Gout David S. Newcombe Gout Basic Science and Clinical Practice Edited by Dwight R. Robinson Author Editor David S. Newcombe, M.D. Dwight R. Robinson, M.D. Weston Department of Rheumatology Massachusetts Massachusetts General Hospital USA Boston USA ISBN 978-1-4471-4263-8 ISBN 978-1-4471-4264-5 (eBook) DOI 10.1007/978-1-4471-4264-5 Springer London Heidelberg New York Dordrecht Library of Congress Control Number: 2012950015 © Springer-Verlag London 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speci fi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro fi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. 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While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) This book is dedicated to Dr. Newcombe’s daughters: Catherine L. Newcombe, Kirsten N. Shilling and Sarah N. Faucett. Preface One might ask why a book devoted to a single disorder like gout is necessary since standard textbooks adequately review the usual clinical fi ndings and management of this disorder. The answer to that question is multifaceted. Gout is now clearly associated with several different clinical presentations that are often not described in detail in modern textbooks. Familial juvenile hyperuricemic nephropathy, autosomal dominant polycystic kidney disease, glycogen storage disease, and other disorders associated with hyperuricemia and gout are dysfunctions that need to be recognized early to avoid serious consequences. These and other clinical subsets of gout, in some cases, have also been de fi ned at the molecular level. Such advances in molecular biology provide another rationale for amplifying a physician’s knowledge of gout and the mechanisms of in fl ammation associated with this disease. Furthermore, the in fl ammatory and anti-in fl ammatory mediators, their mechanisms of action, and their real and putative roles in gout have recently been elucidated in greater detail and contribute to a better understanding of the pathogenesis of gout. Such new discoveries also provide a perspective on the capacity of the host to generate natural anti-in fl ammatory molecules, and such data may lead to new therapeutic initiatives. Uric acid, the precursor of gout, has also begun to attain more signi fi cance in relation to renal disease, hypertension, and obesity, and these interrelationships have been characterized in specialty journals but are not linked to textbook discussions of hyperuricemia and gout. These fi ndings alert the physician to evaluate uric acid associated disorders such as hypertension and obesity more extensively than has been the custom previously. Perhaps of greatest signi fi cance to the subjects of hyperuricemia and gout are the epidemiological studies showing that fewer than 10% of patients with gout are referred to rheumatologists. This circumstance leads to multiple errors in the management of this disease by physicians as well as patients. For example, the literature clearly documents the misuse of allopurinol since a number of patients are prescribed this agent for inappropriate reasons. Treating asymptomatic hyperuricemia with allopurinol in the absence of a sound rationale for the reduction in uric acid levels places patients at risk for the serious side effects of this agent including renal failure and even death. In addition, allopurinol has also been used as the sole agent for the treatment of acute gouty arthritis in elderly patients suffering from diuretic-induced gout as well as in other inappropriate settings where allopurinol is not indicated. Although uric acid is often the precursor of acute gouty arthritis, allopurinol vii viii Preface has no role in the management of acute gouty arthritis since it has no effect on an acute in fl ammatory response. Patients with hand deformities due to extensive tophaceous deposits may often be mistakenly diagnosed as rheu- matoid arthritis, and the need for the reduction of tophaceous deposits com- pletely ignored. Neglecting the treatment of chronic tophaceous gout may have serious consequences such as the collapse of a urate-laden vertebra or aseptic necrosis of the hip. Another important aspect of gout in modern times is the increasing identi fic ation of genetic dysfunctions associated with hyperuricemia and gout. Thus, a family history becomes a critical part of the evaluation of the hyperuricemic patient and avoids the pitfalls related to a delay in the early detection and treatment of affected family members. Often a cooperative patient who researches the family for underlying disorders may provide the physician with a most rewarding experience and be most useful in the early treatment of family members. The contents of this monograph provide the practicing physician with a ready source of information concerning hyperuricemia and gout as well as discussions of the management goals for the optimal treatment of these disorders. About the Author David Sugden Newcombe, M.D., graduated from Amherst College in 1952, cum laude in Biology. He received his medical degree from McGill University in 1956. Dr. Newcombe did his postdoctoral training at Boston City Hospital, Duke University, Boston University, and the Peter Brent Brigham Hospital at Harvard. He completed his military service in Korea in 1958. From 1965 to 1967, he was an Assistant Professor of Medicine at the University of Virginia. He then served as an Associate Professor of Medicine at the University of Vermont where he subsequently became the Director of Rheumatology. In 1977, he went to The Johns Hopkins University where he rose to the rank of Professor of Environmental Health Science in the University’s School of Hygiene and Public Health and held a Joint Appointment in the Department of Medicine in the University’s School of Medicine. Upon retiring from Johns Hopkins in 1992, he moved to Massachusetts where he was Associate Chief of Staff at the Bedford Veterans Administration Hospital until 1999. He then served as an Associate Physician at the Federal Medical Center (Devens) Massachusetts until he retired in 2001. Dr. Newcombe wrote two books: Inherited Biochemical Disorders and Uric Acid Metabolism (1975 University Park Press) and Clinical Immunotoxicology (1992 Raven Press). He also authored over one hundred medical and scientifi c articles. At the time of his retirement, Dr. Newcombe began the project that eventu- ally became this book on gout. He had a life-long interest in the disease and its complexities. The 1,000 page manuscript was completed just fi ve days before his death. Almost a year later his family requested that Dr. Robinson arrange for the publication of his work. The manuscript was then modi fi ed and updated. At this time the book represents the most comprehensive publi- cation available on gout, which is the world’s most common in fl ammatory rheumatic disease. The Editor, Dwight R. Robinson, M.D., is a rheumatologist at the Massachusetts General Hospital and Professor of Medicine, Harvard Medical School. ix