DOCSLIB.ORG

Scleroderma Phenotype'' This Information Is Current As of September 27, 2021

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Scleroderma Phenotype'' This Information Is Current As of September 27, 2021 Autoantibodies to Fibrillin-1 Activate Normal Human Fibroblasts in Culture through the TGF-β Pathway to Recapitulate the ''Scleroderma Phenotype'' This information is current as of September 27, 2021. Xiaodong Zhou, Filemon K. Tan, Dianna M. Milewicz, Xinjian Guo, Constantin A. Bona and Frank C. Arnett J Immunol 2005; 175:4555-4560; ; doi: 10.4049/jimmunol.175.7.4555 http://www.jimmunol.org/content/175/7/4555 Downloaded from References This article cites 32 articles, 11 of which you can access for free at: http://www.jimmunol.org/content/175/7/4555.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 27, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Autoantibodies to Fibrillin-1 Activate Normal Human Fibroblasts in Culture through the TGF-␤ Pathway to Recapitulate the “Scleroderma Phenotype”1 Xiaodong Zhou,2* Filemon K. Tan,* Dianna M. Milewicz,† Xinjian Guo,* Constantin A. Bona,‡ and Frank C. Arnett* Fibroblasts from patients with systemic sclerosis (SSc) are activated producing excessive amounts of extracellular matrix (ECM) components. Recently, we identified a new SSc-specific autoantibody against portions of fibrillin-1, a major component of ECM microfibrils and regulator of TGF-␤1 signaling. To examine a potential pathogenic role of anti-fibrillin-1 autoantibodies, normal human fibroblasts were treated with affinity-purified autoantibodies isolated from SSc sera and then examined for alterations in gene and protein expression levels using microarrays, quantitative RT-PCR, immunoblots, and immunofluorescence. Compared Downloaded from with fibroblasts cultured in normal medium or in medium containing normal human IgG, anti-fibrillin-1 autoantibody-treated normal dermal fibroblasts showed increased expression of COL and several other ECM components characteristically overex- pressed in SSc fibroblasts. This was accompanied by phosphorylation and nuclear translocation of Smad3. Neutralization of TGF-␤1 with anti-TGF-␤1 Abs significantly diminished the activation of fibroblasts by anti-fibrillin-1 autoantibodies. These data indicate that anti-fibrillin-1 autoantibodies can induce the activation of normal dermal fibroblasts into a profibrotic phenotype resembling that of SSc by potentially causing the release of sequestered TGF-␤1 from fibrillin-1-containing microfibrils in the http://www.jimmunol.org/ ECM. The Journal of Immunology, 2005, 175: 4555–4560. cleroderma or systemic sclerosis (SSc)3 is a chronic, mul- turn phosphorylates Smad3. Phosphorylated Smad3 (p-Smad3) tisystem disease characterized by widespread cutaneous translocates to the nucleus to activate transcription of target genes S and visceral fibrosis. Although the etiopathogenesis of SSc in the nucleus, such as COL (3). Furthermore, turnover of the ECM is unknown, it is believed to be a complex disorder of autoimmune components in SSc also appears to be influenced by a family of origin based on familial and clinical overlap with other autoim- matrix metalloproteinases (MMP), along with tissue inhibitors of mune diseases and the presence of circulating, highly disease-spe- MMP (TIMP) (4). by guest on September 27, 2021 cific autoantibodies to nuclear and nucleolar Ags (1). Pathological Recently, we have demonstrated that microsatellite and single findings in clinically affected SSc skin indicate that fibroblasts are nucleotide polymorphisms in and around the fibrillin-1 gene activated to produce excessive amounts of collagens (COL) and (FBN1) on chromosome 15q are associated with susceptibility to other extracellular matrix (ECM) components, likely via activation SSc (5, 6). A partial, in-frame duplication of the same gene ( fbn1) of TGF-␤-dependent pathways (2). The ligand TGF-␤ binds the is the cause of the tight skin (tsk) phenotype in a murine model of TGF-␤ transmembrane receptor complex and induces phosphory- human SSc (7). Fibrillin-1 is the major constituent of 10- to 12-nm lation of TGF-␤RI by the TGF-␤RII (TGFBRII) kinase, which in microfibrils in the ECM and recently has been demonstrated to be an important regulator of TGF-␤ (8). Mutations in FBN1 are † *Division of Rheumatology and Clinical Immunogenetics and Division of Medical known to cause Marfan syndrome, an autosomal dominant condi- Genetics, Department of Internal Medicine, University of Texas-Health Science Cen- ter, Houston, TX 77030; and ‡Department of Microbiology, Mount Sinai Medical tion characterized by skeletal, ocular, and cardiovascular compli- School, New York, NY 10029 cations (9). In cultured fibroblasts from SSc patients, fibrillin-1 is Received for publication March 31, 2005. Accepted for publication July 12, 2005. synthesized and secreted normally into the ECM, but the fibrillin- The costs of publication of this article were defrayed in part by the payment of page 1-containing microfibrils are unstable and turn over more rapidly charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. when compared with microfibrils from control fibroblasts (10). 1 This work was supported by National Institutes of Health-National Institute of Ar- First-degree relatives of patients with SSc also have the same mi- thritis and Musculoskeletal and Skin Diseases Specialized Center of Research in crofibril instability, suggesting that this is an inherent genetic de- Scleroderma Grant (IP50AR44888; to F.C.A.), National Institutes of Health National fect (11). Theoretically, a breakdown of fibrillin-1-containing mi- Center for Research Resources 3M01-RR-02558-12S1 (to F.K.T.), National Institutes of Health R01AR46718 (to D.M.M.), Scleroderma Foundation and National Institutes crofibrils could lead to release of TGF-␤ sequestered in of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases microfibrils (8). In addition, neoepitopes of unstable fibrillin-1 1R03AR050517-01A2 (to X.Z.) and M01RR02558 (General Clinical Research Center). could be revealed to the immune system resulting in an autoim- 2 Address correspondence and reprint requests to Dr. Xiaodong Zhou, Division of mune response. Indeed, we have recently found that a significant Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, Uni- fraction of SSc patients have circulating autoantibodies to portions versity of Texas-Health Science Center, 6431 Fannin, MSB5.270, Houston, TX 77030. E-mail address: [email protected] of fibrillin-1, which are SSc-specific (12–14). These autoantibod- 3 Abbreviations used in this paper: SSc, systemic sclerosis; ECM, extracellular ma- ies were detected with a recombinant peptide expressing the pro- trix; MMP, matrix metalloproteinase; TIMP, tissue inhibitors of MMP; COL, colla- line-rich region of fibrillin-1 (12, 13). Interestingly, the tsk mouse gen; CTGF, connective tissue growth factor; TGFBRII, TGF-␤R II; LTBP, latent also has been found to produce anti-fibrillin Abs as well (15). TGF-␤ binding protein; p-Smad3, phosphorylated Smad3; LAP, latent-associated peptide. Therefore, we tested the hypothesis that affinity-purified human Copyright © 2005 by The American Association of Immunologists, Inc. 0022-1767/05/$02.00 4556 PROFIBROTIC ROLES OF ANTI-FIBRILLIN-1 AUTOANTIBODIES autoantibodies to fibrillin-1 from SSc patients might induce acti- Indirect immunofluorescene vation of normal human dermal fibroblasts using microarray After a 24-h treatment with affinity-purified anti-fibrillin-1 autoantibodies, screening of ECM gene expression profiles and quantitative RT- normal human IgG, or normal culture media, the fibroblasts were washed PCR, immunoblotting, and immunohistochemistry assays of cer- with PBS and fixed with 100% methanol at 4°C for 2 min. The fibroblasts tain ECM components known to play important roles in the pro- were washed with PBS again and incubated with p-Smad3 polyclonal Abs. fibrotic phenotype of the SSc fibroblast. After washing, the fibroblasts were incubated with anti-rabbit Ab conju- gated with FITC and washed with PBS. 4Ј,6Ј-Diamidino-2-phenylinodole was used for nuclear counterstaining. The images of fibroblasts with flu- Materials and Methods orescence-labeled proteins were acquired with a digital camera of the flu- Recombinant fibrillin-1 Ag and anti-fibrillin-1 autoantibodies orescence microscopy (Nikon). Our previous studies indicated that some autoantibodies to fibrillin-1 in Western blot analysis SSc sera, but not all, are directed against a 30-kDa glutathione fusion Cellular lysates from cultured fibroblasts were obtained using PBS-TDS protein containing the proline-rich C region of human fibrillin-1 (11, 12). (0.1% Triton X-100, 12.1 mM sodium deoxycholate, 3.5 mM SDS in PBS, The recombinant peptide (aa 378–495) in this study was cloned by RT- pH 7.4) containing a mixture
Load more

Recommended publications
  • Understanding and Managing Scleroderma
    Understanding and Managing Scleroderma A publication of Scleroderma Foundation 300 Rosewood Drive, Suite 105 Danvers, MA 01923 Maureen D. Mayes, M.D., M.P.H. Understanding and Understanding My notes and Managing Scleroderma Managing Scleroderma This booklet is intended to help people with scleroderma, their families and others interested ________________________ in learning more about the disease to better understand what scleroderma is, what effects ________________________ it may have, and what those with scleroderma can do to help themselves and their physicians ________________________ manage the disease. It answers some of the most frequently asked questions about ________________________ A publication of Maureen D. Mayes, M.D., M.P.H. Scleroderma Foundation 300 Rosewood Drive, Suite 105 scleroderma. Danvers, MA 01923 800-722-HOPE (4673) www.scleroderma.org www.facebook.com/sclerodermaUS www.twitter.com/scleroderma ________________________ Disclaimer The Scleroderma Foundation does not provide medical advice nor does it ________________________ endorse any drug or treatment mentioned herein. ________________________ The material contained in this booklet is presented for general information only. It is not intended to provide medical advice, to answer questions specific to the condition or problems of particular individuals, nor in ________________________ any way to substitute for the professional advice and care of qualified physicians. Mention of particular drugs and/or treatments is for ________________________ information purposes only and does not constitute an endorsement of said drugs and/or treatments. ________________________ Thanks! ________________________ The Scleroderma Foundation expresses its deep appreciation to the many ________________________ physicians whose efforts have led to this booklet. Special thanks are owed to Maureen D. Mayes, M.D., M.P.H., of the ________________________ University of Texas McGovern Medical School, Houston.
    [Show full text]
  • The Voice of the Patient
    The Voice of the Patient A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative Systemic Sclerosis Public Meeting: October 13, 2020 Report Date: June 30, 2021 Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA) 1 Table of Contents Introduction ............................................................................................................................ 3 Overview of Systemic Sclerosis ................................................................................................................. 3 Meeting Overview ..................................................................................................................................... 3 Report Overview and Key Themes ............................................................................................................ 5 Topic 1: Disease Symptoms and Daily Impacts That Matter Most to Patients .......................... 6 Perspectives on Most Significant Symptoms ............................................................................................ 6 Overall Impact of Systemic Sclerosis on Daily Life .................................................................................... 9 Topic 2: Patient Perspectives on Treatments for Systemic Sclerosis ....................................... 11 Perspectives on Current Treatments ...................................................................................................... 11 Perspectives on Ideal
    [Show full text]
  • The Articular Manifestations of Progressive Systemic Sclerosis (Scleroderma) MURRAY BARON, PETER LEE, and EDWARD C
    Ann Rheum Dis: first published as 10.1136/ard.41.2.147 on 1 April 1982. Downloaded from Annals ofthe Rheumatic Diseases, 1982, 41, 147-152 The articular manifestations of progressive systemic sclerosis (scleroderma) MURRAY BARON, PETER LEE, AND EDWARD C. KEYSTONE From the University of Toronto Rheumatic Disease Unit, The Wellesley Hospital, 160 Wellesley Street East, Toronto, Ontario, Canada M4Y 1J3 SUMMARY The articular manifestations of progressive systemic sclerosis (PSS) were studied in 38 patients. Of these, 66 % experienced joint pain and 61 % had signs of joint inflammation. Limita- tion of joint movement was seen in 45 %. Radiological abnormalities included periarticular osteoporosis (42 %), joint space narrowing (34%), and erosions (40%). Erosive disease did not correlate with disease duration, presence of rheumatoid factor, antinuclear antibodies, distal tuft resorption, or the extent of the scleroderma skin changes. Calcinosis was seen more frequently in those patients with articular erosions (67 %). Erosive osteoarthritis of the distal interphalangeal joints (7 patients) was associated with impaired finger flexion. Joint involvement in PSS occurs frequently and may resemble rheumatoid arthritis in the early stages but is less destructive. The occurrence of unrelated arthropathy, such as primary osteoarthritis, is not uncommon, and its differentiation from true PSS joint disease can be difficult. Articular manifestations are common in progressive spective study and fulfilling the preliminary diagnos- systemic sclerosis (scleroderma, PSS), and joint pain tic criteria for PSS1 were evaluated by one author is a frequent presenting feature of this disease.' Joint (M.B.). A history of joint manifestations was symptoms have been noted in 12 to 66% of patients obtained in each case according to a standard pro- http://ard.bmj.com/ at the time of diagnosis2`6 and in 24 to 97% of tocol.
    [Show full text]
  • Systemic Scleroderma
    Systemic scleroderma Description Systemic scleroderma is an autoimmune disorder that affects the skin and internal organs. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. The word "scleroderma" means hard skin in Greek, and the condition is characterized by the buildup of scar tissue (fibrosis) in the skin and other organs. The condition is also called systemic sclerosis because the fibrosis can affect organs other than the skin. Fibrosis is due to the excess production of a tough protein called collagen, which normally strengthens and supports connective tissues throughout the body. The signs and symptoms of systemic scleroderma usually begin with episodes of Raynaud phenomenon, which can occur weeks to years before fibrosis. In Raynaud phenomenon, the fingers and toes of affected individuals turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities. Another early sign of systemic scleroderma is puffy or swollen hands before thickening and hardening of the skin due to fibrosis. Skin thickening usually occurs first in the fingers (called sclerodactyly) and may also involve the hands and face. In addition, people with systemic scleroderma often have open sores (ulcers) on their fingers, painful bumps under the skin (calcinosis) , or small clusters of enlarged blood vessels just under the skin (telangiectasia). Fibrosis can also affect internal organs and can lead to impairment or failure of the affected organs. The most commonly affected organs are the esophagus, heart, lungs, and kidneys. Internal organ involvement may be signaled by heartburn, difficulty swallowing (dysphagia), high blood pressure (hypertension), kidney problems, shortness of breath, diarrhea, or impairment of the muscle contractions that move food through the digestive tract (intestinal pseudo-obstruction).
    [Show full text]
  • Hepatic Manifestations of Autoimmune Rheumatic Diseases ANNALS of GASTROENTEROLOGY 2005, 18(3):309-324309
    Hepatic manifestations of autoimmune rheumatic diseases ANNALS OF GASTROENTEROLOGY 2005, 18(3):309-324309 Review Hepatic manifestations of autoimmune rheumatic diseases Aspasia Soultati, S. Dourakis SUMMARY the association between primary autoimmune rheumatolog- ic disease and associated hepatic abnormalities and the Autoimmune rheumatic diseases including Systemic Lu- pharmaceutical interventions that are related to liver dam- pus Erythematosus, Rheumatoid Arthritis, Sjogrens syn- age are presented. drome, Myositis, Antiphospholipid Syndrome, Behcets syndrome, Scleroderma and Vasculitides have been associ- Key words: Connective Tissue Disease, Systemic Lupus Ery- ated with hepatic injury by virtue of multisystem immune thematosus, Rheumatoid Arthritis, Sjogrens syndrome, and inflammatory involvement. Liver involvement preva- Myositis, Giant-Cell Arteritis, Antiphospholipid Syndrome, lence, significance and specific hepatic pathology vary. Af- Behcets syndrome, Scleroderma, Vasculitis, Steatosis, Nod- ter careful exclusion of potentially hepatotoxic drugs or co- ular Regenerative Hyperplasia, portal hypertension, Autoim- incident viral hepatitis the question remains whether liver mune Hepatitis, Primary Biliary Cirrhosis, Primary Scleros- involvement emerges as a manifestation of generalized con- ing Cholangitis nective tissue disease or it reflects an underlying primary liver disease sharing an immunological mechanism. Com- 1. Introduction monly recognised features include mild elevation of liver A variety of autoimmune rheumatic diseases
    [Show full text]
  • Humanistic and Cost Burden of Systemic Sclerosis: a Review of the Literature
    Autoimmunity Reviews 16 (2017) 1147–1154 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev Review Humanistic and cost burden of systemic sclerosis: A review of the literature Aryeh Fischer a, Evelina Zimovetz b, Caroline Ling b, Dirk Esser c, Nils Schoof c,⁎ a University of Colorado School of Medicine, Denver, CO, USA b RTI Health Solutions, Manchester, United Kingdom c Boehringer Ingelheim GmbH, Ingelheim, Germany article info abstract Article history: Background: Systemic sclerosis (SSc), or systemic scleroderma, is a chronic multisystem autoimmune disease Received 12 August 2017 characterised by widespread vascular injury and progressive fibrosis of the skin and internal organs. Patients with Accepted 17 August 2017 SSc have decreased survival, with pulmonary involvement as the main cause of death. Current treatments for SSc Available online 9 September 2017 manage a range of symptoms but not the cause of the disease. Our review describes the humanistic and cost burden of SSc. Keywords: Methods: A structured review of the literature was conducted, using predefined search strategies to search PubMed, Systemic sclerosis Embase, and the Cochrane Library. Grey literature searches also were conducted. Scleroderma fi Quality of life Results: In total, 2226 articles were identi ed in the databases and 52 were included; an additional 10 sources were QOL included from the grey literature. The review identified six studies reporting relevant cost estimates conducted in Cost of illness five different countries and four studies that assessed the humanistic burden of SSc. Total direct annual medical costs per patient for Europe varied from €3544 to €8452. For Canada, these costs were reported to be from Can$5038 to Can$10,673.
    [Show full text]
  • Vol 120 No 1254 ISSN 1175 8716
    THE NEW ZEALAND MEDICAL JOURNAL Vol 120 No 1254 ISSN 1175 8716 CONTENTS This Issue in the Journal A summary of the original articles featured in this issue Editorials Hip fracture management in New Zealand—we need to do better Geoffrey Horne Fees in primary care James Reid Fees reviews of New Zealand general practices—a New Zealand Medical Association (NZMA) perspective Peter Foley Original Articles Older patients with hip fractures: evaluation of a long-term specialist orthopaedic medicine service in their outcomes John Thwaites, Fazal Mann, Nigel Gilchrist, John McKie, Richard Sainsbury Management of scleroderma in a New Zealand tertiary rheumatology centre: emphasis on pulmonary complications Kristine Ng, Peter Gow Exploring general practitioner identification and management of psychosocial Yellow Flags in acute low back pain Cameron Crawford, Kathleen Ryan, Edward Shipton Practitioners, patients, and their visits: a description of accident and medical (A&M) clinics in New Zealand, 2001/2 Phil Hider, Roy Lay-Yee, Peter Davis Case Reports Rat-bite fever: a cautionary tale Renukadas Sakalkale, Chris Mansell, Deborah Whalley, Kim Wisnewski-Smith, David Harte, Paul Reeve Brainstem lesions presenting with nausea and vomiting Ian Rosemergy, Stuart Mossman Viewpoint Folic acid and neural tube defects in New Zealand: a cautionary tale? Joanne Dixon NZMJ 18 May 2007, Vol 120 No 1254 Page 1 of 86 URL: http://www.nzma.org.nz/journal/120-1254/2552/ © NZMA 100 Years Ago in the NZMJ A case of cerebellar haemorrhage Medical Image Arthritis and macroglossia
    [Show full text]
  • Systemic Sclerosis/Scleroderma: a Treatable Multisystem Disease
    Systemic Sclerosis/Scleroderma: A Treatable Multisystem Disease MONIQUE HINCHCLIFF, MD, and JOHN VARGA, MD Northwestern University, Feinberg School of Medicine, Chicago, Illinois Systemic sclerosis (systemic scleroderma) is a chronic connective tissue disease of unknown etiology that causes wide- spread microvascular damage and excessive deposition of collagen in the skin and internal organs. Raynaud phenome- non and scleroderma (hardening of the skin) are hallmarks of the disease. The typical patient is a young or middle-age woman with a history of Raynaud phenomenon who presents with skin induration and internal organ dysfunction. Clinical evaluation and laboratory testing, along with pulmonary function testing, Doppler echocardiography, and high-resolution computed tomography of the chest, establish the diagnosis and detect visceral involvement. Patients with systemic sclerosis can be classified into two distinct clinical subsets with different patterns of skin and internal organ involvement, autoantibody production, and survival. Prognosis is determined by the degree of internal organ involvement. Although no disease-modifying therapy has been proven effective, complications of systemic sclerosis are treatable, and interventions for organ-specific manifestations have improved substantially. Medications (e.g., cal- cium channel blockers and angiotensin-II receptor blockers for Raynaud phenomenon, appropriate treatments for gastroesophageal reflux disease) and lifestyle modifications can help prevent complications, such as digital ulcers and Barrett esophagus. Endothelin-1 receptor blockers and phosphodiesterase-5 inhibitors improve pulmonary arte- rial hypertension. The risk of renal damage from scleroderma renal crisis can be lessened by early detection, prompt initiation of angiotensin-converting enzyme inhibitor therapy, and avoidance of high-dose corticosteroids. Optimal patient care includes an integrated, multidisciplinary approach to promptly and effectively recognize, evaluate, and manage complications and limit end-organ dysfunction.
    [Show full text]
  • Nutritional Implications of GI-Related Scleroderma
    NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #148 Carol Rees Parrish, M.S., R.D., Series Editor Nutritional Implications of GI-Related Scleroderma Soumya Chatterjee Scleroderma (SSc) is an autoimmune disease characterized by progressive fibrosis of skin and various internal organs, including the lungs, heart, kidneys, and the gastrointestinal (GI) tract. Second only to skin disease, GI tract involvement is the next most common manifestation of SSc. Any part of the GI tract may be affected, leading to considerable impairment of quality of life. When GI involvement is extensive, severe malnutrition can occur and it can even result in death in about 20% of patients. Early recognition and management may alter the long-term outcome. Effective collaboration with gastroenterologists in the evaluation and management of SSc in a multispecialty partnership model has the potential to produce better outcomes and improve survival in these patients. This article discusses the nutritional implications and current evidence-based management recommendations for the wide range of GI manifestations in SSc. INTRODUCTION cleroderma, or systemic sclerosis (SSc), is originally coined (Gr., ‘skleros’ = thickening, ‘dermos’ an autoimmune disease of unclear etiology, = skin). There are two main subtypes of SSc, based on Scharacterized by progressive fibrosis of skin the extent of skin hardening: and various internal organs, an ongoing occlusive • limited SSc (lcSSc, formerly CREST syndrome) microvasculopathy, and abnormalities of the immune only involving the distal extremities (beyond system. There is wide variability in the prevalence of elbows and knees) and face. SSc worldwide. In the United States, about 250 cases per million Americans are afflicted with this disease. • diffuse SSc (dcSSc), where skin tightening is Progressive skin thickening is an integral part of the widespread, including the trunk and proximal disease, explaining how the term ‘scleroderma’ was extremities.
    [Show full text]
  • Current Management of the Gastrointestinal Complications of Systemic Sclerosis
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UCL Discovery Current management of the gastrointestinal complications of systemic sclerosis Anton Emmanuel Gastrointestinal Physiology Unit, University College Hospital, 235 Euston Road, London NW1 2BU, UK. [email protected] Abstract Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in over 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum being most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an improved understanding of the intestinal pathophysiology of systemic sclerosis. This Review will describe the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation. Key points Gut involvement in systemic sclerosis
    [Show full text]
  • Clinical Aspects of Overlap Syndrome - Case Report and Literature Review
    Arch Clin Biomed Res 2018; 2 (4): 117-131 DOI: 10.26502/acbr.5017051 Case Report Clinical Aspects of Overlap Syndrome - Case Report and Literature Review Bogna Grygiel-Górniak*, Oscar Nicholas Godtfredsen, Gunnar Nyborg Eid, Nicholas Werczak, Mariusz Puszczewicz Department of Rheumatology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland *Corresponding Author: Bogna Grygiel-Górniak, Department of Rheumatology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland, E-mail: [email protected] Received: 04 May 2018; Accepted: 08 May 2018; Published: 10 May 2018 Abstract We report a patient with overlap syndrome (systemic sclerosis (SSc) and polymyositis (PM)). The heterogeneous nature of systemic sclerosis may lead to a great diversity in the clinical presentation of the disease. With this case report we aim to demonstrate clinical manifestations of systemic sclerosis and polymyositis in an overlap-syndrome, with support from antibody profile and laboratory data. Keywords: Overlap syndrome; Systemic sclerosis; Polymyositis; Pulmonary fibrosis; Treatment 1. Case Report A 51-year old female patient came to the Pulmonology Ward in 2015 complaining of shortness of breath and reduced exercise tolerance for approximately 1 year. Clinical examination revealed a rash on the neck that spread throughout the upper part of thorax, in addition to swollen, reddish fingers with skin stiffness on the hands. The patient also suffered from a swollen face and swollen eyelids. On auscultation, crackles were heard in the lower lung fields. On X-ray, changes in the interstitium were seen, and computer tomography confirmed fibrotic areas located peripherally in the lower lobes. In HRCT (high definition computer tomography) fibrosis was found in both lungs peripherally in the lower posterior lobes.
    [Show full text]
  • Systemic Sclerosis Presenting As CREST Syndrome: a Case Report and Review
    JOURNAL OF ERITREAN MEDICAL ASSOCIATION JEMA Systemic sclerosis presenting as CREST syndrome: A case report and review Amanuel Habtemichael1, Asmerom Tesfamariam1, Daniel Tekie1, Wienishet, MD2 Institutional affiliation: 1 Orotta School of Medicine 2 Orotta National Medical Surgical Referral Hospital Corresponding author: Amanuel Habtemichael Orotta School of Medicine P.O.Box 10549, Asmara, Eritrea : Email: [email protected] Abstract Systemic sclerosis (SSc) is a chronic multisystem disorder of unknown etiology, characterized by diffuse fibrosis; degenerative changes; and vascular abnormalities in the skin (scleroderma), articular structures, and internal organs especially the esophagus, GI tract, lung, heart, and kidney. We report the case of a 31 years old female patient who came to the ED with complications of SSc after has been diagnosed with a limited cutaneous scleroderma. This case illustrates the varied multisystem presentation of SSc. Introduction revealed enlargement of right atrium and ventricle, and tricuspid regurgitation without valvular fibrosis. Systemic sclerosis (systemic scleroderma) is a Along with full investigations and management diagnose chronic connective tissue disease of unknown etiology was established as limited cutaneous scleroderma with that causes widespread microvascular damage and RHF secondary to pulmonary arterial hypertension. She excessive deposition of collagen in the skin and was discharged home with lasix 40 mg PO daily, digoxin internal organs. 1 The degree and rate of skin and 0.125 mg PO daily and prendisolone 5 mg in tapering dose. internal organ involvement vary among patients. SSc She had been following at the dermatology, cardiac and has a worldwide distribution and affects all races. The infectious clinics of the hospital with the periodically given prevalence of scleroderma is estimated to be between medications.
    [Show full text]