Current Opinion In Rheumatology Research Articles

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Cees G.M. KallenbergCees G.M. KallenbergCees G.M. Kallenberg, MD, graduated from the Medical School of the University of Leiden, The Netherlands. He was registered as an internist in 1980 and successfully completed his PhD studies on “Raynaud's Phenomenon and Systemic Autoimmune Disease” in 1982 at the University Medical Center, Groningen, The Netherlands. He was appointed as Associate Professor in Internal Medicine - Clinical Immunology in 1985 and as full professor in 1993. He has chaired the Department of Rheumatology and Clinical Immunology at the Groningen University, The Netherlands, until May 1, 2011. His main research is on systemic autoimmune diseases, in particular ANCA-associated vasculitides, systemic lupus erythematosus, and sjögren's syndrome. He has written more than 500 articles on these subjects in international peer-reviewed journals. He is an invited speaker on his research topics at all major international meetings, and is an editorial board member of several journals in clinical immunology, nephrology and rheumatology. Ronald F. van VollenhovenRonald F. van VollenhovenProfessor Ronald F. van Vollenhoven is chief of the Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID) at the Karolinska Institute, and of the Clinical Trials Unit Rheumatology at the Karolinska University Hospital, Sweden. He received his MD and PhD degrees from the University of Leiden, The Netherlands. After graduating in 1984 he pursued immunology research at Cornell Medical College, New York, USA, followed by residency (specialty training) in internal medicine at the State University of New York at Stony Brook, USA, and a fellowship in rheumatology at Stanford University in Palo Alto, USA, following which he received an American Board of Internal Medicine certification in both internal medicine and rheumatology. From 1993 to 1998 Dr van Vollenhoven held a faculty appointment as Assistant Professor of Medicine in the Division of Immunology and Rheumatology at Stanford University, USA, and from 1995 he was the Medical Services Chief and Fellowship Director in that division. In 1998 Dr van Vollenhoven moved to Stockholm, Sweden, where he worked as a Senior Physician and Chief of the Clinical Trials Unit in the Department of Rheumatology at the Karolinska University Hospital and Associate Professor of Rheumatology; and in 2010, he was appointed in his current position at the Karolinska Institute. Dr van Vollenhoven's research interests focus around the development and systematic evaluation of biological and immunomodulatory treatments for the rheumatic diseases. With his co-workers, he has established the Stockholm registry for biological therapies (the STURE database) for this purpose, which has supported research projects relating to clinical efficacy, pharmacology, outcomes and pharmacoeconomics. He has been principal investigator in many clinical trials of novel therapies in rheumatic diseases and has contributed to a number of important investigator-initiated trials including the recently published SWEFOT trial. He has published over 150 original papers, book chapters and reviews, and is editor of the textbook Targeted Treatment of the Rheumatic Diseases. In 2004, Dr van Vollenhoven was awarded the Scandinavian Research Foundation Prize for excellence in clinical research in rheumatology. He is a member of several editorial boards and the EULAR scientific programme committee, chair of the Swedish health economics working group HeraS, and co-founder of the IRBIS registry for biologics in SLE and of the NORD-STAR collaboration for Nordic trials in the rheumatic diseases.

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. Section Editors John VargaJohn VargaJohn Varga is the John and Nancy Hughes Distinguished Professor in Rheumatology at Northwestern University in Chicago, Illinois, USA. Born in Budapest, Hungary, Dr Varga graduated from Columbia University in New York, USA and completed his medical studies at New York University, USA. He undertook Rheumatology training at Boston University, USA followed by a research fellowship at the University of Pennsylvania, USA with Professor Sergio Jimenez. In 2004, he joined the faculty of the Feinberg School of Medicine in Chicago, USA, where he directs the multi-disciplinary Northwestern Scleroderma Program. His research focuses on the pathogenesis and treatment of scleroderma and fibrosis combining clinical and laboratory-based investigation. Dr Varga is the author of more than 240 original articles, 40 book chapters and 3 books. His research has been funded by the National Institutes of Health, the Department of Defense and the Scleroderma Research Foundation. In 2007, he was elected a member of the Association of American Physicians. Lisa Christopher-StineLisa Christopher-StineLisa Christopher-Stine is Assistant Professor of Medicine and Neurology at the Johns Hopkins University School of Medicine in Baltimore, USA. She is a graduate of Franklin and Marshall College, USA where she was inducted into Phi Beta Kappa, graduating cum laude. She attended medical school at Hahnemann University in Philadelphia, USA where she was inducted into the Alpha Omega Alpha (AOA) Medical Honor Society. She later completed her internal medicine training at MCP Hahnemann University Hospitals and was chosen as Chief Resident. She joined the Johns Hopkins Division of Rheumatology after completing her Rheumatology Fellowship at The Johns Hopkins University, USA in June, 2003. She was awarded a Master's degree in Public Health from the Johns Hopkins Bloomberg School of Public Health in 2004. She is currently the Co-Director of The Johns Hopkins Myositis Center, a multidisciplinary clinic formally established in 2007 on the Johns Hopkins Bayview campus. Dr Christopher-Stine is utilizing her training in epidemiology and biostatistics to develop improved diagnostic and classification criteria for the idiopathic inflammatory myopathies. She has established a prospective myositis cohort at Johns Hopkins Hospital to undertake longitudinal cohort studies and to initiate future intervention protocols for patients with autoimmune myopathies. She is also the principal investigator or co-principal investigator for the myositis clinical trials taking place at Johns Hopkins. Dr Christopher-Stine's other research interest includes the etiology of statin-associated myotoxicity for which she has written medical reviews and recently, along with her colleagues, described a new form of immune-mediated necrotizing myopathy where HMGCoA Reductase serves as the autoantigenic target and is strongly linked to statin therapy. She currently serves as President of The Maryland Society for Rheumatic Diseases (MSRD), Maryland's state professional organization of rheumatologists and allied health professionals and is listed in Castle-Connolly's America's Top Doctor's.

Current World Literature

Current Opinion in Rheumatology: January 2011 - Volume 23 - Issue 1 - p 125-130 doi: 10.1097/BOR.0b013e3283422cce

Henoch–Schönlein purpura

To provide an update on recent advances in the genetic susceptibility, pathogenesis and treatment of Henoch-Schönlein purpura. Recent work has advanced our understanding of the genetic susceptibility and pathogenesis of Henoch-Schönlein purpura, but there are still significant gaps in our knowledge. Information concerning the most effective treatment of Henoch-Schönlein purpura has begun to emerge. Corticosteroid therapy reduces the duration and severity of abdominal and joint pain, but corticosteroids do not prevent the development of nephritis, or alter the natural history of Henoch-Schönlein purpura. The most effective treatment for severe nephritis remains unclear despite multiple, mostly retrospective reports investigating a variety of drugs. Despite recent progress, our understanding of the genetic susceptibility, pathogenesis and treatment of Henoch-Schönlein purpura remains incomplete. Further research is necessary in order to clearly define the genetic susceptibility and the pathogenesis of Henoch-Schönlein purpura. Multicenter clinical trials are needed to determine the most effective treatment of Henoch-Schönlein purpura, particularly for patients with severe nephritis.

Current World Literature

Current Opinion in Rheumatology: July 2010 - Volume 22 - Issue 4 - p 456-470 doi: 10.1097/BOR.0b013e32833bc2a5

Kawasaki Disease

Kawasaki disease (KD) is an acute systemic inflammatory illness that occurs predominately in children <5 years of age. The reported incidence varies widely depending on the ethnicity of the population and the method of case ascertainment. Recent reports would suggest the annual incidence is ≈20 to 25 per 100 000 children <5 years of age in North America, with the highest reported incidence of 188 being in Japan, where the disease was first described in 1967.1 The illness is self-limited and of unknown cause, but is complicated by a systemic vasculitis with a predilection for small- to medium-sized arteries, particularly the coronary arteries. The majority of patients will have either transient coronary artery dilation or no coronary artery luminal changes as noted on echocardiography. Long-term prognosis for these patients is considered to be excellent. Coronary artery aneurysms occur in 25% of patients, but the prevalence is reduced to ≈4% for patients treated with intravenous immunoglobulin infusion within 10 days of illness onset. Aneurysms are associated with an intense inflammatory cell infiltrate, destruction of the internal elastic lamina, and smooth muscle cell death. Coronary artery involvement is usually maximal within 6 to 8 weeks after the acute episode. Regression of aneurysms can occur primarily through myointimal proliferation, although the arterial structure and function remains abnormal,2 and there is an important ongoing risk of stenoses and occlusions.3 Long-term cardiology assessment and management is required, and some of these patients may require revascularization procedures or, rarely, cardiac transplantation. KD has become the most prevalent acquired cardiac disease in children in developed countries. Article see p 60 Although coronary artery complications are the predominant cause of morbidity and mortality, other cardiovascular abnormalities can occur. Valvulitis is a less prevalent complication, and there have been case reports of important long-term aortic and …

Current World Literature

Current Opinion in Rheumatology: July 2008 - Volume 20 - Issue 4 - p 491-518 doi: 10.1097/BOR.0b013e32830901b0

Current World Literature

Current Opinion in Rheumatology: January 2008 - Volume 20 - Issue 1 - p 111-120 doi: 10.1097/BOR.0b013e3282f408ae

CD163-Mediated Hemoglobin-Heme Uptake Activates Macrophage HO-1, Providing an Antiinflammatory Function

See related article, pages 943–950 A study by Schaer et al,1 which appears in this issue of Circulation Research , provides evidence suggesting that CD163 acts as a hemoglobin (Hb) transporter and, via activation of macrophages, heme oxygenase-1 (HO-1) provides antiinflammatory activity, presumably by an increase in ferritin. Induction of HO-1 was observed to occur when the cultured macrophages, endothelial cells or tubular cells were exposed to heme or hemoglobin (for a review see Abraham and Kappas2). Heme and denatured hemoglobin toxicity play an important role in a broad spectrum of pathological circumstances such as myocardial ischemia, hypertension, cardiomyopathy, reperfusion, organ transplantation, pulmonary disorders, and inflammation among others.3 In the cell free system, hemoglobin is bound to haptoglobin before clearance by the macrophage hemoglobin scavenger receptor CD163. Schaer et al1 demonstrated that CD163-hemoglobin transport is regarded as a critical step in the hemoglobin clearance pathway in the macrophage, especially under conditions of extreme hemoglobin release resulting from hemolysis. Binding hemoglobin-haptoglobin to CD163 cells also elicits IL-10 secretion, which contributes to the induction of HO-1.4 Thus, CD163 has a functional role as an antioxidant by enhancing HO-1, the major cytoprotective response. This links heme transport directly to a known receptor with well characterized endocytic properties and signaling functions.5 Heme-hemopexin is also taken up by LRP/CD91 and, as such, may inhibit inflammatory functions in phagocytic and antiinflammatory macrophages; however, a link to functional HO-1 was not described. Schaer et al1 demonstrated that induction of HO-1 by Hb is functionally linked to CD163 and, using gene array analysis, were able to show that Hb elicits a noninflammatory transcriptional response in macrophages, presumably by the coordinated increase in ferritin synthesis following the activation of HO-1. This response was mediated by CD163 and did not involve the …

The environment-autoimmune link.

ArticleOpen AccessNIEHS News May 2003 E Hood E Hood Search for more papers by this author Published:1 May 2003https://doi.org/10.1289/ehp.111-a274Cited by:2AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit FiguresReferencesRelatedDetailsCited by (2004) Chapter 3 Health consequences of immunotoxic effects Immunotoxicology of Drugs and Chemicals: an Experimental and Clinical Approach - Volume I: Principles and Methods of Immunotoxicology, 10.1016/S1873-9822(04)80004-2, (55-126), . Chinoy H, Ollier W and Cooper R (2004) Have recent immunogenetic investigations increased our understanding of disease mechanisms in the idiopathic inflammatory myopathies?, Current Opinion in Rheumatology, 10.1097/01.bor.0000142339.24380.b7, 16:6, (707-713), Online publication date: 1-Nov-2004. Vol. 111, No. 5 May 2003Metrics About Article Metrics Publication History Originally published1 May 2003Published in print1 May 2003 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

T-cell-dependent pathways in rheumatoid arthritis.

Two theories, not necessarily mutually exclusive, attempt to explain the pathogenesis of rheumatoid arthritis. The mesenchymal hypothesis proposes that, after an initial event triggered by T cells, synovitis is maintained by autocrine and paracrine pathways involving macrophages and synovial fibroblasts. The T-cell hypothesis proposes that T cells are continuously involved in the pathogenesis of rheumatoid arthritis from its initiation phase through to the chronic stage. This paper reviews recent work in this area and concludes that there is substantial evidence in support of the T-cell hypothesis.

Differences in clinical presentation and outcome in different countries for Takayasuʼs arteritis

Takayasu's arteritis is a chronic vasculitis, the etiology of which is still unknown. This condition involves primarily the aorta, its main branches, and the coronary and pulmonary arteries. One epidemiologic characteristic of this morbid condition is that almost all patients come from Asian and South American countries, which has led to searches in the role of genetic factors in its pathogenesis. International surveys on HLA analysis have focused on HLA-B52 and B39 disequilibrium with this morbid condition. These comparative studies have made clear the different characteristic clinical manifestations among Asian and South American countries, which will prompt further studies in relation to genetic factors in the future.

Current Opinion in RHEUMATOLOGY

Current Opinion in RHEUMATOLOGY

Systemic lupus erythematosus and Sjögrenʼs syndrome

Audie L. Murphy Memorial Veterans Hospital and University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Current Opinion in Rheumatology 1993, 5:547-548

Animal models of bone physiology

Because of the well-known technical difficulties in investigating the histology and physiology of the skeleton, bone physiology is not yet completely understood. Much new information has been obtained in recent years with in vitro investigations, but animal models are widely used when the overall effects of hormones or therapeutic agents or both need to be investigated. In this review, we discuss results obtained over the past year on several not yet completely understood topics. The effect of exercise on bone mass has been stressed by several authors, and at the cellular level, it has been suggested that the inositol cascade is the intracellular transduction pathway for mechanical stimuli. Ovariectomized rat systems have been widely used to demonstrate the protective effect of estrogen against bone resorption, and interesting indications of an estrogen-dependent stimulation of bone formation have been presented. The anabolic effect of low doses of fluoride has also been assessed.

Immunosuppressive drug therapy for rheumatic disease.

The role of intravenous and oral cyclophosphamide in treating systemic lupus and Wegener's granulomatosis was examined in several large studies during the past year. Oral cyclophosphamide for 2 months followed by prednisone alone was relatively ineffective in preventing disease progression in lupus nephritis patients with initially abnormal serum creatinine values. A controlled trial in which three regimens for treating lupus nephritis were compared resulted in superiority of long-term intravenous cyclophosphamide therapy over pulse prednisone or short-term intravenous cyclophosphamide. Two open studies describe treatment of neuropsychiatric lupus with pulse cyclophosphamide. Patients with clinical evidence of inflammatory disease of the central nervous system appeared to respond to this therapy even if antiphospholipid antibodies were present. Analysis of a large cohort of patients with Wegener's granulomatosis showed a high incidence of cancer at long-term follow-up as well as a high incidence of recurrence, often several years after induction of remission with cyclophosphamide plus prednisone. Much progress was made in defining the mechanisms of action of cyclosporine. Additional studies examine the role of cyclosporine in necrotizing scleritis complicating rheumatoid arthritis. Concomitant administration of nonsteroidal anti-inflammatory drugs and cyclosporine to rheumatoid arthritis patients resulted in increased short-term deterioration of renal function. Studies of patients with various autoimmune diseases showed an association of the mean, maximal, and cumulative doses of cyclosporine with biopsy-proven nephropathy. Cytarabine was tried at low doses in the treatment of rheumatoid arthritis with improvement in some patients.

Tumors of soft tissues and bone.

The recent literature pertaining to tumors of articular structures and bone is reviewed. In pigmented villonodular synovitis, the bone resorptive cell is a macrophage polykaryon rather than an osteoclast. Complete arthroscopic synovectomy was successful in most diffuse articular forms of the disease. The early synovial changes in synovial chondromatosis were described; the lesion may be difficult to distinguish from synovial chondrosarcoma. Free body removal may be sufficient to treat synovial chondromatosis. Magnetic resonance imaging has been found useful in association with plain radiographs in the diagnosis of hemangioma and synovial sarcoma. Intracapsular osteoid osteoma, a benign neoplasm, may cause chronic monoarthritis. Computed tomography is essential in the diagnosis of this lesion. Aneurysmal bone cysts frequently show fluid-fluid levels on magnetic resonance imaging. Osteosarcoma, predominantly a tumor of childhood or adolescence, may occur in individuals over age 40 with underlying bone conditions. Computed tomography and magnetic resonance imaging are complementary in defining the extent of this lesion.

Rheumatoid arthritis

Stanford University School of Medicine, Stanford, California, USA Current Opinion in Rheumatology 1993, 5:167-168

Malignant hyperthermia and associated disorders.

Malignant hyperthermia is a pharmacogenetic disorder of skeletal muscle that may cause a life-threatening reaction during administration of general anesthesia. It is inherited in an autosomal dominant pattern and, at least in some families, is caused by a mutation in the ryanodine receptor-calcium-release channel gene on chromosome 19. Malignant hyperthermia displays heterogeneity, making the development of a simple screening test difficult. Malignant hyperthermia may be caused by other biochemical defects affecting intramyoplasmic calcium. Some myopathies, such as central core disease, are frequently associated with malignant hyperthermia susceptibility. In other myopathies, like Duchenne muscular dystrophy, unusual compensatory mechanisms may produce a hypermetabolic state identical to that of malignant hyperthermia.

The eosinophilia-myalgia syndrome and eosinophilic fasciitis

Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA Current Opinion in Rheumatology 1990, 2:960-966