Don’t Forget Your Online Access to Mobile. Searchable. Expandable. ACCESS it on any Internet-ready device SEARCH all Expert Consult titles you own LINK to PubMed abstracts ALREADY REGISTERED? FIRST-TIME USER? 1. Log in at expertconsult.com 1. REGISTER 2. Scratch off your Activation Code below • Click “Register Now” at expertconsult.com 3. Enter it into the “Add a Title” box • Fill in your user information and click “Continue” 4. Click “Activate Now” 2. ACTIVATE YOUR BOOK 5. Click the title under “My Titles” • Scratch off your Activation Code below • Enter it into the “Enter Activation Code” box • Click “Activate Now” • Click the title under “My Titles” For technical assistance: Activation Code email [email protected] call 800-401-9962 (inside the US) call +1-314-995-3200 (outside the US) KELLEY’S Textbook of Rheumatology This page intentionally left blank VOLUME I KELLEY’S Textbook of Rheumatology NINTH EDITION Gary S. Firestein, MD Professor of Medicine Dean and Associate Vice Chancellor of Translational Medicine UC San Diego Health Sciences La Jolla, California Ralph C. Budd, MD Professor of Medicine Director, Vermont Center for Immunology and Infectious Diseases The University of Vermont College of Medicine Burlington, Vermont Sherine E. Gabriel, MD, MSc William J. and Charles H. Mayo Professor Professor of Medicine and Epidemiology Mayo Clinic College of Medicine Rochester, Minnesota Iain B. McInnes, PhD, FRCP, FRSE Muirhead Professor of Medicine Director, Institute of Infection, Immunity and Inflammation College of Medical, Veterinary and Life Sciences University of Glasgow Glasgow, United Kingdom James R. O’Dell, MD Bruce Professor of Medicine Vice Chairman, Department of Internal Medicine University of Nebraska College of Medicine; Chief, Division of Rheumatology and Immunology University of Nebraska Medical Center; Omaha VA Omaha, Nebraska 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 KELLEY’S TEXTBOOK OF RHEUMATOLOGY, NINTH EDITION ISBN: 978-1-4377-1738-9 Copyright © 2013, 2009, 2005, 2001, 1997, 1993, 1989, 1985, 1981 by Saunders, an imprint of Elsevier Inc. Mayo drawings © Mayo Foundation for Medical Education and Research. Cover image: Courtesy Thomas Deerinck and Mark Ellisman, the National Center for Microscopy and Imaging Research, UCSD. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data Kelley’s textbook of rheumatology / Gary S. Firestein … [et al.].—9th ed. p. ; cm. Textbook of rheumatology Includes bibliographical references and index. ISBN 978-1-4377-1738-9 (hardcover : alk. paper) I. Firestein, Gary S. II. Kelley, William N., 1939- III. Title: Textbook of rheumatology. [DNLM: 1. Rheumatic Diseases. 2. Collagen Diseases. 3. Joint Diseases. 4. Lupus Erythematosus, Systemic. WE 544] 616.7′23—dc23 2011036500 Executive Content Strategists: Pamela Hetherington and Michael Houston Senior Content Development Specialist: Janice Gaillard Publishing Services Manager: Patricia Tannian Working together to grow Senior Project Manager: Kristine Feeherty Design Direction: Ellen Zanolle libraries in developing countries Printed in China www.elsevier.com | www.bookaid.org | www.sabre.org Last digit is the print number: 9 8 7 6 5 4 3 2 1 Sincerest thanks to my wonderful wife, Linda, and our children, David and Cathy, for their patience and support. Also, the editorial help of our three Cavalier King Charles puppies, Winston, Humphrey, and Punkin, was invaluable. Gary S. Firestein Sincere thanks for the kind mentoring from Edward D. Harris, Jr., as well as for the support of my wife, Lenore, and my children, Graham and Laura. Ralph C. Budd To my three boys: my dear husband, Frank Cockerill, and our two wonderful sons, Richard and Matthew, for being my constant source of inspiration, love, and pride. And to my parents, Huda and Ezzat, for their love and tireless support. Sherine E. Gabriel To my wife, Karin, for her patience, understanding, and love and to our wonderful girls, Megan and Rebecca, who continue to enlighten me. Iain B. McInnes Sincere thanks to my wife, Deb, for her patience and love and to our wonderful children, Kim and Andy, Jennie and Dan, and Scott and Melissa. I also want to thank the members of my division who continue to support me in all my efforts. James R. O’Dell This page intentionally left blank DEDICATION Rutgers Medical School recruited Ted to become Chair of Medicine, and four years later he assumed the Chair of Medicine position at Stanford, a position he held until 1995. During Ted’s career he authored well over 100 peer- reviewed publications and 70 reviews, chapters, editorials, and books. Ted served as President of the American College of Rheumatology (ACR) and, during his tenure, skillfully helped arrange an amicable separation of the ACR and the Arthritis Foundation so that each organization could better pursue its mission. He was named a fellow of the British Royal College of Physicians in 2002 and received the Presi- dential Gold Medal from ACR in 2007. Ted had a remarkably perceptive intellect and a razor wit. A former English major, his writing was crisp and vigorous. His love of language elevated and animated text. Colleagues knew that an “EDH note” could be mellifluous, mirthful, Edward D. Harris, Jr., MD and merciless all at once. As academic secretary to Stanford, 1937-2010 Ted’s amusing touches to the minutes of the Stanford Senate were legendary. He might squeeze in a quote from Dr. Seuss’s Horton Hatches the Egg, add footnotes on faculty members’ Edward D. “Ted” Harris, Jr., was one of the four founding attire, or slip in sly editorial comments such as “wisely inter- editors of the Textbook of Rheumatology. In the late 1970s, rupted” or “introduced with appreciated brevity.” As a Bill Kelley sensed the need for a text that reflected the result, Ted’s words resonated and got results. growth of rheumatology into a mature discipline. He met The English degree came in handy when, in 1997, Ted with Ted, who quickly agreed, and they identified Shaun was named executive secretary of Alpha Omega Alpha Ruddy and Clem Sledge as co-editors. A prime concern was (AOA) and editor of The Pharos, the society’s nontechnical that the new book should be grounded in the abundant compendium of essays, poetry, art, and articles on medical information in basic science that supported our subspecialty. history, ethics, and health policy. Ted breathed new life and The standards they set were responsible for the high style into the journal during his 13-year tenure as editor. quality of the finished Textbook. Ted’s choice of the iconic Ted also created a 532-page anthology called Creative profile of Renoir, who suffered from rheumatoid arthritis, Healers: A Collection of Essays, Reviews, and Poems from The has graced the cover of nine editions of the book and Pharos, 1938-1998, published by AOA in 2004. Reviewers served to connect us to the humanitarian aspect of our on Amazon.com have mentioned the editor’s keen eye for discipline. engaging writing, calling the volume’s contents “moving” Ted was a graduate of Dartmouth College and its medical and “a tribute to the range of interests percolating around school and of Harvard Medical School. Following his resi- in active intellects.” dency at Massachusetts General Hospital he moved to the Ted Harris mentored a generation of rheumatologists and National Institutes of Health (NIH), where he engaged in taught us all by his example of dynamic creative thought research on collagen. In his spare moments he also formed and a deep humanitarian spirit. All of us involved with a jazz ensemble, with himself playing bass. Upon Ted’s Kelley’s Textbook of Rheumatology feel a profound sadness return to Mass General he entered a rheumatology fellow- with the loss of Ted, but even here Ted would provide the ship and joined the laboratory of Dr. Stephen Krane, where appropriate perspective, with a passage he wrote in a Pharos Ted applied his knowledge of collagen to the inflammatory editorial: “Melancholy, that gray veil that takes color out of synovium of rheumatoid arthritis. life, can, at the same time, add to the brilliance and value In 1970 Ted was recruited back to Dartmouth, where he of life, if we feel what it is asking of us. Melancholy and built a robust connective tissue disease unit and received sadness, similar to love, can make those compartment walls one of the NIH’s first arthritis center awards. Along with in our minds permeable, enabling us to express empathy long-time colleague Dr. Constance Brinckerhoff, Ted’s that is truly felt within.’’ group defined the role of collagenase and metalloproteinases Ted Harris was a consummate scholar and a great human- in the rheumatoid synovium. In 1979 Ted was sole author itarian, with a facile mind that spanned a wide array of of the seminal monograph Rheumatoid Arthritis, which interests from science to the arts. He was in essence a civi- detailed the complex interactions of the immune system lized man, something that has always been distinguished by with connective tissue in rheumatoid arthritis. In 1983 its rarity. vii This page intentionally left blank