Mariusz J.
The majority of rheumatic diseases belong to the group of autoimmune diseases and are associated with autoantibody production. Their etiology is not fully understood. Certain medications and environmental factors may have an influence on the occurrence of rheumatic diseases. Establishing a cause-effect relationship between a certain factor and disease induction is not always simple. It is important to administer the drug continuously or monitor exposure to a given factor in the period preceding the onset of symptoms. The lack of early diagnosed autoimmune disease, or finally the lack of symptoms within a few weeks/months after discontinuation of the drug/cessation of exposure, is also important. The most frequently mentioned rheumatic diseases caused by drugs and environmental factors include systemic lupus erythematosus (SLE), scleroderma, systemic vasculitis, polymyositis, dermatomyositis, and Sjögren’s syndrome. The objective of this study is to summarize current knowledge on rheumatic diseases induced by drugs and environmental factors. PMID:27826170
Niklas, Arkadiusz A.; Majewski, Dominik; Puszczewicz, Mariusz
The majority of rheumatic diseases belong to the group of autoimmune diseases and are associated with autoantibody production. Their etiology is not fully understood. Certain medications and environmental factors may have an influence on the occurrence of rheumatic diseases. Establishing a cause-effect relationship between a certain factor and disease induction is not always simple. It is important to administer the drug continuously or monitor exposure to a given factor in the period preceding the onset of symptoms. The lack of previously diagnosed autoimmune disease, or finally the lack of symptoms within a few weeks/months after discontinuation of the drug/cessation of exposure, is also important. The most frequently mentioned rheumatic diseases caused by drugs and environmental factors include systemic lupus erythematosus, scleroderma, systemic vasculitis, polymyositis, dermatomyositis, and Sjögren's syndrome. The objective of this study is to summarize current knowledge on rheumatic diseases induced by drugs and environmental factors. PMID:27504022
Progress in the field of pediatric rheumatolgy has been extraordinary; subspecialty is accepted as essential, vital, indispensible and distinct from adult rheumatology. It is clear that arthritis in children is more heterogeneous than RA. Although there are similarities between the inflammatory arthritides occuring in adults and children, RA and JIA appear to be distinct phenotypically with exception for the older child with RF-positive polyarticular arthritis. Progress in molecular biology has enabled us to diagnose those children earlier, and treat them more efficaciously with variety of drugs and biologic agents. In recent years a new group of hereditary autoinflammatory disorders has emerged. These rare syndromes are charaterized by recurrent episodes of seemingly unprovoked, intermittent inflammation. In the near future we will be able to distinguish various subtypes of autoimune/autoinflammatory diseases earlier in the course, have a better understanding of the biomarkers and other prognostic factors, and most importantly treat them earlier with extended set of various new exciting drugs and biological therapy.
Zühlke, Liesl; Mirabel, Mariana; Marijon, Eloi
Africa has one of the highest prevalence of heart diseases in children and young adults, including congenital heart disease (CHD) and rheumatic heart disease (RHD). We present here an extensive review of recent data from the African continent highlighting key studies and information regarding progress in CHD and RHD since 2005. Main findings include evidence that the CHD burden is underestimated mainly due to the poor outcome of African children with CHD. The interest in primary prevention for RHD has been recently re-emphasised, and new data are available regarding echocardiographic screening for subclinical RHD and initiation of secondary prevention. There is an urgent need for comprehensive service frameworks to improve access and level of care and services for patients, educational programmes to reinforce the importance of prevention and early diagnosis and a relevant research agenda focusing on the African context.
Rhee, Rennie L; Von Feldt, Joan M; Schumacher, H Ralph; Merkel, Peter A
Web-based patient education materials and printed pamphlets are frequently used by providers to inform patients about their rheumatic disease. Little attention has been given to the readability and appropriateness of patient materials. The objective of this study was to examine the readability and suitability of commonly used patient education materials for osteoarthritis (OA), rheumatoid arthritis, systemic lupus erythematosus, and vasculitis. Five or 6 popular patient resources for each disease were chosen for evaluation. Readability was measured using the Flesch-Kincaid reading grade level and suitability was determined by the Suitability Assessment of Materials (SAM), a score that considers characteristics such as content, graphics, layout/topography, and cultural appropriateness. Three different reviewers rated the SAM score and means were used in the analysis. Twenty-three resources written on the 4 diseases were evaluated. The education material for all 4 diseases studied had readability above the eighth-grade level and readability did not differ among the diseases. Only 5 of the 23 resources received superior suitability scores, and 3 of these 5 resources were written for OA. All 4 diseases received adequate suitability scores, with OA having the highest mean suitability score. Most patient education materials for rheumatic diseases are written at readability levels above the recommended sixth-grade reading level and have only adequate suitability. Developing more appropriate educational resources for patients with rheumatic diseases may improve patient comprehension. Copyright © 2013 by the American College of Rheumatology.
Thieme, H; Löffler, K; Borgetto, B
The purpose of the present study is to describe the frequency and potential determinants of occupational therapy routine services in patients with rheumatic diseases. The study is based on a secondary analysis of the RheumaDat database. The results of the survey on 907 patients were analyzed regarding frequency of occupational therapy routine services and related sociodemographic and disease-specific variables. Approximately 8% of the study population received occupational therapy, patients with rheumatoid arthritis representing the largest proportion of these at 13%. Only patients with osteoarthritis showed a clear treatment pattern. Patients from this group receiving occupational therapy were older, had a longer duration of disease and were more affected. No clear appraisal of the therapy status in the rheumatoid arthritis or fibromyalgia group could be made. The results indicate shortages and the lack of a clear system in occupational therapy routine services in patients with different rheumatic diseases.
Saxena, Anita; Desai, Ankush; Narvencar, Kedareshwar; Ramakrishnan, Sivasubramanian; Thangjam, Rajendra Singh; Kulkarni, Snehal; Jacques' E Costa, Ana Karina; Mani, Kalaivani; Dias, Amit; Sukharamwala, Ritesh
Rheumatic heart disease (RHD) continues to be major public health burden in developing world. Echocardiographic screening in school children has shown that subclinical RHD cases are several times more than clinical cases. Recent reports have used World Heart Federation (WHF) criteria. Objective of present study was to determine RHD prevalence using WHF criteria in Indian children. Children (5-15years) from randomly selected schools across four sites were included. After focused clinical evaluation, echocardiography was performed using WHF criteria in all children. Images/loops of abnormal cases were analyzed independently by an additional experienced cardiologist. Children with murmur and confirmatory echocardiography were categorized 'clinical RHD'; those with abnormal echocardiography alone were labeled 'subclinical RHD'. Among 16,294 children included, mean age was 10.8 ± 2.9years; 55.1% were males; 11,405 (70%) were from rural areas and 3978 (24.4%) were from government schools. We detected RHD by echocardiography in 125 children [prevalence: 7.7/1000 (95% CI 6.3, 9.0)]. Borderline RHD was present in 93 children (5.7/1000, 95% CI 4.6, 6.9), definite RHD in 32 (2/1000, 95% CI 1.2, 2.6), and clinical RHD in six [0.36/1000, 95% CI: 0.1-0.7]. On univariate analysis, older age, female gender, and higher waist circumference were associated while on multivariate analysis, older age (OR 1.18, 95% CI: 1.09, 1.26) and female gender (OR 1.61, 95% CI: 1.13, 2.3) were associated with RHD. RHD prevalence varies in different parts of India. Echocardiographic prevalence is several times higher than clinical and underscores importance of echocardiographic screening in community. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Burke, Rebecca J; Chang, Christopher
Acute rheumatic fever is an inflammatory sequela of Group A Streptococcal pharyngitis that affects multiple organ systems. The incidence of acute rheumatic fever has been declining even before the use of antibiotics became widespread, however the disease remains a significant cause of morbidity and mortality in children, particularly in developing countries and has been estimated to affect 19 per 100,000 children worldwide. Acute rheumatic fever is a clinical diagnosis, and therefore subject to the judgment of the clinician. Because of the variable presentation, the Jones criteria were first developed in 1944 to aid clinicians in the diagnosis of acute rheumatic fever. The Jones criteria have been modified throughout the years, most recently in 1992 to aid clinicians in the diagnosis of initial attacks of acute rheumatic fever and to minimize overdiagnosis of the disease. Diagnosis of acute rheumatic fever is based on the presence of documented preceding Group A Streptococcal infection, in addition to the presence of two major manifestations or one major and two minor manifestations of the Jones criteria. Without documentation of antecedent Group A Streptococcal infection, the diagnosis is much less likely except in a few rare scenarios. Carditis, polyarthritis and Sydenham's chorea are the most common major manifestations of acute rheumatic fever. However, despite the predominance of these major manifestations of acute rheumatic fever, there can be significant overlap with other disorders such as Lyme disease, serum sickness, drug reactions, and post-Streptococcal reactive arthritis. This overlap between disease processes has led to continued investigation of the pathophysiology as well as development of new biomarkers and laboratory studies to aid in the diagnosis of acute rheumatic fever and distinction from other disease processes.
Monson, Thomas P.; Miller, Timothy T.; Nolan, Charles M.
We studied cefotaxime in the treatment of gonococcal and nongonococcal pelvic inflammatory disease. Cefotaxime was uniformly effective against gonococcal pelvic inflammatory disease. However, 4 of 11 patients with nongonococcal pelvic inflammatory disease had a suboptimal response. PMID:6275789
Ek, Michelle; Vladic-Stjernholm, Ylva; Günther, Anders; Hällsjö-Sander, Caroline; Jacobsen, Per-Herman
Valvular heart disease constitutes the majority of all causes of heart disease in pregnancy. In the presence of valvular heart disease, the necessary haemodynamic changes of pregnancy might cause heart failure, leading to severe maternal and fetal morbidity and even mortality. In lower-income countries, rheumatic heart disease remains one of the major causes of death related to pregnancy . In low-income countries, rheumatic heart disease is found in 60% to 80% of the pregnant women with heart disease, and 10% to 30% have a congenital disorder including congenital valve disorders . The most common valvular lesion of rheumatic heart disease is mitral stenosis. This valvular lesion can be the cause of extreme disability and even mortality during pregnancy due to an increase in the transvalvular gradient and a rise in left atrial pressure. The maternal mortality associated with mitral stenosis is stratified by New York Heart Association (NYHA) classification: class I, 0.1%; class II, 0.3%; class III, 5.5%; and class IV, 6.0%. Most patients are in class I or II at presentation, but 12% to 25% of patients are in class III or IV .
Stakisaitis, Donatas; Maksvytis, Arūnas; Salcius, Kestutis; Benetis, Rimantas
With the aim to check whether the atherogenic factors are involved in the mechanisms of valve fibrosis, we have studied the blood serum concentrations of apolipoproteins (apo) A-I and B concentration in patients suffering from rheumatic heart valve fibrosis. The quantities of apoA-I and apoB in the blood serum were tested by the ELISA method. Concentration of apoA-I and B in the blood serum was determined in rheumatic females with replacement of the damaged valves: after aortic valve operation (n=11; mean age 43.3+/-3.6 years) and after mitral valve operation (n=29; 41.3+/-4.1). The results obtained for rheumatic patients were compared with the data on age-matched healthy females (n=43; 39.5+/-5.2 years). Significantly lower apoA-I level in the blood serum of all patients suffering from rheumatic heart valve disease was determined as compared with controls: in the pooled group of patients (1.02+/-0.22 vs 1.23+/-0.23 g/l, P<0.001), in women after aortic valve replacement (0.98+/-0.21 vs. 1.23+/-0.23 g/l, P<0.005), and in women after mitral valve surgery (1.03+/-0.23 g/l vs 1.23+/-0.23 g/l, P<0.005). The apoB level in patients suffering from rheumatic heart valve disease did not differ from that of controls. The apoB/apoA-I ratio for patients with valve fibrotic damage was significantly higher as compared to controls in all groups (P<0.02). The increase of apoB/apoA-I ratio in patients with rheumatic valve fibrosis was caused by lower apoA-I levels in blood serum. The obtained results indicate that decreased apoA-I levels in blood serum can be indicative of valve fibrosis in rheumatic heart valve disease patients.
Peláez-Ballestas, Ingris; Granados, Ysabel; Silvestre, Adriana; Alvarez-Nemegyei, José; Valls, Evart; Quintana, Rosana; Figuera, Yemina; Santiago, Flor Julian; Goñi, Mario; González, Rosa; Santana, Natalia; Nieto, Romina; Brito, Irais; García, Imelda; Barrios, Maria Cecilia; Marcano, Manuel; Loyola-Sánchez, Adalberto; Stekman, Ivan; Jorfen, Marisa; Goycochea-Robles, Maria Victoria; Midauar, Fadua; Chacón, Rosa; Martin, Maria Celeste; Pons-Estel, Bernardo A
The purpose of the study is to validate a culturally sensitive adaptation of the community-oriented program for the control of rheumatic diseases (COPCORD) methodology in several Latin American indigenous populations. The COPCORD Spanish questionnaire was translated and back-translated into seven indigenous languages: Warao, Kariña and Chaima (Venezuela), Mixteco, Maya-Yucateco and Raramuri (Mexico) and Qom (Argentina). The questionnaire was administered to almost 100 subjects in each community with the assistance of bilingual translators. Individuals with pain, stiffness or swelling in any part of the body in the previous 7 days and/or at any point in life were evaluated by physicians to confirm a diagnosis according to criteria for rheumatic diseases. Overall, individuals did not understand the use of a 0-10 visual analog scale for pain intensity and severity grading and preferred a Likert scale comprising four items for pain intensity (no pain, minimal pain, strong pain, and intense pain). They were unable to discriminate between pain intensity and pain severity, so only pain intensity was included. For validation, 702 subjects (286 male, 416 female, mean age 42.7 ± 18.3 years) were interviewed in their own language. In the last 7 days, 198 (28.2 %) subjects reported having musculoskeletal pain, and 90 (45.4 %) of these had intense pain. Compared with the physician-confirmed diagnosis, the COPCORD questionnaire had 73.8 % sensitivity, 72.9 % specificity, a positive likelihood ratio of 2.7 and area under the receiver operating characteristic curve of 0.73. The COPCORD questionnaire is a valid screening tool for rheumatic diseases in indigenous Latin American populations.
Pisetsky, D S
Antinuclear antibodies (ANAs) are a diverse group of autoantibodies that bind macromolecular components of the cell nucleus. While some ANAs occur in normal individuals, others are expressed almost exclusively in patients with rheumatic disease and serve as markers for diagnosis and prognosis. Despite the clinical associations of ANAs, the relationship of these antibodies to specific disease manifestations is often unknown because the target antigens are intracellular molecules that are ubiquitously expressed. In systemic lupus erythematosus, the role of ANAs in disease manifestations is better understood, especially for antibodies to DNA and related nucleosomal antigens. These antibodies can promote nephritis by the formation of immune complexes that are deposited in the kidney. In addition, anti-DNA, along with antibodies to RNA-binding proteins such as anti-Sm, can induce non-specific immune abnormalities based on the induction of type interferon 1 by plasmacytoid dendritic cells. Despite ANA expression in rheumatic disease, studies in animal models of inflammation and tissue injury indicate that antibodies to certain nuclear molecules such as HMGB1 have protective effects. Together, these considerations suggest a function-based classification of ANAs based on their expression in normal and autoimmune individuals as well as their capacity to induce or attenuate immunological disturbances. This classification provides a framework to elucidate the serological features of rheumatic disease and the often uncertain relationship between ANA expression and disease manifestations.
Mechanistic target of rapamycin (mTOR, also known as mammalian target of rapamycin) is a ubiquitous serine/threonine kinase that regulates cell growth, proliferation and survival. These effects are cell-type-specific, and are elicited in response to stimulation by growth factors, hormones and cytokines, as well as to internal and external metabolic cues. Rapamycin was initially developed as an inhibitor of T-cell proliferation and allograft rejection in the organ transplant setting. Subsequently, its molecular target (mTOR) was identified as a component of two interacting complexes, mTORC1 and mTORC2, that regulate T-cell lineage specification and macrophage differentiation. mTORC1 drives the proinflammatory expansion of T helper (TH) type 1, TH17, and CD4−CD8− (double-negative, DN) T cells. Both mTORC1 and mTORC2 inhibit the development of CD4+CD25+FoxP3+ T regulatory (TREG) cells and, indirectly, mTORC2 favours the expansion of Tfollicular helper (TFH) cells which, similarly to DN T cells, promote B-cell activation and autoantibody production. In contrast to this proinflammatory effect of mTORC2, mTORC1 favours, to some extent, an anti-inflammatory macrophage polarization that is protective against infections and tissue inflammation. Outside the immune system, mTORC1 controls fibroblast proliferation and chondrocyte survival, with implications for tissue fibrosis and osteoarthritis, respectively. Rapamycin (which primarily inhibits mTORC1), ATP-competitive, dual mTORC1/mTORC2 inhibitors and upstream regulators of the mTOR pathway are being developed to treat autoimmune, hyperproliferative and degenerative diseases. In this regard, mTOR blockade promises to increase life expectancy through treatment and prevention of rheumatic diseases. PMID:26698023
Hurd, Kelle; Barnabe, Cheryl
We performed a systematic review designed to characterize clinical phenotypes and outcomes in Indigenous populations with rheumatic disease to enhance the understanding of how rheumatic disease presents in Indigenous populations and allow for better projection of the healthcare needs of the communities affected. A systematic search was performed in medical (Medline, EMBASE, CINAHL), Indigenous and conference abstract databases (to June 2015). Search terms for Indigenous populations were combined with terms for inflammatory arthritis conditions, connective tissue disorders, crystal arthritis and osteoarthritis. Studies were included if they reported on disease features, disease activity measures, or patient-reported outcomes in Canadian, American, Australian or New Zealand Indigenous populations. Data were extracted in duplicate, and a narrative summary was prepared. A total of 5269 titles and abstracts were reviewed, of which 504 underwent full-text review and 85 met inclusion criteria. Nearly all the studies described outcomes in the North American populations (n = 77), with only four studies from Australia and four studies from New Zealand. The majority of studies were in rheumatoid arthritis (n = 31) and systemic lupus erythematosus (n = 19). Indigenous patients with rheumatoid arthritis had higher disease activity and reported more significant impact on patient-reported outcomes and quality of life than non-Indigenous patients. Spondyloarthropathy features were described in North American populations, with most patients having advanced manifestations. In systemic lupus erythematosus, nephritis was more frequent in Indigenous populations. Gout and osteoarthritis were more severe in New Zealand Maori populations. The existing literature supports differences in disease phenotype and severity in Indigenous populations of Canada, America, Australia and New Zealand. We encourage investigators in this area of research to undertake contemporary studies that
Spitzer, Ernest; Mercado, Jorge; Islas, Fabian; Rothenbühler, Martina; Kurmann, Reto; Zürcher, Fabian; Krähenmann, Peter; Llerena, Nassip; Jüni, Peter; Torres, Pedro; Pilgrim, Thomas
The objective of the study was to evaluate the implications of different classifications of rheumatic heart disease on estimated prevalence, and to systematically assess the importance of incidental findings from echocardiographic screening among schoolchildren in Peru. We performed a cluster randomized observational survey using portable echocardiography among schoolchildren aged 5 to 16 years from randomly selected public and private schools in Arequipa, Peru. Rheumatic heart disease was defined according to the modified World Health Organization (WHO) criteria and the World Heart Federation (WHF) criteria. Among 1395 eligible students from 40 classes and 20 schools, 1023 (73%) participated in the present survey. The median age of the children was 11 years (interquartile range [IQR] 8-13 years) and 50% were girls. Prevalence of possible, probable and definite rheumatic heart disease according to the modified WHO criteria amounted to 19.7/1000 children and ranged from 10.2/1000 among children 5 to 8 years of age to 39.8/1000 among children 13 to 16 years of age; the prevalence of borderline/definite rheumatic heart disease according to the WHF criteria was 3.9/1000 children. 21 children (2.1%) were found to have congenital heart disease, 8 of which were referred for percutaneous or surgical intervention. Prevalence of RHD in Peru was considerably lower compared to endemic regions in sub-Saharan Africa, southeast Asia, and Oceania; and paralleled by a comparable number of undetected congenital heart disease. Strategies to address collateral findings from echocardiographic screening are necessary in the setup of active surveillance programs for RHD. ClinicalTrials.gov identifier: NCT02353663.
Spitzer, Ernest; Mercado, Jorge; Islas, Fabian; Rothenbühler, Martina; Kurmann, Reto; Zürcher, Fabian; Krähenmann, Peter; Llerena, Nassip; Jüni, Peter; Torres, Pedro; Pilgrim, Thomas
Background The objective of the study was to evaluate the implications of different classifications of rheumatic heart disease on estimated prevalence, and to systematically assess the importance of incidental findings from echocardiographic screening among schoolchildren in Peru. Methods We performed a cluster randomized observational survey using portable echocardiography among schoolchildren aged 5 to 16 years from randomly selected public and private schools in Arequipa, Peru. Rheumatic heart disease was defined according to the modified World Health Organization (WHO) criteria and the World Heart Federation (WHF) criteria. Findings Among 1395 eligible students from 40 classes and 20 schools, 1023 (73%) participated in the present survey. The median age of the children was 11 years (interquartile range [IQR] 8–13 years) and 50% were girls. Prevalence of possible, probable and definite rheumatic heart disease according to the modified WHO criteria amounted to 19.7/1000 children and ranged from 10.2/1000 among children 5 to 8 years of age to 39.8/1000 among children 13 to 16 years of age; the prevalence of borderline/definite rheumatic heart disease according to the WHF criteria was 3.9/1000 children. 21 children (2.1%) were found to have congenital heart disease, 8 of which were referred for percutaneous or surgical intervention. Conclusions Prevalence of RHD in Peru was considerably lower compared to endemic regions in sub-Saharan Africa, southeast Asia, and Oceania; and paralleled by a comparable number of undetected congenital heart disease. Strategies to address collateral findings from echocardiographic screening are necessary in the setup of active surveillance programs for RHD. Trial Registration ClinicalTrials.gov identifier: NCT02353663 PMID:26208006
van Tuyl, Lilian H D; Boers, Maarten
Patient-reported outcomes (PROs) are abundant in rheumatology and their numbers continue to increase. But which of the available measures are most important? Core outcome sets-including groups of domains and instruments for measuring them-have been defined for many rheumatic diseases, with the aim that all these outcomes should be measured in every clinical trial. The subgroup of PROs included in these core sets is, therefore, undoubtedly important. This Review summarizes the PROs included in core outcome sets developed for use in clinical trials across a wide range of rheumatic diseases. Three PROs are commonly utilized across the majority of rheumatic conditions: pain, physical functioning and the patient global assessment of disease activity. However, additional research is needed to fully understand the role of the patient global assessment of disease activity, to distinguish specific domains within the broad concept of health-related quality of life, and to work towards consensus on the choice between generic and disease-specific instruments in various contexts.
Allen, Marvin; Allen, John; Naseri, Take; Gardner, Rebecca; Tolley, Dennis; Allen, Lori
Echocardiography has been proposed as a method to screen children for rheumatic heart disease. The World Heart Federation has established guidelines for echocardiographic screening. In this study, we describe a rapid echocardiogram screening protocol according to the World Heart Federation guidelines in Samoa, endemic for rheumatic heart disease. We performed echocardiogram screening in schoolchildren in Samoa between 2013 and 2015. A brief screening echocardiogram was performed on all students. Children with predefined criteria suspicious for rheumatic hear diseases were referred for a more comprehensive echocardiogram. Complete echocardiograms were classified according to the World Heart Federation guidelines and severity of valve disease. Echocardiographic screening was performed on 11,434 children, with a mean age of 10.2 years; 51% of them were females. A total of 558 (4.8%) children underwent comprehensive echocardiography, including 49 students who were randomly selected as controls. Definite rheumatic heart disease was observed in 115 students (10.0 per 1000): 92 students were classified as borderline (8.0 per 1000) and 23 with CHD. Advanced disease was identified in 50 students (4.4 per 1000): 15 with severe mitral regurgitation, five with severe aortic regurgitation, 11 with mitral stenoses, and 19 with mitral and aortic valve disease. We successfully applied a rapid echocardiographic screening protocol to a large number of students over a short time period - 28 days of screening over a 3-year time period - to identify a high prevalence of rheumatic heart disease. We also reported a significantly higher rate of advanced disease compared with previously published echocardiographic screening programmes.
Wöbke, Thea K.; Sorg, Bernd L.; Steinhilber, Dieter
Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq. PMID:25071589
In the coming years the number of elderly patients with rheumatic diseases in Germany will continuously increase. Therefore, it is necessary that the structures of the healthcare system for elderly patients with rheumatic diseases are prepared for this challenge. Two important fields are of particular relevance: multimorbidity and the prevention of disability. Both points do not only affect elderly patients but are particularly important in this group. In order to solve the problems structures which facilitate interdisciplinary care should be supported. Moreover, institutions which provide rehabilitation should be utilized for the care of elderly patients with rheumatic diseases. Both can be performed in either outpatient or inpatient settings. Rheumatologists working in interdisciplinary fields, in outpatient practices, and in specialized rheumatology hospitals have key functions in the care of elderly patients with rheumatic diseases. However, practices and hospitals both have to solve the special problems of reimbursement and interfaces between the sectors.
Warnatz, K; Peter, H; Schumacher, M; Wiese, L; Prasse, A; Petschner, F; Vaith, P; Volk, B; Weiner, S
Background: Immunosuppressive treatment of rheumatic diseases may be associated with several opportunistic infections of the brain. The differentiation between primary central nervous system (CNS) involvement and CNS infection may be difficult, leading to delayed diagnosis. Objective: To differentiate between CNS involvement and CNS infection in systemic rheumatic diseases. Methods and results: Three patients with either longstanding or suspected systemic rheumatic diseases (systemic lupus erythematodes, Wegener's granulomatosis, and cerebral vasculitis) who presented with various neuropsychiatric symptoms are described. All three patients were pretreated with different immunosuppressive drugs (leflunomide, methotrexate, cyclophosphamide) in combination with corticosteroids. Magnetic resonance imaging of the brain was suggestive of infectious disease, which was confirmed by cerebrospinal fluid analysis or stereotactic brain biopsy (progressive multifocal leucoencephalopathy (PML) in two and nocardiosis in one patient). Discussion: More than 20 cases of PML or cerebral nocardiosis in patients receiving corticosteroids and cytotoxic drugs for rheumatic disease have been reported. The clinical aspects of opportunistic CNS infections and the role of brain imaging, cerebrospinal fluid analysis and stereotactic brain biopsy in the differential diagnosis are reviewed. PMID:12480669
Jetha, Arif; Badley, Elizabeth; Beaton, Dorcas; Fortin, Paul R; Shiff, Natalie J; Rosenberg, Alan M; Tucker, Lori B; Mosher, Dianne P; Gignac, Monique A M
To examine perceived independence, overprotection, and support, and their association with the employment participation of young adults with rheumatic disease. One hundred and forty-three young adults, ages 18 to 30 years, with systemic lupus erythematosus (54.5%) and juvenile arthritis (45.5%) completed a 30-min online questionnaire of their work and education experiences. Information collected was demographic, health (e.g., pain, fatigue, disease activity), work context (e.g., career satisfaction, helpfulness of job accommodation/benefits, and workplace activity limitations), and psychosocial (e.g., independence, social support, and overprotection). Log-Poisson regression analysis examined factors associated with employment status. Over half of respondents were employed (59%) and 26% were enrolled in school. Respondents reported moderate to high perceptions of independence and social support. However, 27% reported that "quite a bit" to "a great deal" of overprotection characterized their relationships with those closest to them. At the bivariate level, employed participants and those indicating greater perceived independence reported greater social support and less overprotection. Multivariable analysis revealed that being employed was associated with older age, more job accommodations/benefits perceived as being helpful, and greater perceived independence. This is one of the first studies examining the employment of young adults with rheumatic diseases. Findings highlight the importance of psychosocial perceptions such as independence and overprotection, in addition to support related to working. Additional research is needed to better understand the role of those close to young adults with rheumatic diseases in supporting independence and encouraging employment.
Bañuelos-Ramírez, David; Cedillo-Ramírez, María L; Yáñez-Santos, Jorge A
Living beings and the environment that supports them have a mutual interdependence and therefore any event that occurs within an ecosystem affects all parts. The influence that the environment has on subjects that maydevelop an illness has been amply recognized. For some autoimmune diseases such as systemic lupus erythematosus (SLE), the possibility of its development under ultraviolet light and prolonged exposure to sunlight has been recognized. Microorganisms may activate other illnesses such as reactive arthritis. Substances such as alfalfa are also able to unleash disease activity. Laboratory workers who manipulate sera of patients with autoimmune rheumatic disorders develop antibodies to the sera that they are working with. It is thus that environmental sciences and focused research allow the development of a new approach to the study of possible pathogenic mechanisms in the appearance of certain rheumatic disorders. This article reviews the main existing evidence and proposes certain hypotheses derived from it.
Gao, Y; Liu, X; Zhang, L; Xia, T; Zhao, D
Academic contributions by Chinese scholars have grown to take second place worldwide since 2009. However, little was known about Chinese academic contributions and their influence on rheumatic diseases. In order to present an overview of this field, a comprehensive bibliometrics analysis was performed based on data from two databases up to 2015. Since 2013, China has occupied third place regarding the number of rheumatic diseases' publications. Nevertheless, most of these articles were not associated with high impact factors or frequent citations, let alone great influence. Multidisciplinary teams are being formed. Although on the right track, more efforts in all aspects are needed to improve developments in the area of rheumatology in China.
Taran, A I; Puzanova, O G; Lapenko, O Ie; Sol's'kyĭ, V I; Samoĭlova, S M
In the article, errors that are frequently encountered in dealing with rheumatic diseases are analysed together with the experience gained by the authors themselves with the management of 380 patients using local injections of corticosteroids (diprospan) and chondroprotectors (alflutop). The employment of local injection therapy has been shown to shorten considerably the patient's hospital stay, to improve the quality of life of the patients, with them being practically free from ill effects and complications.
Fengming, Yi; Jianbing, Wu
Inflammatory bowel disease (IBD) is a chronic disease mostly involved with intestine with unknown etiology. Diagnosis, evaluation of severity, and prognosis are still present as challenges for physicians. An ideal biomarker with the characters such as simple, easy to perform, noninvasive or microinvasive, cheap, rapid, and reproducible is helpful for patients and clinicians. Currently biomarkers applied in clinic include CRP, ESR, pANCA, ASCA, and fecal calprotectin. However, they are far from ideal. Lots of studies are focused on seeking for ideal biomarker for IBD. Herein, the paper reviewed recent researches on biomarkers of IBD to get advances of biomarkers in inflammatory bowel disease. PMID:24963213
Liu, Yan-Cun; Zou, Xian-Biao; Chai, Yan-Fen; Yao, Yong-Ming
Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases.
Wan, Joy; Imadojemu, Sotonye; Werth, Victoria P
The treatment of rheumatic and autoimmune skin disease in women who are pregnant or of childbearing potential can present challenges to the dermatologist. We discuss the current approaches to treating lupus erythematosus, antiphospholipid antibody syndrome, dermatomyositis, morphea and systemic sclerosis, mixed connective tissue disease, rheumatoid arthritis, and autoimmune blistering disease in such patients. In the appropriate setting, topical and systemic corticosteroids, hydroxychloroquine, dapsone, azathioprine, and ultraviolet B phototherapy may be safely and cautiously used during pregnancy. Considerations about contraception, planned conception, therapeutic options, and disease control are paramount in optimizing pregnancy outcomes and minimizing risks to both mother and fetus.
Wilson, J. H. P.
Intestinal inflammation is controlled by various immunomodulating cells, interacting by molecular mediators. Neuropeptides, released by enteric nerve cells and neuroendocrine mucosa cells, are able to affect several aspects of the general and intestinal immune system, with both pro- as well as anti-inflammatory activities. In inflammatory bowel disease (IBD) there is both morphological as well as experimental evidence for involvement of neuropeptides in the pathogenesis. Somatostatin is the main inhibitory peptide in inflammatory processes, and its possible role in IBD is discussed. PMID:18472863
Ogimi, Chikara; Tanaka, Risa; Saitoh, Akihiko; Oh-Ishi, Tsutomu
Children with rheumatic diseases receiving immunosuppressive therapy are a high-risk group for influenza virus infection; however, few data are available regarding the efficacy and safety of influenza vaccine for those individuals. This was a prospective study evaluating the immunogenicity and safety of influenza vaccine in 49 children (mean ± standard deviation: 12.1 ± 4.8 years, age range: 0-21 years) with pediatric rheumatic diseases including juvenile idiopathic arthritis (n = 23), systemic lupus erythematosus (n = 12), juvenile dermatomyositis (n = 6), and others (n = 8), who were receiving immunosuppressive therapies. A total of 36 healthy children were selected as a control. The influenza virus type-A and B antibody titers were measured using hemagglutinin inhibition before and after the vaccination. There were no significant differences in the percentage of vaccine recipients with an increase in the serum titers ≥ 4× after vaccination (H1N1, H3N2, and B strain) between the 2 groups (P = 0.49, P = 0.25, P = 0.56, respectively), demonstrating similar immunogenicity of the influenza vaccination between patients and control groups. There were no serious adverse effects related to the vaccine in either group. In the children with pediatric rheumatic diseases receiving immunosuppressive agents, influenza vaccination resulted in serum antibody titers similar to those in the controls without major adverse effects. Such children receiving immunosuppressive therapy are a high-risk group for influenza virus infection, therefore vaccine should be given.
Duarte, Ana Catarina; Santos-Faria, Daniela; Gonçalves, Maria João; Sepriano, Alexandre; Mourão, Ana Filipa; Duarte, Cátia; Neves, Joana Sousa; Águeda, Ana Filipa; Ribeiro, Pedro Avila; Daniel, Alexandra; Neto, Adriano; Cordeiro, Ana; Rodrigues, Ana; Barcelos, Anabela; Silva, Cândida; Ponte, Cristina; Vieira-Sousa, Elsa; Teixeira, Filipa; Oliveira-Ramos, Filipa; Araújo, Filipe; Barcelos, Filipe; Canhão, Helena; Santos, Helena; Ramos, João; Polido-Pereira, Joaquim; Tavares-Costa, José; Melo Gomes, José António; Cunha-Miranda, Luís; Costa, Lúcia; Cerqueira, Marcos; Cruz, Margarida; Santos, Maria José; Bernardes, Miguel; Oliveira, Paula; Abreu, Pedro; Figueira, Ricardo; Barros, Rita; Falcão, Sandra; Pinto, Patrícia; Pimenta, Sofia; Capela, Susana; Teixeira, Vitor; Fonseca, João Eurico
Methotrexate (MTX) is the first-line drug in the treatment of rheumatoid arthritis (RA) and the most commonly prescribed disease modifying anti-rheumatic drug. Moreover, it is also used as an adjuvant drug in patients under biologic therapies, enhancing the efficacy of biologic agents. To review the literature and update the Portuguese recommendations for the use of MTX in rheumatic diseases first published in 2009. The first Portuguese guidelines for the use of MTX in rheumatic diseases were published in 2009 and were integrated in the multinational 3E Initiative (Evidence Expertise Exchange) project. The Portuguese rheumatologists based on literature evidence and consensus opinion formulated 13 recommendations. At a national meeting, the recommendations included in this document were further discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the updated recommendations. Results presented in this article are mainly in accordance with previous guidelines, with some new information regarding hepatitis B infection during MTX treatment, pulmonary toxicity monitoring, hepatotoxicity management, association with hematologic neoplasms, combination therapy and tuberculosis screening during treatment. The present recommendations combine scientific evidence with expert opinion and attained desirable agreement among Portuguese rheumatologists. The regular update of these recommendations is essential in order to keep them a valid and useful tool in daily practice.
Thornton, Judith; Rangaraj, Satyapal
Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy and hypertrophic osteoarthropathy. Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its treatment. To review the effectiveness and safety of disease-modifying anti-rheumatic drugs (DMARDs) for the management of arthritis related to cystic fibrosis in adults and children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database handsearches of relevant journal and abstract books of conference proceedings.Date of most recent search: May 2008 Randomised controlled trials which compared the efficacy and safety of DMARDs (e.g. methotrexate, gold, sulfasalazine, penicillamine, leflunomide, hydroxychloroquine and newer agents such as biologic disease modifying agents and monoclonal antibodies) with each other, with no treatment or with placebo for cystic fibrosis-related arthropathy or hypertrophic osteoarthropathy. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that cystic fibrosis-related arthritis can be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. But when episodic symptoms progress to persistent disease, DMARDs may be needed to limit the course of the disease. It is disappointing that no randomised controlled trials to rigorously evaluate DMARDs could be found. This systematic review has identified the need for a well-designed adequately powered randomised controlled trial to assess the efficacy and safety of DMARDs for the management of cystic fibrosis-related arthropathy and hypertrophic osteoarthropathy in adults and children with
... Inflammatory Bowel Disease? Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). Symptoms include abdominal ... become pregnant? Women with ulcerative colitis and inactive Crohn’s disease are as likely to become pregnant as women ...
Gupta, Usha; Mir, Snober S; Srivastava, Apurva; Garg, Naveen; Agarwal, Surendra K; Pande, Shantanu; Mittal, Balraj
Rheumatic heart disease (RHD) is the most serious complication of heart that comprises inflammatory reactions in heart valves. Cytokines play a critical role in triggering inflammatory reactions and they activate the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway. Altered signals of STATs play important roles in the balance between proinflammatory and anti-inflammatory cytokines in inflammatory diseases. The aim of the present study was to investigate for the association of polymorphisms related with STAT genes, i.e. STAT3 (rs4796793 C/G) and STAT5b (rs6503691 C/T) with the pathogenesis of RHD. This case-control association study involved 300 healthy controls and 400 RHD patients from North Indian Population. We categorized RHD patients into two subgroups based on involvement of heart valves, mitral valve lesion alone (MVL), and combined valve lesions including mitral valve (CVL). Genotyping was done by RFLP/Taqman probes. We observed that STAT3 CG and GG genotypes were significantly associated with RHD (p=0.030 and p=0.014 respectively), STAT5b CT and TT genotypes were also significantly associated with RHD (p≤0.001). Haplotype analysis revealed that minor alleles of both the variants (Grs4796793Trs6503691) were significantly associated (p<0.0001) with increased risk of the disease susceptibility irrespective of gender or age of onset of the disease. However, the polymorphisms were not involved in severity of RHD as both MVL and CVL patients were equally affected. STAT Grs4796793Trs6503691 carriers may have reduced production of STAT3 leading to damage of heart valves. Thus, STAT genes polymorphisms may be useful markers for the identification of individuals with high risk of RHD in the susceptible population. Copyright © 2014 Elsevier B.V. All rights reserved.
Cuende, José I; Pérez de Diego, Ignacio J; Godoy, Diego
More than a century of research has shown that atherosclerosis is an inflammatory process more than an infiltrative or thrombogenic process. It has been demonstrated epidemiologically and by imaging techniques, that systemic inflammatory diseases (in particular, but not exclusively, rheumatoid arthritis and systemic lupus erythematosus) increase the atherosclerotic process, and has a demonstrated pathophysiological basis. Furthermore, treatments to control inflammatory diseases can modify the course of the atherosclerotic process. Although there are no specific scales for assessing cardiovascular risk in patients with these diseases, cardiovascular risk is high. A number of specific risk scales are being developed, that take into account specific factors such as the degree of inflammatory activity. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.
Pătraşcu, I V; Ghenoiu, O; Tache, M
Serum samples from 95 patients with rheumatoid arthritis, 24 patients with other various rheumatic diseases, 50 patients with diabetes mellitus, 34 patients with acute viral infections, 6 patients with infectious mononucleosis, 77 patients with lymphomas and leukemia and 110 blood donors and 24 healthy subjects as normal controls, respectively, were tested by indirect immunofluorescence (IF) reaction for the presence of specific antibodies against Epstein-Barr virus determined viral capsid antigen (anti-VCA) and Epstein-Barr active viral infection. The IF test carried out in acetone-fixed smears of EB-3 cell line revealed EB antibodies anti-VCA in 83.3% of infectious mononucleosis, 61.0% lymphomas and leukemia, 58.0% diabetic patients. The frequency of anti-VCA antibodies in rheumatic patients was 31.4%, and 3.6% and 25% in sera from blood donors and healthy subjects, respectively. Incidence of active EBV infection was 5.7% of rheumatic diseases, 17.7% of acute virus inf