DK9382_half 2/15/06 9:43 AM Page 1 Crystal-Induced Arthropathies Crystal-Induced Arthropathies Gout, Pseudogout and Apatite-Associated Syndromes edited by Robert L. Wortmann University of Oklahoma College of Medicine Tulsa, Oklahoma, U.S.A. H. Ralph Schumacher, Jr. University of Pennsylvania and VA Medical Center Philadelphia, Pennsylvania, U.S.A. Michael A. Becker University of Chicago School of Medicine Chicago, Illinois, U.S.A. Lawrence M. Ryan Medical College of Wisconsin Milwaukee, Wisconsin, U.S.A. New York London Taylor & Francis is an imprint of the Taylor & Francis Group, an informa business DK9382_Discl.fm Page 1 Friday, April 14, 2006 11:40 AM Published in 2006 by Taylor & Francis Group 270 Madison Avenue New York, NY 10016 © 2006 by Taylor & Francis Group, LLC No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-10: 0-8493-9382-5 (Hardcover) International Standard Book Number-13: 978-0-8493-9382-2 (Hardcover) Library of Congress Card Number 2006040382 This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. 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Library of Congress Cataloging-in-Publication Data Crystal-induced arthropathies : gout, pseudogout and apatite-associated syndromes / edited by Robert L. Wortmann … [et al.] p. cm. ISBN-13: 978-0-8493-9382-2 (alk. paper) ISBN-10: 0-8493-9382-5 (alk. paper) 1. Gout--Etiology. 2.Hyperuricemia. I. Wortmann, Robert. RC629.3.C795 2006 616.3’999--dc22 2006040382 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com Taylor & Francis Group is the Academic Division of Informa plc. Preface When most people hear the term “crystal-induced arthropathy,” they think of gout, the disease that results from the body’s response to monosodium urate crystals. Furthermore, they usually envision a patient with acute, intensely inflammatory monoarthritis, the cardinal feature of gout. However, gout is not the most common crystal-induced arthropathy. The arthropathies that result from the body’s response to calcium-containing crystals, those of calcium pyrophos- phate dihydrate or basic calcium phosphates, occur more frequently. In fact, it is likely that everyone will develop some sort of calcium-containing arthropathy if they live long enough. Furthermore, although each crystal type can induce an acute monoarticular disease, each can also be associated with a variety of other clinical presentations. Thus, the crystal-induced arthropathies are common and complex diseases. Whereas gout has been recognized for centuries, not until 1960 was it appreciated that monosodium urate crystals were present in the synovial fluid in patients with attacks of gout. It was at that same time that calcium pyrophosphate dihydrate crystals were identified in joint fluids from patients who were pre- viously believed to suffer from gout and the term “pseudogout” was coined. Our present understanding of basic calcium phosphate arthropathies began to unfold in the early 1980s with the description of Milwaukee shoulder syndrome. Motivation for this work stemmed from the editors’ long-standing interest in the crystal-induced arthropathies, each of us having been actively investigating various elements of these diseases for the last 30 to 40 years. It was our desire to produce a concise but comprehensive review of this large field, recognizing that much of the present understanding of these diseases is the result of observations that have occurred during the span of our careers. In addition to reviewing the present state of understanding regarding the clinical presentations of the various iii iv Preface diseases, their respective underlying pathogeneses, and current approaches to management, our goals included providing a sound basis for understanding the discoveries that will be made in the future, both in etiology and in therapy. If we have accomplished our goals, this book will be helpful to clinicians, teachers, and scientists. The authors who have contributed to this text share the editors’ interest and enthusiasm for the field. We were particularly pleased that Dan McCarty was willing to share his perspective on the history of the crystal-induced arthro- pathies. As one of the individuals who identified monosodium urate crystals in gouty synovial fluids, recognized pseudogout, and described Milwaukee shoulder syndrome, he has contributed greatly to our knowledge of the field. In addition, he has provided training and influenced a large number of investigators, many of whom authored chapters for this edition. Although most authors of this text can not match Dr. McCarty’s breadth of observations, each of the senior authors has been involved in original research in the area about which they wrote and is widely recognized for their individual expertise. We are also pleased to have involved younger individuals who will become future leaders in this field. Robert L. Wortmann H. Ralph Schumacher, Jr. Michael A. Becker Lawrence M. Ryan Contents Preface ....iii Contributors ....xiii 1. Crystal-Induced Arthropathies—Historical Aspects . 1 Daniel J. McCarty Introduction . 1 Monosodium Urate Crystal Deposition . 1 Calcium Pyrophosphate Dihydrate (CPPD) Crystal Deposition . 3 Basic Calcium Phosphate Crystal Deposition . 4 References . 5 2. The Epidemiology of Gout and Calcium Pyrophosphate Dihydrate Deposition Disease . 7 Kenneth G. Saag, Ted R. Mikuls, and Joel Abbott Introduction—Gout . 7 Estimates of Frequency of Gout . 9 Gout Comorbidities, Other Associations, and Prognosis .... 18 Calcium Pyrophosphate Dihydrate Deposition Disease . 22 Estimates of Frequency of CPPD Diseases . 22 Epidemiology of Basic Calcium Phosphate Arthropathies . 26 References . 27 v vi Contents 3. Genetics of the Crystal-Induced Arthropathies . 37 Raihana Zaka and Charlene J. Williams Introduction . 37 Familial Gout Syndromes . 37 Familial Juvenile Hyperuricemic Nephropathy . 38 Autosomal Dominant Medullary Cystic Kidney Disease . 40 Candidate Genes for FJHN and ADMCKD1 and 2 . 41 Genetic Heterogeneity in FJHN . 42 Treatment of the Hyperuricemic Nephropathies . 43 Other Genetic Studies of Gout . 44 Familial Calcium Pyrophosphate Dihydrate (CPPD) Deposition Disease . 44 Genetic Linkage Analyses in Familial CPPD Disease . 46 Candidate Genes for Familial CPPD Diseases . 46 Genetic Heterogeneity in Familial CPPD Disease . 48 Ank and CPPD Deposition Disease . 48 Familial Conditions Involving Basic Calcium Phosphate (Apatite) Crystals . 50 Analyses of Genetic Linkage and Candidate Genes in Familial Basic Calcium Phosphate Arthropathies . 51 Conclusions . 51 References . 52 4. Gout: Presentation, Natural History, and Associated Conditions . 61 N. Lawrence Edwards Introduction . 61 Stages of Classic Gout . 61 Less Classic Presentations of Gout . 68 Clinical Associates of Gout . 72 References . 76 5. Asymptomatic Hyperuricemia . 81 John Kanellis, Duk-Hee Kang, Daniel I. Feig, and Richard J. Johnson Introduction . 81 Uric Acid: Biochemistry . 82 The Uricase Gene is Mutated in Humans and in Other Hominoids . 83 Hyperuricemia in Humans: A Definition . 83 Hyperuricemia and the Risk of Gouty Arthritis, Calculi, and Nephropathy . 84 Contents vii Dietary and Physiological Factors that can Influence Serum Urate Levels . 85 Hyperuricemia is Associated with Hypertension, Vascular Disease, and the “Metabolic Syndrome” . 86 The Prognostic Significance of Serum Urate Levels . 87 Uric Acid: Beneficial or Harmful? . 88 Urate May Be a Useful Biomarker . 88 Urate and Endothelial Dysfunction . 89 Effects of Urate on Vascular Smooth Muscle . 90 Animal Models of Hyperuricemia . 91 Should Asymptomatic Hyperuricemia be Treated? . 92 Further Reading . 93 References . 93 6. Pseudogout: Presentation, Natural History, and Associated Conditions . 99 Ann K. Rosenthal Introduction . 99 Epidemiology . 100 Clinical Presentation . 101 Diagnosis . 104 Classification of CPPD Deposition Disease . 106 Conclusions . 111 References . 112 7. Clinical Manifestations of Basic Calcium Phosphate (Apatite) Deposition Disease . 117 Kanyakorn Jaovisidha and Lawrence M. Ryan Introduction . 117 Sporadic or Idiopathic BCP Crystal Deposition Disease . 117 Hereditary BCP Crystal Disease . 123 Systemic Diseases Associated with BCP Crystal Deposition . 126 Drug-Related