Harrisons rheumatology 2010

Second Edition HARRISON’S Rheumatology Derived from Harrison’s Principles of Internal Medicine, 17th Edition Editors ANTHONY S FAUCI, MD Chief, Laboratory of Immunoregulation; Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda DENNIS L KASPER, MD William Ellery Channing Professor of Medicine, Professor of Microbiology and Molecular Genetics, Harvard Medical School; Director, Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston DAN L LONGO, MD Scientific Director, National Institute on Aging, National Institutes of Health, Bethesda and Baltimore EUGENE BRAUNWALD, MD Distinguished Hersey Professor of Medicine, Harvard Medical School; Chairman,TIMI Study Group, Brigham and Women’s Hospital, Boston STEPHEN L HAUSER, MD Robert A Fishman Distinguished Professor and Chairman, Department of Neurology, University of California, San Francisco J LARRY JAMESON, MD, PhD Professor of Medicine;Vice President for Medical Affairs and Lewis Landsberg Dean, Northwestern University Feinberg School of Medicine, Chicago JOSEPH LOSCALZO, MD, PhD Hersey Professor of Theory and Practice of Medicine, Harvard Medical School; Chairman, Department of Medicine; Physician-in-Chief, Brigham and Women’s Hospital, Boston Second Edition HARRISON’S Rheumatology Editor Anthony S Fauci, MD Chief, Laboratory of Immunoregulation; Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda Associate Editor Carol A Langford, MD, MHS Associate Professor of Medicine; Director, Center for Vasculitis Care and Research, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto Copyright © 2010 by The McGraw-Hill Companies, Inc All rights reserved Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher ISBN: 978-0-07-174146-0 MHID: 0-07-174146-1 The material in this eBook also appears in the print version of this title: ISBN: 978-0-07-174143-9, MHID: 0-07-174143-7 All trademarks are trademarks of their respective owners Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark Where such designations appear in this book, they have been printed with initial caps McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs To contact a representative please e-mail us at bulksales@mcgraw-hill.com TERMS OF USE This is a copyrighted work and The McGraw-Hill Companies, Inc (“McGrawHill”) and its licensors reserve all rights in and to the work Use of this work is subject to these terms Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill’s prior consent You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited Your right to use the work may be terminated if you fail to comply with these terms THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE McGraw-Hill and its licensors not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom McGraw-Hill has no responsibility for the content of any information accessed through the work Under no circumstances shall McGraw-Hill and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise CONTENTS Contributors vii 14 Familial Mediterranean Fever 184 Daniel L Kastner Preface ix 15 Amyloidosis 189 David C Seldin, Martha Skinner SECTION I 16 Polymyositis, Dermatomyositis, and Inclusion Body Myositis 197 Marinos C Dalakas THE IMMUNE SYSTEM IN HEALTH AND DISEASE Introduction to the Immune System Barton F Haynes, Kelly A Soderberg,Anthony S Fauci SECTION III The Major Histocompatibility Complex 44 Gerald T Nepom DISORDERS OF THE JOINTS AND ADJACENT TISSUES Autoimmunity and Autoimmune Diseases 57 Peter E Lipsky, Betty Diamond 17 Approach to Articular and Musculoskeletal Disorders 210 John J Cush, Peter E Lipsky SECTION II 18 Osteoarthritis 223 David T Felson DISORDERS OF IMMUNE-MEDIATED INJURY Systemic Lupus Erythematosus 66 Bevra Hannahs Hahn 19 Gout and Other Crystal-Associated Arthropathies 235 H Ralph Schumacher, Lan X Chen Rheumatoid Arthritis 82 Peter E Lipsky 20 Infectious Arthritis 243 Lawrence C Madoff Acute Rheumatic Fever 100 Jonathan R Carapetis 21 Fibromyalgia 254 Carol A Langford, Bruce C Gilliland Systemic Sclerosis (Scleroderma) and Related Disorders 107 John Varga 22 Arthritis Associated with Systemic Disease and Other Arthritides 259 Carol A Langford, Bruce C Gilliland Sjögren’s Syndrome 124 Haralampos M Moutsopoulos 23 Periarticular Disorders of the Extremities 271 Carol A Langford, Bruce C Gilliland The Spondyloarthritides 129 Joel D.Taurog Appendix Laboratory Values of Clinical Importance 277 Alexander Kratz, Michael A Pesce, Daniel J Fink 10 The Vasculitis Syndromes 144 Carol A Langford,Anthony S Fauci Review and Self-Assessment 299 Charles Wiener, Gerald Bloomfield, Cynthia D Brown, Joshua Schiffer, Adam Spivak 11 Behçet’s Syndrome 166 Haralampos M Moutsopoulos Index 327 12 Relapsing Polychondritis 168 Carol A Langford, Bruce C Gilliland 13 Sarcoidosis 173 Robert P Baughman, Elyse E Lower v This page intentionally left blank CONTRIBUTORS Numbers in brackets refer to the chapter(s) written or co-written by the contributor DANIEL KASTNER, MD, PhD Chief, Genetics and Genomic Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda [14] ROBERT P BAUGHMAN, MD Professor of Medicine, Cincinnati [13] GERALD BLOOMFIELD, MD, MPH Department of Internal Medicine,The Johns Hopkins University School of Medicine, Baltimore [Review and Self-Assessment] ALEXANDER KRATZ, MD, PhD, MPH Assistant Professor of Clinical Pathology, Columbia University College of Physicians and Surgeons;Associate Director, Core Laboratory, Columbia University Medical Center, New YorkPresbyterian Hospital; Director,Allen Pavilion Laboratory, New York [Appendix] CYNTHIA D BROWN, MD Department of Internal Medicine,The Johns Hopkins University School of Medicine, Baltimore [Review and Self-Assessment] JONATHAN R CARAPETIS, MBBS, PhD Director, Menzies School of Health Research; Professor, Charles Darwin University,Australia [6] CAROL A LANGFORD, MD, MHS Associate Professor of Medicine; Director, Center for Vasculitis Care and Research, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland [10, 12, 21, 22, 23] LAN X CHEN, MD Clinical Assistant Professor of Medicine, University of Pennsylvania, Penn Presbyterian Medical Center and Philadelphia Veteran Affairs Medical Center, Philadelphia [19] PETER E LIPSKY, MD Chief,Autoimmunity Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda [3, 5, 17] JOHN J CUSH, MD Director of Clinical Rheumatology, Baylor Research Institute; Professor of Medicine and Rheumatology, Baylor University Medical Center, Dallas [17] ELYSE E LOWER, MD Professor of Medicine, University of Cincinnati, Cincinnati [13] MARINOS C DALAKAS, MD Professor of Neurology; Chief, Neuromuscular Diseases Section, NINDS, National Institute of Health, Bethesda [16] LAWRENCE C MADOFF, MD Associate Professor of Medicine, Harvard Medical School, Boston [20] HARALAMPOS M MOUTSOPOULOS, MD Professor and Chair, Department of Pathophysiology, School of Medicine, National University of Athens, Greece [8, 11] BETTY DIAMOND, MD Chief,Autoimmune Disease Center,The Feinstein Institute for Medical Research, New York [3] GERALD T NEPOM, MD, PhD Director, Benaroya Research Institute at Virginia Mason; Professor, University of Washington School of Medicine, Seattle [2] ANTHONY S FAUCI, MD, DSC (Hon), DM&S (Hon), DHL (Hon), DPS (Hon), DLM (Hon), DMS (Hon) Chief, Laboratory of Immunoregulation; Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda [1, 10] MICHAEL A PESCE, PhD Clinical Professor of Pathology, Columbia University College of Physicians and Surgeons; Director of Specialty Laboratory, New York Presbyterian Hospital, Columbia University Medical Center, New York [Appendix] DAVID T FELSON, MD, MPH Professor of Medicine and Epidemiology; Chief, Clinical Epidemiology Unit, Boston University, Boston [18] DANIEL J FINK,† MD, MPH Associate Professor of Clinical Pathology, College of Physicians and Surgeons, Columbia University, New York [Appendix] JOSHUA SCHIFFER, MD Department of Internal Medicine,The Johns Hopkins University School of Medicine, Baltimore [Review and Self-Assessment] BRUCE C GILLILAND,† MD Professor of Medicine and Laboratory Medicine, University of Washington School of Medicine, Seattle [12, 21, 22, 23] H RALPH SCHUMACHER, MD Professor of Medicine, University of Pennsylvania School of Medicine, Philadelphia [19] BEVRA HANNAHS HAHN, MD Professor of Medicine; Chief of Rheumatology;Vice Chair, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles [4] DAVID C SELDIN, MD, PhD Professor of Medicine and Microbiology; Director,Amyloid Treatment and Research Program Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston [15] BARTON F HAYNES, MD Frederic M Hanes Professor of Medicine and Immunology, Departments of Medicine and Immunology; Director, Duke Human Vaccine Institute, Duke University School of Medicine, Durham [1] MARTHA SKINNER, MD Professor of Medicine, Boston University School of Medicine; Director, Special Projects,Amyloid Treatment and Research Program, Boston [15] † Deceased vii viii Contributors KELLY A SODERBERG, PhD, MPH Director, Program Management, Duke Human Vaccine Institute, Duke University School of Medicine, Durham [1] JOHN VARGA, MD Hughes Professor of Medicine, Northwestern University Feinberg School of Medicine, Chicago [7] ADAM SPIVAK, MD Department of Internal Medicine,The Johns Hopkins University School of Medicine, Baltimore [Review and Self-Assessment] CHARLES WIENER, MD Professor of Medicine and Physiology; Vice Chair, Department of Medicine; Director, Osler Medical Training Program, The Johns Hopkins University School of Medicine, Baltimore [Review and Self-Assessment] JOEL D TAUROG, MD Professor of Internal Medicine,William M and Gatha Burnett Professor for Arthritis Research, University of Texas Southwestern Medical Center, Dallas [9] PREFACE In 2006, the first Harrison’s Rheumatology sectional was introduced with the goal of expanding the outreach of medical knowledge that began with the first edition of Harrison’s Principles of Internal Medicine, which was published over 60 years ago The sectional, which is comprised of the immunology and rheumatology chapters contained in Harrison’s Principles of Internal Medicine, sought to provide readers with a current view of the science and practice of rheumatology After its introduction, we were gratified to learn that this sectional was being utilized not only by young physicians gaining their first exposure to rheumatology, but also by a diversity of health care professionals seeking to remain updated on the latest advancements within this dynamic subspecialty of internal medicine With this edition of the Harrison’s Rheumatology, it remains our goal to provide the expertise of leaders in rheumatology and immunology to all students of medicine who wish to learn more about this important and constantly changing field The aspects of medical care encompassed by rheumatology greatly impact human health Musculoskeletal symptoms are among the leading reasons that patients seek medical attention, and it is now estimated that one out of three people will be affected by arthritis Joint and muscle pain not only affect quality of life and produce disability, they may also be heralding symptoms of serious inflammatory, infectious, or neoplastic diseases Because of their frequency and the morbidity associated with the disease itself, as well as the therapeutic modalities employed, rheumatic diseases impact all physicians Although the connective tissues form the foundation of rheumatology, this specialty encompasses a wide spectrum of medical disorders which exemplify the diversity and complexity of internal medicine Rheumatic diseases can range from processes characterized by monarticular arthropathy to multisystem illnesses that carry a significant risk of morbidity or mortality The effective practice of rheumatology therefore requires broad-based diagnostic skills, a strong fundamental understanding of internal medicine, the ability to recognize life-threatening disease, and the knowledge of how to utilize and monitor a wide range of treatments in which benefit must be balanced against risk Understanding these challenges provides an opportunity to improve the lives of patients, and it is these factors that make the practice of rheumatology an immensely rewarding area of internal medicine Another facet of rheumatology that has captivated the interest of both clinicians and biomedical researchers is its relationship to immunology and autoimmunity From early studies in rheumatology, clinical and histologic evidence of inflammation supported the view that the immune system mediated many forms of joint and tissue injury Laboratory-based investigations have not only provided firm evidence for the immunologic basis of these diseases, but they have identified specific mechanisms involved in the pathogenesis of individual clinical entities Recognition of the pathways involved in disease and the potential to target specific immune effector functions have revolutionized the treatment of many rheumatic diseases Such investigations will continue to shed insights regarding the pathogenesis of a wide range of rheumatic diseases, and will bring forth novel therapies that offer even greater potential to lessen pain, reduce joint and organ damage, and improve overall clinical outcome This sectional was originally developed in recognition of the importance of rheumatology to the practice of internal medicine as well as the rapid pace of scientific growth in this specialty This assessment has been borne out by the numerous advancements in rheumatology that have been made even within the short period of time since the last sectional was published The need for this sectional is a tribute to the hard work of many dedicated individuals at both the bench and the bedside whose contributions have greatly benefited our patients It is the continued hope of the editors that this sectional will not only increase knowledge of the rheumatic diseases, but also serve to heighten appreciation for this fascinating specialty Anthony S Fauci, MD Carol A Langford, MD, MHS ix 336 Henoch-Schönlein purpura, 158 clinical manifestations of, 159 definition of, 158 incidence of, 158 laboratory manifestations of, 159 pathogenesis of, 158–159 pathology of, 158–159 prevalence of, 158 renal involvement in, 159 treatment for, 159 Hepatitis B, 50 PAN and, 312, 319–320 Hepatitis B antigenemia, 153 Hepatitis C, 145 essential mixed cryoglobulinemia and, 160–161 Hepatocytes, 11t Hepatomegaly, 193 Hereditary hemorrhagic telangiectasia, 115 Hereditary inclusion body myopathy (h-IBM), 199 Hereditary periodic fever, 35 syndromes of, 185t Hereditary recurrent fevers, 187 Heterodimer, 50 HEVs See High endothelial venules h-IBM See Hereditary inclusion body myopathy Hidradenitis suppurativa, 142 HIDS See Hyperimmunoglobulin D with periodic fever syndrome High endothelial venules (HEVs), 37 abnormal induction of, 38 High-density lipoprotein cholesterol classification, 290t High-resolution computed tomography (HRCT) for ILD, 116 of lungs, 116f Hip pain, 218, 218f exercise and, 230–231 OA and, 226 surgery for, 233 x-rays for, 230 Histamine release, 20 Histoplasma capsulatum, 249f HIV infection acute, 315 arthritis syndromes and, 249 PsA and, 140 psoriasis and, 138 sarcoidosis and, 174 Sjögren’s syndrome and, 127t vasculitis and, 163 Index HLA, 44 disease susceptibility and, 52, 59–60 molecular mechanisms of, 56 heavy chain of, 44 light chain of, 44 RA and, 55 transplantation role of, 52 HLA class I genes, 44–45 HLA class I receptors, 50 HLA class II genes, 45 HLA class II region, 46 HLA class III region, 47 HLA region, 45f HLA serotype, 54 HLA-B alleles, 50 HLA-β1 alleles, 83 HLA-B27, 129 HLA-D complex, 83 HLA-DR4, 82, 168 HLA-F function, 46 HLA-mismatched bone marrow, 109 HOA See Hypertrophic osteoarthropathy Hookworm arthritis, 250 Host defense, phases of, 36 Housemaid’s knee, 272 HRCT See High-resolution computed tomography Human cytomegalovirus (hCMV), 108 Human immunoglobulins See Immunoglobulin Human leukocyte antigen See HLA Human leukocyte surface antigens See CD classification of human lymphocyte differentiation antigens Human T cells, 23 Humoral autoimmunity, 110 Humoral cellular proteins, 6t Humoral immunity, 40 deficiencies of, 245 DM and, 200 Hyaline cartilage, 168 Hyaluronic acid, 233 Hydralazine, 162 Hydrochlorothiazide, 80 Hydroxyapatite deposition, 272 Hydroxychloroquine, 74t for sarcoidosis, 182t, 183 Hypercalcemia, 178 Hypercholesterolemia, 263 Hypereosinophilic syndromes, 20 Hypergammaglobulinemia, 149 Hyperimmunoglobulin D with periodic fever syndrome (HIDS), 185t, 187 Hyperkeratosis See Dystrophic hyperkeratosis Hyperlipidemia joint involvement in, 263 musculoskeletal disorders associated with, 263 Hyperlipoprotinemia, 263 Hypermutation, 28 Hyperoxalemia, 240 Hyperplasia, of synovial lining cells, 83 Hyperpyrexia, in FMF, 184 Hypersensitivity vasculitis, 159 Hypersplenism, 89, 323 Hypertension See also Malignant hypertension with PAN, 154 SSc and, 117 Hyperthyroidism, 53t Hypertrophic osteoarthropathy (HOA), 265 clinical manifestations of, 266–267 with clubbing, 265 definition of, 265 development of, 266 disorders associated with, 267t humoral theory of, 266 joint paint with, 267 laboratory findings of, 267 megakaryocytes in, 266 neurogenic theory of, 266 pathogenesis of, 265–266 pathology of, 265–266 pathophysiology of, 265–266 presentation of, 265 primary, 266 secondary, 266 treatment for, 267–268 Hypertrophy, of synovial lining cells, 83 Hyperuricemia, 219, 237–238, 314 Hypervariable regions, 28 Hypoalbuminemia, 191 Hypoaldosteronism, 313 Hypoperfusion, endofascicular, 201 Hypothyroidism, fibromyalgia and, 257 Hypouricemic therapy, for gout, 237–238 IBD See Inflammatory bowel disease IBM See Inclusion body myositis ICAM-1, 110 See Intercellular adhesion molecule ICOS See Inducible co-stimulator Idiopathic cutaneous vasculitis, 159 clinical manifestations of, 159–160 definition of, 159 Index Idiopathic cutaneous vasculitis (Cont.): diagnosis of, 160 incidence of, 159 laboratory manifestations of, 159–160 pathogenesis of, 159 pathology of, 159 prevalence of, 159 treatment of, 160 Idiopathic polymyositis, 118 Idiotype, 28 IFN-γ, 85, 86 IFNs See Interferons Ig See Immunoglobulin Ig gene rearrangement, 27 random, 28 Ig LC deposit, 191 IgA nephropathy, 21 IgA secretion, 29, 33 IgD, 29, 31 IgE, 29–30 IgG, 29 IgG antibodies, 70 IgM, 31 IgM antibodies, 29 IgM rheumatoid factors, 89 IL See Interleukin IL-1 role of, 85 secretion of, 146 synthesis of, 225 IL-1 receptor antagonist, 94 ILD See Interstitial lung disease Iliopsoas bursitis, 218, 271 IM benzathine penicillin G Erythromycin, 103–104 Immediate-type hypersensitivity, 38 See also Allergic diseases Immune cells, migration of, 37f Immune function, clinical evaluation of, 40 Immune memory, Immune reconstitution, 41t Immune responses ARF and, 101 regulation of, 30 Immune system, See also Adaptive immune system; Innate immune system endogenous derangements of, 58 features of, 57 molecule defects, 34t Immune tolerance, 31 Immune-complex formation, 38 diseases of, 144–145 tissue damage mechanisms in, 145 Immune-complex syndromes, 40t Immune-mediated damage to microbes, mechanisms of, 35 Immune-mediated disease, 56 Immune-mediated infertility, 62t Immunity, at mucosal surfaces, 31 Immunocompetent cells distribution of, 22 proportion of, 22 Immunogenetics, inflammatory myopathies and, 200 Immunogenic peptides, 48 Immunoglobulin (Ig), 28 See also Serum immunoglobulin characteristics of, 28 clinical chemistry of, 284t deficiencies in, 42 domains of, 28 intravenous, 41t properties of, 29t rearrangement of, 23f in relapsing polychondritis, 169 structure of, 28 superfamily, 21 Immunoglobulin gene superfamily, 24 Immunologic memory, 22 Immunologic priming, 22 Immunologic privilege, 58 Immunologic synapses, 26 Immunology, 280t–286t Immunomodulation, for inflammatory myopathies, 207 Immunomodulatory agents, development of, 41t Immunoreceptor tyrosine-based activation (ITAM), 25f expression of, 26 Immunosuppressive therapy for AS, 133 for inflammatory myopathies, 206–207 for RA, 94 for SSc, 120 Immunotherapy, 40 Impingement syndrome, 272 Inclusion body myositis (IBM), 198 See also Inflammatory myopathies age and, 198 Alzheimer’s and, 202 associations with malignancies of, 199 asymmetric pattern of, 197 cell-mediated mechanisms of muscle damage in, 201f characteristics of, 198t, 201 diagnosis of, 204–205 criteria for, 204t 337 Inclusion body myositis (IBM) (Cont.): dysphagia in, 199 endomysial inflammation in, 205 familial, 199 muscle biopsy for, 206f nonimmune factors in, 202 prognosis for, 207 retroviruses and, 202 T cell-mediated cytotoxicity in, 201 treatment for, 205–207 viral infections and, 202 Indirect alloreactivity, 52 Inducible co-stimulator (ICOS), 26 Infectious arthritis, 243 Neisseria gonorrhoeae and, 243 patient approach for, 243 prevention of, 251 rates of, 251 Staphylococcus aureus and, 243 Infertility, cyclophosphamide and, 163 Infiltrating tγδ cells, 166 Inflammasome, 188 Inflammatory back pain, 140f Inflammatory bowel disease (IBD), 130, 213f deformity and, 142 diagnosis of, 140f frank, 131 mediation of, 141 relapsing polychondritis and, 169t Inflammatory disease characterization of, 211 as crystal induced, 211 as idiopathic, 211 as immune related, 211 as infectious, 211 Inflammatory disease processes, molecules in, 39t Inflammatory effector molecules, 85 Inflammatory fluid, 219–220 Inflammatory myopathies, 197 See also Dermatomyositis; Inclusion body myositis; Polymyositis associated clinical findings of, 199 autoantibodies and, 200 clinical features of, 197 diagnosis of, 204–205 criteria for, 204t differential diagnosis of, 202–204 glucocorticoid therapies for, 205–206 immunogenetics and, 200 immunomodulation for, 207 immunosuppressive therapies for, 206–207 muscle biopsy for, 204 338 Inflammatory myopathies (Cont.): neck-flexor muscles in, 197 periodic paralysis in, 203 prednisone for, 205–206 prognosis for, 207 retroviruses and, 202 treatment for, 205–207 viral infections and, 202 Inflammatory peripheral joint synovitis, 140f Inflammatory response, 21 amplification of, 36 nonspecific, 86, 86f Infliximab, 40, 92–93 for AS, 133 for sarcoidosis, 182t, 183 Innate immune system, 3, activation of, 66 DCs and, 17 effector cells of, major components of, 6t PRRs of, 6t INR See International normalized ratio Insulin receptor, antibodies to, 61 Integrins, 6t, 7, 37f Intercellular adhesion molecule (ICAM-1), 110 Intercellular interactions, 10f Interferon γ, 47 production of, 62 Interferon (type II) receptor, 22 Interferons (IFNs), 66, 80 Interleukin (IL), 67f International normalized ratio (INR), 78 International Society of Nephrology (ISN), 68 lupus nephritis classification of, 69t Interstitial lung disease (ILD), 113, 115–116 chest radiography for, 116 detection of, 116 HRCT for, 116 PAH and, 116 progression of, 120 treatment for, 120 Interstitial nephritis, 126 Intestinal epithelium, 47 Intestinal motor function disturbance, 117 Intimal hypertrophy, 110 Intraarticular injections, 232t, 233 injury from, 264 Intracellular vesicles, 25 Intravenous immunoglobin (IVIg), 41t, 42 for ARF, 105 Index Invariant chain, 52 Ischemic bone necrosis, 70 Ischial bursitis, 271 ISN See International Society of Nephrology Isolated pulmonary metastasis, 269 Isolated vasculitis of CNS, 161 cerebral angiogram of, 162f definition of, 161 presentation of, 161 Isoniazid, 80 ITAM, 25f See Immunoreceptor tyrosine-based activation IVIg See Intravenous immunoglobin Ixodes tick, 247 J chain, 29 JAK, types of, 22 JAK3, mutations of, 22 Janus family of protein tyrosine kinases See JAK Joint(s) abnormalities of, 90 diagnostic imaging of, 220–222 mobility and, 118 in ARF, 102 evolution of, 223 hyperlipidemia and, 263 inflammation of, 118 injury to, 227 malalignment across, 227–228, 227f correction of, 231 pain, 87 with HOA, 267 OA and, 229–230 prosthetic, infection of, 250–251 protective mechanisms for, 224 repeated use of, 228 replacement of, 251 septic, 246 stability of, 214–215 swelling of, 87, 215 tumors of, 268–269 vulnerability of, 226, 311 Joint capsule, 224, 325 Joint loading, 226, 311 factors in, 227–228 obesity and, 227–228 Joint pseudowidening, 132 Jones criteria, 103 Jumper’s knee, 273 Juvenile arthritis, pauciarticular, 53t, 55, 212f Juvenile-onset spondyloarthritis definition of, 140–141 gender and, 141 symptoms in, 140 Juxtaarticular osteopenia, 261 Juxtaarticular osteoporosis, 136 Juxtaglomerular apparatus hyperplasia, 117 Kawasaki disease, 162 definition of, 317 thrombosis and, 317 Keratinocytes, 12t Keratoconjunctivitis sicca, 125, 127 See also Sicca syndrome Keratoderma blenorrhagica, 136 Kidneys function tests for, 294t sarcoidosis and, 178 in Sjögren’s syndrome, 126 SSc and, 112, 117–118 Killer cell-inhibitory cell receptor (KIR), 50 Killer immunoglobulin-like receptor (KIR), 137 KIR See Killer cell-inhibitory cell receptor; Killer immunoglobulinlike receptor Knee pain, 217–218 CPPD deposition disease and, 239 exercise and, 230–231 internal derangement and, 217 OA and, 224, 226, 229 treatment for, 230 from patellofemoral compartment, 231 surgery for, 233 Knock knees, 217, 227, 227f Kviem-Siltzbach procedure, 181 Kviem-Siltzbach reagent, 181 Kyphosis, dorsal, 259 Lambert-Eaton myasthenic syndrome, 202 Lamina propria See LP Laminin, 101 Large granular lymphocytes (LGLs), 3, 18 Lateral epicondylitis, 273 presentation of, 273 treatment for, 273–274 lcSSc See Limited cutaneous SSc Leflunomide, 94 Legg-Perthes disease, 227 Legionnaire’s disease, 203 Leishmania infection, 30 Index Lesch-Nyhan syndrome, 219 Lesional tissues, 111 Leucine-rich proteins, 6t, Leukemia inhibitory factor, 21 Leukocyte in CSF, 291t emigration of, 38 migration of, 36 polymorphonuclear, 40 in stool analysis, 293t Leukocyte Ig-like receptor (LIR), 50 encoding of, 50 Leukocytosis, 89 mild, 159 Leukopenia, 89, 118 LGLs See Large granular lymphocytes Life expectancy, with RA, 91 Ligaments, 224 tearing, 227 κ light chains, 28 Limb malalignment, 227f Limited cutaneous SSc (lcSSc), 107, 108t acro-osteolysis in, 115f calcium deposits with, 115 course of, 122 disease course of, 113–114 internal organ involvement in, 113t prognosis for, 122 renal involvement in, 114 Linkage disequilibrium, 47 Lipid membrane microdomains, 26 Lipid rafts, 26 Lipid transferases, 6t, Lipomas, 269 Lipopolysaccharide (LPS), 7, 7f ReA and, 135 Lipoprotein metabolism, 263 LIR See Leukocyte Ig-like receptor Lisfranc fracture-dislocation, 264 Listeria monocytogenes, 19 Lithium, 79 toxicology of, 288t Liver, 14t cholestatic, 193 sarcoidosis of, 177 LMP gene, 47 LMP2, 49 LMP7, 49 Löfgren’s syndrome, 174 Loss-of-function polymorphism, 59 Lovastatin, 80 Low-density lipoprotein cholesterol classification, 290t LP, 35f LPS See Lipopolysaccharide Lubricin, 224 Lumbar spine AS in, 130, 132 flexion of, 131 pain in, 130 Luminal occlusion, 110 Lungs HRCT of, 116f ILD, 113 sarcoidosis and, 175–176 SSc and, 111–112 volume of, 176, 297t Lupus, drug-induced, 79–80 Lupus dermatitis, 70–71, 79 Lupus nephritis, 73 classification of, 69t proliferative forms of, 77–78 treatment for, 69 Lupus pernio, 174, 176, 176f in African Americans, 176 Lupus profundus, 71 Lupus T cells, 66 Lyme disease, 203, 214, 247 criteria for, 316 fibromyalgia and, 256 treatment for, 247 Lymph node germinal centers, 27 Lymph nodes, 14t See also specific lymph nodes Lymphadenopathy, 116 Lymphatic filariasis, 250 Lymphocyte attachment, 37 homing, 38 percentage, in CSF, 291t rolling, 37 Lymphocyte-endothelial cell interactions first stage of, 37–38 molecular basis of, 36 second stage, 38 Lymphocytic meningitis, 178 Lymphoid organs, secondary, 27 Lymphoid precursor, 10f Lymphoid tissues, secondary, 14t Lymphoma See also Non-Hodgkin’s lymphoma ACE levels in, 179 CHOP regimen for, 128 in Sjögren’s syndrome, 126, 128f, 322, 325 Lymphomatoid granulomatosis, 150 Lymphotactin, 16t Lymphotoxin, 47 Lysine, 83 Lysis, 18, 19f 339 M cells See Membrane cells MAb See Anti-TNF-α monoclonal antibody Macrodantin, 80 Macroglossia, 193, 193f Macromolecule absorption, 33 Macrophage activation, 62 Macrophage scavenger receptors, Macrophages, 8, 9t See also Monocytes activated, 15 in bone marrow aspirates, 293t stressed, 15 Macular telangiectasia, 115 Maculopapular lesions, 177f in sarcoidosis, 176 MAdCAM-1 See Mucosal addressin cell adhesion molecule-1 Magnetic resonance imaging (MRI), 221t, 222 sensitivity of, 222f Major histocompatibility complex See MHC Malignant hypertension, 117 Malignant syndromes, 34t MALT See Mucosa-associated lymphoid tissue components of, 31–33 function of, 31 organization of, 31 Mannose receptor, 8t Mannose-binding lectin (MBL), activation pathway for, 20f Marenostrin, 184 Marfan’s syndrome, 317 Marie-Strümpell disease See Ankylosing spondylitis MASPs See MBL-associated serine proteases Mast cells, 9t, 12t, 20 activated, 84 Matrix metalloproteinases (MMPs), 225 Mauskopf appearance, 114–115 Mayaro virus, 249 MBL See Mannose-binding lectin MBL-associated serine proteases (MASPs), 21 McMurray test, 217 MCP See Monocyte chemotactic protein MCTD See Mixed connective tissue disease Mechanic’s hands, 198 Medial epicondylitis, 274 cause of, 274 differential diagnosis of, 274 340 Medial epicondylitis (Cont.): glucocorticoid therapies for, 274 presentation of, 274 treatment for, 274 Medial hypertrophy, 110 Median nerve enlargement, 259–260 Megakaryocytes, 11t, 15t in HOA, 266 Melphalan, oral, 193 Membrane attack complex, 40t Membrane cells (M cells), 31–33 Membranous lupus nephritis, 69t Memory B cell, 86 induction of, 27 Memory T cells, 86 Meniscus, 227 Mesangial proliferative lupus nephritis, 69t Mesenteric lymph node, 35f Metabolic myopathies, 202, 207 Metastatic calcification, 239 Metatarsal phalangeal joint (MTP), 223 Methotrexate, 95f administration of, 151 for nonsevere disease, 151 rituximab and, 94 for sarcoidosis, 182t toxic side effects of, 164t toxicology of, 288t Methotrexate b, 74t Methylprednisolone, 74t MGUS See Monoclonal gammopathy of uncertain significance MHC, 44 See also HLA expression of, 48 function of, 47, 320 genes in, 47 location of, 320 significance of, 45–46 structure of, 47 MHC class I molecules, 25, 46 biosynthesis of, 48, 49f disease associations of, 54 function of, 49 implications of, 320 structure of, 48 MHC class II molecules biosynthesis of, 49f, 52 function of, 52 implications of, 320 peptide binding to, 51f structure of, 50 MHC genotype, 60 MHC locus molecules, 34t MHC restriction, 48, 50 MHC-peptide complex, 48 Index Microangiopathic hemolysis, 118 Microbe recognition, Microbes, immune-mediated damage to, 35 Microbial antigens, 31 Microbial superantigens, 58 β2-microglobulin, 44 Microscopic hematuria, 117 Microscopic polyangiitis (MPA), 154 clinical manifestations of, 155 definition of, 154–155, 320 diagnosis of, 155 disease onset of, 155 with glomerulonephritis, 321 incidence of, 155 laboratory manifestations of, 155 PAN v., 312 pathogenesis of, 155 pathology of, 155 prevalence of, 155 recognition of, 320–321 treatment of, 155 Wegener’s granulomatosis v., 321 Microscopic polyarteritis, 154 Microstomia, 115 Microvascular injury, 83 Microvascular thrombotic crisis, 78 Midline destructive diseases, 150 Midline granuloma, 150 as idiopathic, 150 Migratory polyarthritis, 249 Minerals, trace, 290t Minimal mesangial lupus nephritis, 69t Minocycline, 80 for sarcoidosis, 183 Minor histocompatibility antigens, 52 Minor histocompatibility loci, 52 Mitochondrial cytochrome c, 35 Mitral valve flow through, 296t RHD and, 102 Mixed connective tissue disease (MCTD), 122 controversy of, 122 Sjögren’s syndrome and, 125t Mixed lymphocyte reaction, 46 MMPs See Matrix metalloproteinases Modified health assessment questionnaire, 214f Molecular mimicry, 58 Monarthritis, 135 acute, 219 chronic, 243 subacute, 243 Monarticular disease, 213, 218 Monoclonal antibodies, 41t to T/B cells, 42 Monoclonal gammopathy of uncertain significance (MGUS), 192 Monocyte chemotactic protein (MCP), 67f Monocyte percentage, in CSF, 291t Monocytes, 8, 10f, 11t–15t See also Macrophages in bone marrow aspirates, 293t Monosodium urate (MSU), 235, 236f gout and, 235 Morning stiffness, 211 with fibromyalgia, 255 in hemochromatosis, 260 Mortality nephritis and, 323 PAH and, 122 SSc and, 119, 122 MPA See Microscopic polyangiitis MRI See Magnetic resonance imaging MSU See Monosodium urate MTP See Metatarsal phalangeal joint Muckle-Wells syndrome (MWS), 185t, 187–188 Mucocutaneous lymph node syndrome, 162 Mucosa-associated lymphoid tissue (MALT), function of, 31 Mucosal addressin cell adhesion molecule-1 (MAdCAM-1), 38 Mucosal bacteria, 33 Mucosal surfaces, immunity at, 31 Multiple sclerosis, 42, 53t, 60t, 62t Mumps, 322 Muscle hemorrhage, 261 as protective element, 224 strength, 215 age and, 230–231 weakness, 226 with fibromyalgia, 257 Muscular dystrophy, 202, 207 Musculoskeletal disorders, 210 See also Articular disease age and, 212 articular involvement in, 213 articular v nonarticular, 210–211 chronology of, 213 clinical history of, 212–214 common conditions of, 213f determination of, 210 diagnostic algorithm for, 212f diagnostic imaging for, 220–222, 221t differential diagnosis of, 211–212 Index Musculoskeletal disorders (Cont.): drug-induced, 213t elderly with, 214 evaluation of, 211t familial aggregation in, 212 hyperlipidemia and, 263 incidence of, 210 inflammatory v noninflammatory, 211–212 laboratory investigations of, 218–220 pain level in, 214 physical examination of, 214–215 precipitating events for, 213 racial predilections for, 212 radiography for, 220 regional rheumatic complaints in, 215–218 rheumatic review of systems in, 213–214 with sickle cell disease, 261t terms used in, 215t topographic anatomical knowledge for, 214 Musculoskeletal system evaluation of, 210 sarcoidosis and, 178 MWS See Muckle-Wells syndrome Myalgias, 70 in inflammatory myopathies, 197 Myasthenia gravis, 42, 53t, 60t, 62t autoantibodies in, 61 Mycobacterial arthritis, 248 Mycobacterium tuberculosis, 173 Mycophenolate mofetil, 74t, 77, 79 Mycoplasma, 83 Myelodysplasia, 151 relapsing polychondritis and, 169t Myeloid dendritic cells, 9t, 10f, 15 Myeloma cells, 13t amyloidosis and, 191 Myeloperoxidase, antibodies to, 146 Myocardial inflammation, 102 Myocarditis, 118 Myofascial pain syndrome, 257, 268 characterization of, 268 massage for, 268 presentation of, 268 trigger points of, 268 Myofasciitis, 203 Myofibroblasts, 111 Myopathic potentials, 204 Myosin cross-reactivity, 101 Myositis, 119 See also specific types of myositis N-acetylglucosamine, 101 Narcolepsy, 53t Nasal septal perforation, 148 Natural cytotoxicity receptors (NCRs), 19 Natural killer cells (NK), 3, 10f, 11t–15t, 18 abilities of, 18 cell signaling by, 19 delayed hypersensitivity and, 39 hyporesponsiveness of, 18 receptors, 50 recognition of, 50 NCRs See Natural cytotoxicity receptors Neck-flexor muscles, 197 Necrosis, of digits, 114f Necrotizing myositis, PM v., 203 Negative selection, 24 Neisseria gonorrhoeae infectious arthritis and, 243 prevalence of, 244 Neonatal-onset multisystem inflammatory disease (NOMID), 185t, 187–188 Neovascularization, 83 Nephritis, 71, 314 mortality and, 323 Neurodegenerative disease, 189 Neurologic manifestations, of RA, 88 Neuropathic joint disease, 263 See also Charcot’s joint clinical manifestations of, 264 diabetes mellitus and, 263 diagnosis of, 264–265 disorders associated with, 264t joint distribution of, 263 mechanisms of, 264 pathology of, 264 pathophysiology of, 264 radiographic findings of, 265 treatment for, 265 Neutrophil(s), 9t, 11t, 18–19 accumulation of, 61 in bone marrow aspirates, 293t percentage, in CSF, 291t Neutrophilic granulocyte, 10f Nippostrongylus brasiliensis, 20 Nitric oxide (NO), 10, 225 NK See Natural killer cells NK-T cells, 9t, 19 NO See Nitric oxide Nociceptive fibers, 229 NOMID See Neonatal-onset multisystem inflammatory disease 341 Nonarticular disease, characterization of, 211 Noncaseating granuloma, 180 Nonerosive arthritis, 126 Nongonococcal bacterial arthritis antibiotics for, 246 arthroscopic drainage for, 246 clinical manifestations of, 245 epidemiology of, 245 laboratory findings on, 245–246 pain associated with, 245 pus drainage from, 246 single joint presentation of, 245 synovial fluid in, 245–246 treatment for, 246 Non-Hodgkin’s lymphoma, 191 Sjögren’s syndrome and, 322 Nonimmune factors, in IBM, 202 Noninflammatory disease characterization of, 211 as repetitive use injuries, 211 as trauma related, 211 Nonlymphoid organs, 23 Nonrheumatic disorders, 168 Nonspecific inflammatory response, 86, 86f Nonspecific interstitial pneumonitis, 116 Nonsteroidal anti-inflammatory drugs (NSAIDs), 73, 74t for ARF, 104 AS and, 133 for CaOx deposition disease, 242 directions for, 232 for gout, 237 for OA, 232–233, 232t RA and, 92 ReA and, 137 side effects of, 233 SLE and, 76 Normochromic anemia, 89–90 Normocytic anemia, 89–90 Normotensive renal crisis, 117 NSAIDs See Nonsteroidal anti-inflammatory drugs N-terminal 92 amino acids, 184 N-terminal trimming, 49f OA See Osteoarthritis Obesity arthritis and, 321 as joint loading factor, 227–228 OA and, 223, 311–312 Obliterative vasculopathy, 111 Obstructive disease, sarcoidosis and, 176 342 Ocular disease, 136 sarcoidosis and, 177 Oculo-facial-skeletal myorhythmia, 143 Oculomasticatory myorhythmia, 143 OKT3 therapy, 42 Olecranon bursitis, 271, 320 Oligoarthritis, 249 chronic seronegative, 263 Oligoarticular disease, 213 Oliguric renal failure, 118 Omalizumab, 42 Omega-3 fatty acids, RA and, 92 Onycholysis, 139f O’nyong-nyong virus, 249 Oophoritis, 30 Opiates, for OA, 232t Oral contraceptives, SLE and, 67 Organ-specific autoimmune disorders, 62t systemic v., 62 Orthostatic hypotension, 193 Orthotics, 231 for plantar fasciitis, 275 Osteoarthritis (OA), 211, 213, 223 acetaminophen for, 232t acromioclavicular joint in, 217 age and, 223–224, 226 arthropathy resemblance to, 259 calcium apatite deposition disease and, 240t capsaicin for, 232t cartilage in, 226 cartilage regeneration for, 233 clinical features of, 229–230 definition of, 223–224, 324 development of, 311 diagnosis of, 223 early changes in, 225 episodic pain in, 229 exercise and, 230–231 exercise as treatment for, 228 gender and, 311 generalized, 226 of hands, 224f treatment for, 230 of hip, 226 incidence of, 318 joint pain and, 229–230 joints affected by, 223, 223f of knees, 224, 226, 229 treatment for, 230 medial, 230f nonpharmacotherapy for, 230 NSAIDs for, 232–233, 232t obesity and, 223, 311–312 opiates for, 232t osteophytes in, 228 Index Osteoarthritis (OA) (Cont.): pain sources in, 229 pathologic changes of, 228f pathology of, 228–229 pharmacotherapy for, 231–233, 232t presentation of, 216 prevalence of, 224 radiographic findings of, 230 repeated joint use and, 228 risk factors for, 226–228, 226f genetics and, 226 global consideration of, 226–227 heritability of, 226 in joint environment, 227 loading factors as, 227–228 systemic, 226 surgery for, 233 symptoms of, 223 synovitis and, 229 treatment for, 230–233, 324 x-ray evidence of, 224, 230f Osteolysis, 118 Osteopenia, 89 Osteophytes, 223 formation of, 228 as pain source, 229 Osteoporosis juxtaarticular, 136 RA and, 89 of spine, 131 Ovarian failure, cyclophosphamide therapy and, 77 Overlap syndromes, 199–200 Oxalosis primary, 240–241 treatment for, 242 secondary, 241 Pachydermoperiostosis, 266 PACNS See Primary angiitis of CNS PAD14, 83 PAH See Pulmonary arterial hypertension Palpable purpura, 146, 159, 162 PAMPs See Pathogen-associated molecular patterns PAN See Polyarteritis nodosa pANCA See Perinuclear antineutrophil cytoplasmic antibodies Pancytopenia, 177 PANDAS See Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Paracetamol See Acetaminophen Parasitic arthritis, 250 Paraspinal calcifications, 115 Parathyroid hormone (PTH), 178 clinical chemistry of, 285t Parotid gland, bilateral enlargement of, 126t Parrot’s pseudoparalysis, 247 Patellar braces, 231 Patellar tendinitis, 273 Pathogen diversity, 52–53 Pathogen-associated molecular patterns (PAMPs), 3, 30 conservation of, Pathogenesis, immunologic component of, 54 Pathogenic autoreactivity, 31 Pathogenic immune-complex formation, 144–145 Pathogenic T lymphocyte responses, 146 Patient care, RA and, 94–95 Pattern recognition receptors (PRRs), 3, 6t, of innate immune system, 6t role of, 8t Pauciarticular disease, 213 PCR See Polymerase chain reaction PDGF See Platelet-derived growth factor Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), 103 Pemphigus foliaceus, 62t Pemphigus vulgaris, 53t, 55, 60t, 62t Penicillin, 103, 106 Pentraxins, 6t Peptide antigen presentation, 49 Peptide sequence-dependent bonding, 48 Peptide sequence-independent bonding, 48 Peptide-binding groove, 52 B pocket in, 54 Peptides antigenic, 56 binding abilities of, 48, 51f intracellular generation of, 50 length of, 51 TAP transport of, 49 Perforin, 34t Periarticular disorders, of extremities, 271 Perifascicular atrophy, 201 Perinuclear antineutrophil cytoplasmic antibodies (pANCA), 145, 317 Periodic fever with aphthous ulcers, pharyngitis and cervical adenopathy (PFAPA), 186 Periodic paralysis, 203 Index Periorbital ecchymoses, 193f Periostitis, 267 Peripheral blood lymphocytes, 18, 26 Peripheral lymphapheresis, 84 Peripheral node addressin (PNAd), 38 Peripheral synovitis, 130 Perivascular infiltrate, 83 Pernicious anemia, 60t, 62, 62t Persistent inflammatory synovitis See Rheumatoid arthritis Peyer’s patches, 35f, 38 PFAPA See Periodic fever with aphthous ulcers, pharyngitis and cervical adenopathy PFT See Pulmonary function testing Phagocytosis, 36 Phlebotomy, 260 Phospholipid-β2-glycoprotein I complex, 61 Photosensitivity, 125 Pigmented villonodular synovitis, 268–269 clinical picture of, 269 presentation of, 315 symptoms of, 269 treatment for, 269 PIP See Proximal interphalangeal joints Plantar fasciitis, 274–275 cause of, 315 diagnosis of, 274 differential diagnosis for, 274 glucocorticoid therapies for, 275 incidence of, 274 long-term studies of, 274–275 massage for, 275 night splinting of, 275 orthotics for, 275 radiography of, 274 rupture, 275 surgery for, 275 treatment of, 274–275, 315 Plasma cells antibody-producing, 84 in bone marrow aspirates, 293t Plasma pentraxins, Plasmacytoid f dendritic cells, 9t, 10f, 15 Plasmapheresis, 151 Platelet aggregation, 120 Platelet-activating factor, 20t Platelet-derived growth factor (PDGF), 110 Platelets, 15t Pleural fluid complement, 88 Pleuritis, 88 Pleuropulmonary manifestations, 88 PM See Polymyositis PMNLs See Polymorphonuclear leukocytes PNAd See Peripheral node addressin Pneumococcal infections, 245 Pneumocystis carinii, 36 Pneumocystis jiroveci, 164 Pneumocystis pneumonia, 176 Polyangiitis overlap syndromes, 162 Polyarteritis nodosa (PAN), 145, 153, 163 clinical manifestations of, 153, 154t, 312 definition of, 153 diagnosis of, 154 fibrinoid necrosis in, 153 hepatitis B and, 312, 319–320 hypertension with, 154 incidence of, 153 laboratory manifestations of, 153 MPA v., 312 organ systems involved in, 153, 154t pathogenesis of, 153 pathology of, 153 prevalence of, 153 renal involvement in, 153, 154t symptoms of, 312 treatment for, 154 Polyarthritis, 70, 91 chronic, 86 migratory, 249 Polyarticular arthritis, 244t Polyarticular disease, 213 Polyclonal B cell activators, 59 Polymerase chain reaction (PCR), sensitivity of, 136 Polymeric protein deposition, 189 Polymorphism, 44, 46 genetic, 51 loss-of-function, 59 Polymorphonuclear cells, 17 Polymorphonuclear leukocytes (PMNLs), 85, 220f increase in, 91 Polymyalgia rheumatica, 203, 211, 212f definition of, 155 prednisone for, 157 treatment of, 156–157 Polymyositis (PM), 118, 197 See also Inflammatory myopathies associations with malignancies of, 199 cell-mediated mechanisms of muscle damage in, 201f characteristics of, 198t, 201 diagnosis of, 204–205 criteria for, 204t dysphagia in, 199 extramuscular manifestations of, 199 inflammation in, 205 343 Polymyositis (PM) (Cont.): muscle biopsy for, 205f necrotizing myositis v., 203 occurrence of, 198 onset of, 197–198 presentation of, 314, 323 presumption of, 207 retroviruses and, 202 symmetric pattern of, 197 T cell-mediated cytotoxicity in, 201 treatment for, 205–207 viral infections and, 202 Positive selection, 24 Postinfectious arthritis, 250 Post-streptococcal reactive arthritis (PSRA), 103 Post-streptococcal syndromes, 103 Precursor cells, Prednisone for amyloidosis, 193 for inflammatory myopathies, 205–206 for polymyalgia rheumatica, 157 for sarcoidosis, 182t Pregabalin, 257 Pregnancy AS and, 134 SLE and, 78, 316 SSc and, 118 Prepatellar bursitis, 272 Primary angiitis of CNS (PACNS), 161 Primary antibody response, 29 Primary biliary cirrhosis, 163 relapsing polychondritis and, 169t Sjögren’s syndrome and, 125t Primary oxalosis, 240–241 treatment for, 242 Primary prophylaxis, 105–106 Prognostic significance, 90 Programmed cell death See Apoptosis Progressive flexion contractures, 113 Proinflammatory TNF α, 66 Proliferative glomerulonephritis, 312 Prophylaxis, 105–106 Propionibacterium acnes, 142, 173 Proprioception, impaired, 227 Propylthiouracil, 162 Prosthetic joint infection, 250 surgery for, 250 treatment for, 250–251 Protease distribution, 52 Protease granzyme B, 110 Proteasome, 25 Proteoglycan depletion, 168, 228 Proximal interphalangeal joints (PIP), 138, 216 PRRs See Pattern recognition receptors 344 PsA See Psoriatic arthritis Pseudo-ankylosing spondylitis, 235t Pseudoarthrosis, 131 Pseudogout, 211, 238, 312–313 Pseudomonas aeruginosa, 246 Pseudo-rheumatoid arthritis, 235t Psoralen plus ultraviolet light (PUVA), 140 Psoriasis vulgaris, 53t, 54 history of, 322 HIV and, 138 predisposition for, 67 PsA and, 137 Psoriatic arthritis (PsA), 137 background on, 137 characteristic lesions of, 139f classification schemes for, 138 clinical features of, 138 definition of, 137 diagnosis of, 139, 140f DIP in, 136, 138 epidemiology of, 137 features of, 138 HIV and, 140 joint involvement in, 321 juvenile onset of, 137 laboratory findings of, 139 nail changes in, 138, 321–322 outcomes of, 138 pathogenesis of, 138 pathology of, 137–138 PIP in, 138 presentation of, 321 psoriasis and, 137 RA and, 137–138 radiographic findings of, 139 skin/joint therapy for, 139–140 surgery and, 140 synovium of, 138 treatment for, 139–140 Psoriatic arthropathy, 137 Psoriatic spondylitis, 53t PSRA See Post-streptococcal reactive arthritis PTH See Parathyroid hormone PTPN22, 59 identification of, 83 Pulmonary arterial hypertension (PAH), 107, 108t, 115–117 as asymptomatic, 116 doppler echocardiography for, 116 ILD and, 116 mortality and, 122 sarcoidosis and, 176 treatment for, 121 Index Pulmonary artery vasculitis, 167 Pulmonary compliance, 297t Pulmonary epithelial cells, 14t Pulmonary fibrosis, 88, 108t SSc and, 107, 111, 121 Pulmonary function testing (PFT), 116 Pulmonary mechanics, 297t Pulmonary physiology, useful values for, 297t PUVA See Psoralen plus ultraviolet light Pyogenic infections, 40t Pyrimidine synthetase inhibitor leflunomide, 140 Pyrin, 184 PYRIN domain, 184, 188 De Quervain’s tenosynovitis, 216, 273 definition of, 273, 320 treatment for, 320 RA See Rheumatoid arthritis Radiation-derived units, 298t Radionuclide scintigraphy, 220, 221t RAG, 24 See Recombinase activating genes RAG1, 24 RAG2, 24 Range of motion, 215, 215t Rare immune-complex disease, 40t Rare Neisseria infections, 40t Raynaud’s phenomenon, 107, 108t, 109, 113, 114, 200 absence of, 119 dcSSc and, 113 family history of, 114 fibromyalgia and, 255 Sjögren’s syndrome and, 128f treatment for, 120 in women, 114 Raynaud’s-like episodic vasospasm, 118 ReA See Reactive arthritis Reactive arthritis (ReA), 53t, 54, 134, 214, 250 background on, 134 Campylobacter species and, 134 Chlamydia trachomatis and, 134 clinical features of, 135 definition of, 134 diagnosis of, 136–137, 140f [99mTc]diphosphonate scintigraphy of, 221f disseminated gonococcal disease, 136 epidemiology of, 134–135 Reactive arthritis (ReA) (Cont.): gender ratio in, 134 laboratory findings on, 136 LPS and, 135 manifestations of, 136 NSAIDs for, 137 pathology of, 135 presentation of, 315 radiographic findings on, 136 sacroiliitis with, 136 Salmonella and, 134 spinal fusion in, 136 spondylitis with, 136 symptoms of, 135 treatment for, 137 triggering of, 134–135 Yersinia and, 134, 136 Recombinase activating genes (RAG), 24 Recurrent Neisseria infections, 40t Reflex sympathetic dystrophy syndrome, 268, 313 Reiter’s syndrome, 53t, 171, 211 Relapsing polychondritis, 168, 312 aortic regurgitation and, 170–171 clinical manifestations of, 169–171, 169t complement deposits in, 169 diagnosis of, 171, 322 diagnostic criteria for, 168 disorders associated with, 169 ear involvement and, 169–170, 170f eye involvement and, 170 Ig deposits and, 169 laboratory findings of, 171 laryngotracheobronchial involvement and, 170 manifestations of, 168 onset of, 322 pathology of, 168–169 pathophysiology of, 168–169 RA and, 171 SLE and, 171 symptoms of, 322 systemic vasculitis and, 171 treatment of, 171–172 Relative risk, 53–54 Renal amyloidosis, 192 Renal function tests, 294t Renal Pathology Society (RPS), 68 lupus nephritis classification of, 69t Renal tubular acidosis Sjögren’s syndrome and, 128f, 313 treatment of, 128 Renin secretion, 117 Renin-angiotensin axis activation, 117 Repetitive use injuries, 211, 228 Index Respiratory epithelium, 12t Respiratory tract infection,ARF and, 100 Restriction element, 50 Retrocalcaneal bursitis, 271 Retroperitoneal fibrosis, 163 in AS, 131 Retroviral antigens, 202 Retroviruses, inflammatory myopathies and, 202 RHD See Rheumatic heart disease Rheumatic carditis, 102 Rheumatic fever See Acute rheumatic fever Rheumatic heart disease (RHD), 100 See also Acute rheumatic fever criteria for, 104t diagnosis of, 104t as disease of poverty, 100 heart involvement in, 102 incidence of, 100 incidence reduction of, 100 mitral valve and, 102 pathogenetic pathway for, 102f prevalence of, 100, 101f Rheumatoid arthritis (RA), 53t, 60t, 82, 312 acromioclavicular joint in, 217 in African Americans, 318 anti-TNF-α therapy for, 315 approach to patient with, 94–95 biologics for, 93–94 classic approach to, 95 classification of, 91, 91t clinical course of, 90–91 clinical manifestations of, 86–89 definition of, 324 demographics of, 82–83 diagnosis of, 89, 91, 324 disability and, 87, 90–91 DMARDs and, 92–93, 95 response to, 93, 96 drugs for, 92–93 in elderly, 89 epidemiology of, 82–83 etiology of, 83, 91–92, 323 evaluation of, 89 extraarticular manifestations of, 87–89 familial predisposition for, 318 folic acid and, 93 folinic acid and, 93 genetics and, 82–83 glucocorticoid therapies for, 92–93, 95 heart disease and, 88, 92 HLA and, 55 Rheumatoid arthritis (RA) (Cont.): immunosuppressive therapy for, 94 incidence of, 82–83 joints commonly affected by, 90 laboratory findings on, 89–90 median life expectancy with, 91 medical management of, 92, 95f neurologic manifestations of, 88 NSAIDs and, 92 omega-3 fatty acids and, 92 onset of, 86–87, 95 osteoporosis and, 89 palliative care for, 92 pathogenesis of, 83–86 pathology of, 83–86 patient care and, 94–95 predisposition for, 82 prevalence of, 82, 318 prognosis for, 90–91 propagation of, 84 PsA and, 137–138 radiographic evaluation of, 90 relapsing polychondritis and, 169t, 171 remissions of, 90 risk for, 83 severity of, 82 signs of, 87 Sjögren’s syndrome and, 125t, 126 skeletal muscle and, 88 SSc and, 119 surgery for, 94, 96 symptoms of, 87 nonspecific, 91 as systemic, 87–88 systemic manifestations of, 85 therapeutic goals for, 91–92 TNF and, 85 treatment for, 91–94 window of opportunity for, 95 twins and, 82 Rheumatoid factor, 318 conditions associated with, 89 high titers of, 90 positive test for, 91 presence of, 89 prevalence of, 324 serologic tests for, 219 Rheumatoid inflammation, 85 Rheumatoid nodules, 88 Rheumatoid synovitis B cells and, 84 histology of, 84f progression of, 86f Rheumatoid synovium, 83 characterization of, 84 345 Rheumatoid vasculitis,African Americans and, 88 Rituximab, 63, 85 methotrexate and, 94 Rocker foot, 264 Rolling, 37 Ross River virus, 249 Rotator cuff tendonitis, 217, 272, 321 presentation of, 272 treatment for, 272, 321 RPS See Renal Pathology Society Rubella virus, 249 Saccharomyces cerevisiae, 322 Sacroiliitis, 130 with AS, 132f, 325 with ReA, 136 Saddle nose, 170f, 322 Salicylates, 74t ARF and, 102, 104 toxicology of, 288t Salmonella ReA and, 134 sickle cell disease and, 262 Sapho syndrome, 142 Sarcoidosis, 173 acute v chronic, 181f airway involvement in, 176 animal model of, 173 anti-TNF therapy for, 183 BAL for, 174, 181 bone cysts with, 179f bone marrow involvement in, 177 calcium metabolism and, 178 cardiac involvement in, 178 chest scan for, 176f chronic inflammatory lesions in, 176f clinical manifestations of, 175 CNS and, 178 common drugs for, 182t complications of, 179 CSF and, 178 definition of, 173 demographics of, 175 diagnosis of, 180–181 environmental agents of, 173 etiology of, 173 glucocorticoid therapies for, 182–183 granuloma formation in, 173, 180 helper T cells in, 174 HIV and, 174 immunopathogenesis of, 174 incidence of, 174 infiltrates in, 175 346 Sarcoidosis (Cont.): infliximab for, 183 initial events of, 174f initial presentation of, 181 kidney involvement in, 178 laboratory findings on, 179–180 lifetime risk of, 175t liver involvement in, 177 lung involvement in, 175–176 maculopapular lesions in, 176, 177f management of, 181–183, 181f, 182f multiorgan, 181–182 musculoskeletal involvement in, 178–179 obstructive disease and, 176 ocular involvement in, 177f organ involvement in, 175 other organ involvement in, 179 PAH and, 176 pathophysiology of, 174 patient management for, 180f prevalence of, 174 prognosis for, 181 respiratory complaints with, 175 Sjögren’s syndrome and, 127t skin biopsy for, 180 skin involvement in, 176 skin lesions in, 175 spleen involvement in, 177 standardized scoring system for, 175 symptoms of, 175 testing for, 180–181 topical therapy for, 181 treatment for, 181–183, 182t Sausage digit, 135, 315 Scavenger receptors, 6t Schirmer’s test, 324 Schober test, 131 Sciatica, 268 SCLE See Subacute cutaneous lupus erythematosus Scleredema, 119 Sclerodactyly, 107, 115f, 119, 122 Scleroderma, 107, 113, 214 See also Systemic sclerosis Sjögren’s syndrome and, 125t Scleroderma renal crisis, 108t, 117 onset of, 118 treatment for, 121 Scleroderma-like induration, 122 conditions associated with, 108t Scleromyxedema, 119 SCT See Stem cell transplantation Secondary amyloidosis, 189, 313 Secondary oxalosis, 241 Index Secondary prophylaxis, 105–106 suggestion duration of, 106t Secondary syphilis, 248 Secondary vasculitis, 162–163 Secretory IgA, 33 Secretory protein, 29 Selectins, 37f Selective serotonin reuptake inhibitors (SSRIs), 257 Self recognition, 57 Self-antigens expression of, 31 immune response to, 61 sequestration of, 58t in thymus, 31 Self-peptide recognition, 24 Self-reactive antibodies, 28 Self-reactive T lymphocyte, 56 Senile systemic amyloidosis, 195 Sensory afferents, 224 Sensory trigeminal neuropathy, 118 Septic arthritis, 236 in hemophilia, 261 presentation of, 321 risk for, 313 sickle cell disease and, 262 Serology, 46 Serotonin metabolites, 254, 286t Serum amyloid A, 313 Serum immunoglobulin, 29 Serum muscle enzymes, 204 Serum rheumatoid factor, 90 Serum sickness, 163 vasculitis and, 145 Serum sickness-like reactions, 163 Serum uric acid, 218–219, 236 Shared epitope, 55, 83 Shawl sign, 198 Shigella species, 135 Shoulder, coronal section of, 272f Shoulder pain, 216–217 adhesive capsulitis, 273 rotator cuff tendinitis and, 272, 321 treatment of, 321 Sicca syndrome, 75, 118 See also Keratoconjunctivitis sicca Sjögren’s syndrome and, 127t symptoms of, 126t Sickle cell crisis, 261–262 Sickle cell dactylitis, 261 Sickle cell disease, 261 bone infarction with, 262 bone marrow hyperplasia in, 262 musculoskeletal abnormalities with, 261t Sickle cell disease (Cont.): osteomyelitis development with, 262 Salmonella and, 262 septic arthritis and, 262 thrombosis secondary to, 262 Signal transducers and activators of transcription (STATs), 22 Signaling pathways, 22 Signaling proteins, 34t Simvastatin, 80 Single breath diffusing capacity (DLCO), 116 Single nucleotide polymorphism (SNP), SSc and, 108 Sjögren’s syndrome, 53t, 62t, 118, 122, 124 arthritis and, 128f autoimmune disorders and, 125t chronic active hepatitis and, 125t classification criteria for, 127t clinical manifestations of, 125–126 congenital heart block and, 126 definition of, 124 diagnosis of, 126 differential diagnosis of, 126, 127t DM and, 199 extraglandular manifestations of, 128f gender and, 324 glandular manifestations of, 128f HIV infection and, 127t incidence of, 124 lymphoma in, 126, 128f, 325 MCTD and, 125t misdiagnosis of, 257 non-Hodgkin’s lymphoma and, 322 ocular involvement in, 125 pathogenesis of, 124 photosensitivity and, 125 presentation of, 313, 324 prevalence of, 124 primary, extraglandular manifestations in, 125t primary biliary cirrhosis and, 125t primary v secondary, 124 principal oral symptom of, 125 RA and, 125t, 126 Raynaud’s phenomenon and, 128f relapsing polychondritis and, 169t renal involvement in, 126 renal tubular acidosis and, 128f, 313 sarcoidosis and, 127t scleroderma and, 125t sera in, 124 Sicca syndrome and, 127t SLE and, 125t Index Sjögren’s syndrome (Cont.): treatment of, 127–128 algorithm for, 128f vasculitis and, 128f Skeletal muscle, RA and, 88 Skin care of, 121 induration of, 119 lesions of, 115, 159, 175 SSc and, 111 Skin thickening, 107, 114 Skinfold tenderness, 256 SLE See Systemic lupus erythematosus Sleep disturbance, fibromyalgia and, 254, 318 Slipped femoral capital epiphysis, 227 Small intestine, 14t Smooth-muscle-like myofibroblasts, 111 SNP See Single nucleotide polymorphism Somatic mutation, 27 Specificity, SPEP See Standard serum protein electrophoresis Spinal fracture, 131 Spinal fusion, with ReA, 136 Spinal inflammation, 132f Spinal mobility, in AS, 131 Spinal stenosis, 235t Spinocerebellar ataxia, 54 Spirochetal arthritis, 247 Spirometry, 297t Spleen, 14t sarcoidosis and, 177 Spondylitis, with ReA, 136 Spondyloarthritides, 129 See also specific types of spondyloarthritides diagnosis of, 140f relapsing polychondritis and, 169t world wide spread of, 134–135 Spondyloarthropathies, 53t, 54, 212 mediation of, 141 Spondylodiscitis, with AS, 132f Spontaneous pneumothorax, 115 SSA See Sulfasalazine SSc See Systemic sclerosis SSc sine scleroderma, 107, 113 SSRIs See Selective serotonin reuptake inhibitors Standard serum protein electrophoresis (SPEP), 192 Staphylococcus aureus, 40 infectious arthritis and, 243 prevalence of, 244 in Wegener’s granulomatosis, 148 STATs See Signal transducers and activators of transcription STATs, domains of, 22 Stem cell, 10f Stem cell transplantation (SCT), 42 See also Hematopoietic stem cell transplantation for amyloidosis, 193 Sterile inflammatory effusion, 261–262 Sticking, 38 Stiff-man syndrome, 62t Stool analysis, 293t Streptococcal antibody testing, 101 Streptococcal infections, 105 Streptococcal M protein, 101 Streptococci, group A, 100 ARF and, 103, 326 Streptococci, group C, 100 Streptococci, group G, 100 Streptococcus pneumoniae, 30 Stromal cells, 12t Subacromial bursitis, 216, 271 surgical decompression of, 272 Subacute bacterial endocarditis, 29 vasculitis and, 163 Subacute cutaneous lupus erythematosus (SCLE), 70 rash of, 71 Subacute monarthritis, 243 Subchondral granulation tissue, 130 Subcutaneous nodules, from ARF, 103 Subdeltoid bursitis, 271 Subluxation, 215, 215t, 318 Sulfasalazine (SSA), 80, 95f Superficial vein thrombosis, 167 Supraspinatus tendon tearing, 272 Surgery antibiotics before, 251 bacterial infection from, 244 for hip pain, 233 for knee pain, 233 for OA, 233 for plantar fasciitis, 275 for prosthetic joint infection, 250 PsA and, 140 for RA, 94, 96 for subacromial bursitis, 272 Swan-neck deformity, 87 Sydenham’s chorea, 102–103 Sympathetic ophthalmia, 62t Symptomatic arthritis, 83 Syndesmophytes, 139 Synovial chondromatosis, characterization of, 269 Synovial effusion, 214 347 Synovial fibroblasts, 84 Synovial fluid analysis of, 90, 315 aspiration of, 219, 243 interpretation of, 220f calcium apatite aggregates in, 240, 241f exudation of, 85 hemorrhagic, 220 inoculation of, 246 in nongonococcal bacterial arthritis, 245 normal, 243 as protective element, 224 Synovial histology, 135 Synovial hypertrophy, 214 Synovial inflammation, 82, 87 Synovial lining cells hyperplasia of, 83 hypertrophy of, 83 Synovial osteochondromatosis, 235t, 269 Synovial sarcoma, 269 Synovial tissue, 84 Synovitis, 87, 318 AS and, 130 chronic nonsymmetric, 236 OA and, 229 peripheral, 130 persistent, 90 pigmented villonodular, 268–269 clinical picture of, 269 symptoms of, 269 treatment for, 269 SSc and, 112 Synovium, 225 bacterial infection of, 244 role of, 229 thalassemia and, 262 Syphilis, secondary, 248 Syphilitic arthritis, 247–248 Systemic amyloidosis, 189 Systemic autoimmune disorders, 62t organ-specific v., 62 Systemic immune compartment, 201f Systemic lupus erythematosus (SLE), 42, 53t, 59, 60t, 62, 62t, 66, 211, 212f See also Lupus nephritis analgesics for, 76 antimalarials for, 76 antiphospholipid antibody syndrome, 78 autoantibodies in, 68t cardiac manifestations of, 73–75 clinical manifestations of, 72t interpretation of, 70 CNS manifestations of, 73 348 Systemic lupus erythematosus (SLE) (Cont.): cutaneous manifestations of, 70–71 definition of, 66, 319 diagnosis of, 69, 323 algorithm for, 71f criteria for, 69, 70t standard tests for, 76 disability and, 79 drug-induced, 79–80 environmental stimuli and, 67 etiology of, 66 experimental therapies for, 79, 80f fetal loss and, 78 following disease course of, tests for, 76 gastrointestinal manifestations of, 75 glucocorticoid therapies for, 70, 77 hematologic manifestations of, 75 initial therapy for, 71f laboratory tests for, 75–76 life-threatening, 77 maternal, 78 medications for, 74t–75t misdiagnosis of, 257 as multigenic disease, 66–67 musculoskeletal manifestations of, 70 NSAIDs and, 76 ocular manifestations of, 75 overview of, 70 pathogenesis of, 66, 67f pathology of, 68 patient outcome and, 79 predisposition to, 67 pregnancy and, 78, 316 presentation of, 314 prevalence of, 66 preventative therapies for, 79 prognosis of, 79 as prototype, 145 pulmonary manifestations of, 73 rash of, 71 relapsing polychondritis and, 169t, 171 renal manifestations of, 71–73 reversibility of, 68 sex and, 67 Sjögren’s syndrome and, 125t special conditions and, 78–79 SSc and, 119, 122 survival and, 79 systemic manifestations of, 70 treatment for, 76–77, 319, 323 vascular occlusions and, 73 Systemic necrotizing vasculitis, 19, 62t Systemic sclerosis (SSc), 107 See also Diffuse cutaneous SSc; Limited cutaneous SSc; Scleroderma ANA in, 118 Index Systemic sclerosis (SSc) (Cont.): animal models of disease, 109 autoantibodies in, 110, 113t, 119 cellular autoimmunity and, 110 chronic nonprogressive proteinuria in, 117 clinical features of, 112–114 course of, 121–122 cyclophosphamide for, 120 definition of, 107 diagnosis of, 119 disease manifestations with, 118 disease-modifying treatments for, 120–121 edema and, 114 endothelial cell injury in, 110 environmental factors of, 108–109 epidemiology of, 107–108 established, 115 fibroblasts of, 111 fibrosis and, 110–111 gastrointestinal tract and, 112, 117 treatment for, 121 genetic considerations of, 108 geographic clustering of, 108–109 glucocorticoid therapies for, 120 heart disease and, 112, 118 as highly heterogeneous, 107 history of, 121 humoral autoimmunity and, 110 hypertension in, 117 ILD and, 115–116 immunosuppressive therapy for, 120 incidence of, 107–108 initial clinical presentation of, 113–114 internal organ involvement in, 113t in kidneys, 112, 117–118 treatment for, 121 laboratory features of, 118–119 lungs and, 111–112 mortality and, 119, 122 musculoskeletal complications of, 118 PAH and, 115–117 pathogenesis of, 109–111, 109f pathologic findings in, 112 pathology of, 111–112 pregnancy and, 118 presentation of, 108 prognosis for, 121–122 pulmonary features of, 115–117 pulmonary fibrosis and, 107, 111 RA and, 119 risk of, 109 Systemic sclerosis (SSc) (Cont.): serum iron in, 118 skin and, 111, 114–115 care of, 121 SLE and, 119, 122 SNP and, 108 subsets of, 108t synovitis and, 112 TNF-α and, 108 treatment of, 119–121 vasculopathy and, 109 Systemic vasculitis, relapsing polychondritis and, 171 T cell(s), 3, 11t–15t, 22 activated, 13t, 63 activity of, 59 amplification of, 86f anergic v tolerant, 26 autoreactivity of, 31 B cells and, 30 development of, 23f fate of, 56 in exocrine glands, 124 peripheral, 31 precursors of, 23 proliferation of, 84 regulation of, 59 sensitization of, 101 soluble, 41t T cell receptor for antigen, 3, 10f γδ form, 84 signaling through, 25f T cell recognition (TCR) of antigen, 24 diversity of, 24 trimolecular complex of, 45f T cell superantigens, 26 T cell-mediated cytotoxicity, in PM/IBM, 201 T cell-mediated inflammation, 35f T lymphocytes, 22 See also Cytolytic T lymphocytes mature, 22 recognition by, 46 stimulation of, 59 T regulatory cells, 30 loss of, 30 Tabes dorsalis, 263–264 Takayasu’s arteritis, 42, 147, 157 arteriographic abnormalities in, 158t clinical manifestations of, 157 definition of, 157 diagnosis of, 157 incidence of, 157 349 Index Takayasu’s arteritis (Cont.): laboratory manifestations of, 157 pathogenesis of, 157 pathology of, 157 prevalence of, 157 treatment of, 158 TAP proteins, 25, 48 See Transporters associated with antigen processing peptide transport by, 49 Target cell lysis, 19f TCR See T cell recognition TCRαβ cell receptor, 25 TCRαβ cells, 24 TCRγδ, 24 TCR-MHC binding, 26 Temporal arteritis, 155 Tendinitis, 136, 235t glucocorticoid therapy for, 137 Tendon friction rubs, 117–118 Tendon rupture, 235t Tennis elbow, 273–274 Tenosynovitis, 216, 247 See also Bicipital tendinitis De Quervain’s, 216, 273 Tetracycline, 121 TGF See Transforming growth factor TGF-β See Transforming growth factor β;Transforming growth factor β β-Thalassemia characterization of, 262 hemochromatosis and, 262 major/intermedia, 262 minor, 263 onset of, 262 synovium in, 262 Therapeutic drug monitoring, toxicology and, 287t–289t Thoracic duct drainage, 84 Thrombocytopenia, 117, 118 Thrombocytosis, in Wegener’s granulomatosis, 150 Thrombophlebitis, 167 Thrombosis, 83 Kawasaki disease and, 317 sickle cell disease and, 262 Thrombotic thrombocytopenic purpura, 78 Thymic epithelial cells, 12t, 13t self-peptides on, 24 Thymocytes, 22 maturation of, 24 Thymus, 10f, 14t self-antigens in, 31 Thyroid acropachy, 267 Thyroid-stimulating hormone (TSH), 61 clinical chemistry of, 286t Tietze syndrome, 268 onset of, 268 treatment for, 268 Tissue fibrosis, 120 TLR See Toll-like receptor proteins TLR2, 8t TLR3, 8t TLR4, 8t TLR5, 8t TLR7/8, 8t TLR9, 8t TLR10, 8t TNF blocking agent for, 94, 95f neutralization of, 93 RA and, 85 tuberculosis and, 93 TNF inhibitors, 80 TNF (type III) receptor family, 22 TNF receptor-associated periodic syndrome (TRAPS), 185t, 187 TNF-α, 47 blockade of, 130 SSc and, 108 TNF-β, 47 TNF-R, 35 See Tumor necrosis factor receptor Tolerance, 3, 58 maintenance of, 48 Tolerance induction, 42 Toll-like receptor proteins (TLR), 7, 7f Toll-like receptors, 6t Tophaceous deposits, 235 Topical glucocorticoids, 74t Topoisomerase-1 antibody, 119 Total cholesterol classification, 290t Touraine-Solente-Golé syndrome, 266 Toxic oil syndrome, 109 Toxicology, therapeutic drug monitoring and, 287t–289t Transendothelial migration, 38 Transforming growth factor (TGF), 66 Transforming growth factor β (TGF-β), 84, 109 signaling, 111 Transient ischemic attacks, prevalence of, 73 Transmembrane helix family, 22 Transporters associated with antigen processing (TAP proteins), 25 Transthyretin (TTR), 195 TRAPS See TNF receptor-associated periodic syndrome Triacylated lipopeptides, 7f Trimethoprim-sulfamethoxazole, 152 Trimolecular complex, of TCR, 45f Trochanteric bursa, 218, 271 Trochlear sulcus, 231 Tryptophan-serine-X-tryptophan-serine (WSXWS), 21 TSH See Thyroid-stimulating hormone TTR See Transthyretin Tuberculosis, 25, 36 TNF and, 93 Tuberculous arthritis, 248 Tuberculous osteomyelitis, 248 Tuberous xanthomas, 263 Tumor necrosis factor See TNF Tumor necrosis factor receptor (TNF-R), 35 decreased production of, 59 Type collagen, 225, 225f degradation of, 226 UC See Ulcerative colitis Ulcerative colitis (UC), 141, 163 familial aggregation of, 141 prevalence of, 141 Ulcers, chronic, 115 Ultrasonography, 220 Ultrasound, 221t Undifferentiated connective tissue disease, 119 Undifferentiated spondyloarthritis definition of, 140 diagnosis of, 140f management of, 141 UPEP See Urine protein electrophoresis Upper airway neoplasms, 150 Upregulation, of genes, 66 Urate-lowering therapy, 237 Uric, 286t Urinary uric acid levels, 219, 292t Urine analysis, 292t Urine protein electrophoresis (UPEP), 192 Urogenital lesions, 136 Uveitis See Acute anterior uveitis V sign, 198 Vagotomy, 266 van der Waals interactions, 48 Variable regions, 28 Vascular ectasia, 121 Vascular endothelial growth factor (VEGF), 110 Vascular endothelium, 47 Vascular granulation tissue, 85 Vascular occlusions, SLE and, 73 Vascular therapy, goal of, 120 350 Vasculitis, 69, 144, 214 See also Polyarteritis nodosa; specific types of vasculitis syndromes antibody development in, 146 approach to patient, 146–147, 147f associations with, 147 classification of, 144 clinical findings on, 147 connective tissue disorders and, 163 cryoprecipitates of, 145 definition of, 144 diagnosis of, 146 EBV and, 163 glucocorticoid therapies for, 163 HIV and, 163 malignancies associated with, 163 mimicry of, 146, 147t pathogenesis of, 144 pathogenic immune complex formation in, 144–145 pathophysiology of, 144 patient workup for, 146 of pulmonary artery, 167 radiographic findings on, 147 relapsing polychondritis and, 168t serum sickness and, 145 Sjögren’s syndrome and, 128f subacute bacterial endocarditis, 163 syndromes of, 145t tissue damage in, 145 treatment of, 147f, 163–164 toxic side effects of, 164t underlying primary diseases and, 163 vessel damage in, potential mechanisms of, 145t Vasculopathy, obliterative, 111 Vasoactive amines, 145 Vasospasm, 117 VEGF See Vascular endothelial growth factor Venous thromboembolic disease, 322 Ventricular dysfunction, 116 Very low-density lipoprotein (VLDL), 263 Index Vessel lumen damage, 145 Viral arthritis, 248–249 Viral infections, inflammatory myopathies and, 202 Viral proteins, DCs and, 17 Vitamins, 290t Vitiligo, 62t VLDL See Very low-density lipoprotein von Willebrand disease, 260 Waldenstrom’s macroglobulinemia, 191 Watermelon stomach, 117, 121 Weakness, due to muscle pain/tenderness, 203 Wegener’s granulomatosis, 42, 60t, 62t, 147 ANCA in, 145 antiproteinase-3 ANCA in, 150 biologic therapies for, 151–152 characterization of, 317 clinical manifestations of, 148–150 frequency of, 149t CT scan of, 148f definition of, 147 diagnosis of, 150 ear/nose/throat involvement in, 149t ESR rates in, 149–150 eye involvement in, 148–149, 149t as fatal, 150 follow up for, 151 glomerulonephritis and, 317 glucocorticoid therapies for, 150–151 toxic side effects of, 151 incidence of, 147 laboratory manifestations of,148–150 lung histology in, 148f MPA v., 321 organ-specific treatment for, 152 pathogenesis of, 147–148 pathology of, 147–148 peripheral blood mononuclear cells from, 148 presentation of, 317 Wegener’s granulomatosis (Cont.): prevalence of, 147 pulmonary involvement in, 148, 149t renal involvement in, 148–149, 149t skin lesions in, 149 Staphylococcus aureus in, 148 thrombocytosis in, 150 treatment of, 150–152, 320 trimethoprim-sulfamethoxazole for, 152 upper airway involvement in, 148 Whipple’s disease, 142–143 WHO See World Health Organization Women AS in, 131 fibromyalgia in, 254, 324 gonococcal arthritis in, 246 gout in, 236 Raynaud’s phenomenon in, 114 World Health Organization (WHO), 44 on ARF, 103, 104t WSXWS See Tryptophan-serineX-tryptophan-serine Xanthomas, 263 Xerostomia, 125, 126t treatment for, 127 X-linked form of severe combined immune deficiency syndrome (X-SCID), 21 X-linked hyper-IgM syndrome, 31 X-SCID See X-linked form of severe combined immune deficiency syndrome Yersinia, ReA and, 134, 136 Z deformity, 87 ... Services, Bethesda [3, 5, 17] JOHN J CUSH, MD Director of Clinical Rheumatology, Baylor Research Institute; Professor of Medicine and Rheumatology, Baylor University Medical Center, Dallas [17] ELYSE... the immunology and rheumatology chapters contained in Harrison’s Principles of Internal Medicine, sought to provide readers with a current view of the science and practice of rheumatology After... subspecialty of internal medicine With this edition of the Harrison’s Rheumatology, it remains our goal to provide the expertise of leaders in rheumatology and immunology to all students of medicine who