Gout and Other Crystal Arthropathies

372 Pages·2011·19.41 MB·English

by  Robert Terkeltaub

GOUT AND OTHER CRYSTAL
ARTHROPATHIES
Robert Terkeltaub, MD
Chief, Rheumatology Section
San Diego Veterans Affairs Medical Center;
Professor of Medicine, Interim Chief
Division of Rheumatology, Allergy and Immunology
University of California San Diego School of Medicine
La Jolla, California, USA
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
GOUT AND OTHER CRYSTAL ARTHROPATHIES, First edition ISBN: 978-1-4377-2864-4
Copyright © 2012 by Saunders, an imprint of Elsevier Inc.
All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, with-
out permission in writing from the publisher.
Notice
Knowledge and best practice in this field are constantly changing. As new research and experience broaden
our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Read-
ers 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 the practitioner, relying on
their own experience and knowledge of the patient, 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 Editors assumes any liability for any injury and/or damage to persons
or property arising out of or related to any use of the material contained in this book.
The Publisher
Library of Congress Cataloging-in-Publication Data
Gout and other crystal arthropathies / [edited by] Robert Terkeltaub.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4377-2864-4 (hardcover : alk. paper)
1. Gout. 2. Chondrocalcinosis. I. Terkeltaub, Robert.
[DNLM: 1. Gout. 2. Calcium Compounds--metabolism. 3.
Chondrocalcinosis. 4. Hyperuricemia. WE 350]
RC629.G683 2012
616.3′999--dc23 2011032013
Acquisitions Editor: Pamela Hetherington
Developmental Editor: Roxanne Halpine Ward
Publishing Services Manager: Peggy Fagen
Project Manager: Siva Raman Krishnamoorthy
Design Direction: Steven Stave
Printed in the United States of America
Last digit is the print number: 9 8 7 6 5 4 3 2 1
I dedicate this book to my patients, mentors, colleagues in the field, and students and research trainees, who
have inspired me and taught me so much about these disorders. I also dedicate the work to my wife Barbara,
whose support was integral to the success of this endeavor.
Acknowledgments
I am grateful to acknowledge Robyn Austin and Wendy Geolina, who provided administrative support
and editing assistance, as well as Pamela Hetherington for her strong vision and support, Roxanne Ward for
manuscript preparation, and Peggy Fagen and the production staff at Elsevier for their hard work in bringing
this book to print.
I dedicate this book to my patients, mentors, colleagues in the field, and students and research trainees, who
have inspired me and taught me so much about these disorders. I also dedicate the work to my wife Barbara,
whose support was integral to the success of this endeavor.
Acknowledgments
I am grateful to acknowledge Robyn Austin and Wendy Geolina, who provided administrative support
and editing assistance, as well as Pamela Hetherington for her strong vision and support, Roxanne Ward for
manuscript preparation, and Peggy Fagen and the production staff at Elsevier for their hard work in bringing
this book to print.

Contributors
Naohiko Anzai, MD, PhD Rebecca Grainger, BMedSci, PhD, Diego F. Lemos, MD
Professor and Chairman MBChB, FRACP Assistant Professor of Radiology
Department of Pharmacology and Toxicology Senior Lecturer Section Head Musculoskeletal Imaging
Dokkyo Medical University School of Medicine Department of Medicine Department of Radiology
Tochigi, Japan University of Otago Wellington Fletcher Allen Health Care and the University of
Consultant Rheumatologist Vermont
Joana Atxotegi Saenz de Buruaga, MD Wellington Regional Rheumatology Unit Burlington, Vermont, USA
Assistant Physician Hutt Valley District Health Board
Rheumatology Division Wellington, New Zeland Frédéric Lioté, MD, PhD
Hospital de Cruces Professor of Rheumatology
Vizcaya, Spain Pierre-André Guerne, MD Paris Diderot University
Professor of Internal Medicine President, Sorbonne Paris Cité
Hyon K. Choi, MD, DrPH and Rheumatology Deputy Head
Professor of Medicine Associate Medical Officer Centre Viggo Petersen, Service de Rhumatologie
Section of Rheumatology and the Clinical Division of Rheumatology (Pôle Appareil Locomoteur)
Epidemiology Unit University Hospitals of Geneva Hôpital Lariboisière (Assistance Publique-
Boston University school of Medicine Geneva, Switzerland Hôpitaux de Paris)
Boston, Massachusetts, USA Paris, France
Ana Maria Herrero-Beites, MD
Nicola Dalbeth, MBChB, MD, FRACP Senior Assistant Ru Liu-Bryan, PhD
Associate Professor and Rheumatologist Rehabilitation Division Associate Professor of Medicine
Department of Medicine, Faculty of Medical and Hospital de Górliz University of California San Diego
Health Sciences Vizcaya, Spain San Diego, California, USA
University of Auckland
Auckland, New Zealand Tudor H. Hughes, MD, FRCR Paul MacMullan, BComm, BSc
Professor of Clinical Radiology (Physio), MBChB, BAO
Hitoshi Endou, MD, PhD Radiology Resident Program Director Research Fellow
Professor Emeritus Vice Chair of Education Department of Molecular and Cellular
Department of Pharmacology and Toxicology Department of Radiology Therapeutics
Kyorin University School of Medicine University of California at San Diego Royal College of Surgeons in Ireland
Tokyo, Japan San Diego, California, USA Rheumatology Department
Mater Misericordiae University Hospital
Angelo L. Gaffo, MD, MSPH Dinesh Khanna, MD, MSc Dublin, Ireland
Assistant Professor of Medicine Associate Professor of Medicine
Division of Rheumatology Marvin and Betty Danto Research Professor Elisabeth Matson, DO
University of Alabama at Birmingham Director Rheumatology Fellow
Staff Rheumatologist University of Michigan Scleroderma Program Division of Rheumatology
Birmingham VA Medical Center Division of Rheumatology The Warren Alpert Medical School at Brown
Birmingham, Alabama, USA Department of Internal Medicine University
University of Michigan School of Medicine Providence, Rhode Island, USA
Amilcare Gentili, MD Ann Arbor, Michigan, USA
Professor of Clinical Radiology Geraldine M. McCarthy, MD
Department of Radiology Puja Khanna, MD, MPH Consultant Rheumatologist
University of California San Diego Assistant Professor Department of Medicine
Chief, Radiology Service Division of Rheumatology Mater Misericordiae University Hospital
San Diego VA Health Care System Department of Internal Medicine Clinical Professor of Medicine
San Diego, California, USA University of Michigan School of Medicine UCD School of Medicine
Ann Arbor, Michigan, USA and Medical Science
University of College Dublin
Eswar Krishnan, MD, MPhil Honorary Associate Professor
Assistant Professor of Medicine Molecular and Cellular Therapeutics
Stanford University Royal College of Surgeons in Ireland
Stanford, California, USA Dublin, Ireland
vii
viii Contributors
Gillian McMahon, BSc, PhD, MRSC, Supriya G. Reddy, MPH Francisca Sivera, MD
CChem, FICI Program Administrator Consultant in Rheumatology
Analytical Chemistry Lecturer Clinical Immunology and Rheumatology Rheumatology Unit
School of Chemical Sciences University of Alabama Hospital del Vinalopó
Dublin City University at Birmingham Clinical Assistant Professor
Dublin, Ireland Birmingham, Alabama, USA Department of Internal Medicine
Doctoral Student (PhD candidate) ( Rheumatology)
Tuhina Neogi, MD, PhD, FRCPC Department of Health Science Universidad Miguel Hernandez
Associate Professor of Medicine The University of Alabama Alicante, Spain
Sections of Clinical Epidemiology Research Tuscaloosa, Alabama, USA
and Training Unit and Rheumatology Lisa K. Stamp, MBChB, FRACP, PhD
Department of Medicine Anthony M. Reginato, PhD, MD Associate Professor
Boston University School of Medicine Director, Rheumatology Research Department of Medicine
Associate Professor of Epidemiology and Musculoskeletal Ultrasound University of Otago Christchurch
Department of Epidemiology Division of Rheumatology Rheumatologist
Boston University School of Public Health University of Medicine Foundation Department of Rheumatology, Immunology
Boston, Massachusetts, USA Rhode Island Hospital and Allergy
The Warren Alpert School of Medicine Christchurch Hospital
George Nuki, MB, FRCP at Brown University Christchurch, New Zealand
Emeritus Professor of Rheumatology Staff Physician
Rheumatic Diseases Unit Medical Service/Rheumatology William J. Taylor, PhD, MBChB,
Western General Hospital Providence VA Medical Center FRACP, FAFRM
Emeritus Professor of Rheumatology Providence, Rhode Island, USA Associate Professor and Head of Unit
Osteoarticular Research Group Rehabilitation Teaching and Research Unit
Institute of Genetics and Molecular Medicine Philip L. Riches, BSc, MRCP Department of Medicine
University of Edinburgh Consultant Rheumatologist University of Otago Wellington
Edinburgh, Scotland, UK Rheumatic Diseases Unit Rheumatologist and Rehabilitation Physician
Western General Hospital Wellington Regional Rheumatology Unit
Eliseo Pascual, MD, PhD Honorary Senior Lecturer Hutt Valley District Health Board
Professor of Medicine Institute of Genetics and Molecular Medicine Wellington, New Zealand
Universidad Miguel Hernández University of Edinburgh
Head, Rheumatology Section Edinburgh, Scotland, UK Robert Terkeltaub, MD
Hospital General Universitario de Alicante Chief, Rheumatology Section
Alicante, Spain Naomi Schlesinger, MD San Diego Veterans Affairs Medical Center
Professor of Medicine Professor of Medicine, Interim Chief
Fernando Perez-Ruiz, MD, PhD Chief, Division of Rheumatology Division of Rheumatology, Allergy,
Specialist Faculty Department of Medicine and Immunology
Rheumatology Division Robert Wood Johnson Medical School University of California San Diego School
Hospital de Cruces University of Medicine and Dentistry of Medicine
Vizcaya, Spain of New Jersey La Jolla, California, USA
New Brunswick, New Jersey, USA
Kenneth P.H. Pritzker, MD, FRCPC Ralf G. Thiele, MD, FACR
Professor, Laboratory Medicine Jasvinder A. Singh, MBBS, MPH Assistant Professor of Medicine
and Pathobiology; Surgery Staff Physician Department of Medicine
University of Toronto Medicine Service and Center for Surgical Allergy/Immunology & Rheumatology Division
Pathologist Medical Acute Care Research University of Rochester School of Medicine
Mount Sinai Hospital and Transitions and Dentistry
Toronto, Ontario, Canada Birmingham VA Medical Center; Rochester, New York, USA
Associate Professor of Medicine
Juan Garcia Puig, MD, PhD and Epidemiology Rosa J. Torres, MD, PhD
Associate Professor Department of Medicine Biomedical Researcher
Division of Internal Medicine Division of Rheumatology Biochemistry Laboratory, Metabolic Vascular
Metabolic and Vascular Unit University of Alabama at Birmingham Unit, Idipaz
Hospital Universitario La Paz, IdiPAZ Birmingham, Alabama, USA La Paz University Hospital
Universidad Autónoma Research Collaborator Madrid, Spain
Madrid, Spain Department of Orthopedic Surgery
Mayo Clinic Collage of Medicine
Rochester, Minnesota, USA
Foreword
Gouty arthritis was among the earliest of diseases to be rec- community-based epidemiologic studies have demonstrated
ognized as a clinical entity; there is a description of gout in an age-related radiographic prevalence of chondrocalcino-
ancient Egypt in the second millennium bc attributable to sis of approximately 10% in persons in the seventh decade
Imhotep (the “Father of Medicine”). However, the role of of life. CPPD deposition in the form of chondrocalcinosis is
crystals of monosodium urate (MSU) in the pathogenesis of positively associated with osteoarthritis (OA) but is also seen
gout and recognition of other crystal-associated deposition in the absence of OA and variably influences progression of
arthropathies emerged much later. Drawings of crystals taken articular cartilage loss in patients with knee OA. Basic cal-
from a tophus from a patient with gout were made by the pio- cium phosphate (BCP) crystals are also frequently associated
neer Dutch microscopist Antoni Van Leeuwenhoek in 1769, with OA as well as with age-related calcific periarthritis and
although he was unaware that they were crystals and ignorant a destructive form of age-related, apatite-associated arthritis.
of their chemical composition. A century later, the English Fifty years ago, gout became a paradigm for understanding,
chemist Wollaston was able to show that a gouty tophus from treating, and preventing a chronic rheumatic disease after the
his own ear was composed of sodium urate, following chemi- development of allopurinol as an effective uricostatic drug. A
cal identification of uric acid in urinary calculi by the Swed- decade later, Seegmiller’s discovery that primary purine over-
ish apothecary Scheele in 1776. Elevated levels of uric acid in production and severe premature gout in boys with Lesch-
the serum of patients with gout were first demonstrated by Nyhan syndrome resulted from an inherited deficiency of the
Sir Alfred Baring Garrod in 1848 using a semiquantitative purine salvage enzyme hypoxanthine guanine phosphoribo-
“thread test”—an early milestone in the development of the syltransferase led to an explosion of knowledge and scientific
discipline of clinical chemistry. literature about the regulation of purine metabolism that was
In a set of remarkably prescient propositions published in characterized as the “purine revolution.” Much of this was
1859 in his book A Treatise on Gout and Rheumatic Gout, A. included in a comprehensive monograph, Gout and Hyperurice-
B. Garrod was the first to show a clear understanding of the mia, by Wyngaarden and Kelley published in 1976, and evolving
importance of hyperuricemia and the pivotal role of urate crys- knowledge of calcium crystal deposition and disease, which was
tals in the pathogenesis of gout. At the turn of the nineteenth slower to develop, was included in a shorter monograph, Crys-
century, Freudweiler demonstrated that intra-articular injec- tals and Joint Disease, by Dieppe and Calvert published in 1986.
tions of crystals of sodium urate could mimic acute attacks of Following the introduction and use of allopurinol 40 years
gout and showed that subcutaneous injections of microcrystals ago, a widespread perception developed that gout was no lon-
were followed by the development of tophus-like lesions. The ger a clinical problem. For many years, gout has been largely
historical importance of these experiments only came to light, managed in general practice and has ceased to be at the fore-
however, in the early 1960s after rediscovery of the capacity of front of interest for rheumatologists and clinical investigators.
microcrystals of sodium urate to induce inflammation in joints, Recent studies have, however, shown that this potentially cur-
skin, and subcutaneous tissues by Faires and McCarty and by able condition is being inadequately treated and that the inci-
Seegmiller and his colleagues. These experiments followed dence and prevalence of gout have doubled over the past 30
publication of McCarty and Hollander’s seminal paper demon- years. Gout is now the most common inflammatory joint dis-
strating the diagnostic value of detecting negatively birefringent ease in men and an increasingly frequent cause of inflamma-
crystals of MSU, by polarizing light microscopy, within syno- tory joint disease in postmenopausal women. The changing
vial fluid leukocytes during acute attacks of gouty arthritis, and epidemiology of gout is largely attributable to rising levels of
a series of landmark publications demonstrating the presence serum urate, associated with the changing age structure of the
of positively birefringent microcrystals, which were confirmed population, as well as with the worldwide epidemic of obe-
by x-ray diffraction to be calcium pyrophosphate dihydrate sity and a dramatic increase in the prevalence of the metabolic
(CPPD) in patients with acute synovitis and “pseudogout.” syndrome. Additional risk factors include the use of diuret-
Although experiments demonstrating that acute synovitis ics, consumption of alcoholic beverages (especially beer),
could also be induced by injections of microcrystals of CPPD diets containing increased quantities of red meat or shellfish
into normal canine and human joints appeared to confirm a purines, and heavy consumption of fructose-sweetened soft
pathogenic role for CPPD crystals in patients with pseudo- drinks. Complicated gout associated with comorbidities such
gout, the extent to which deposition of CPPD crystals are the as hypertension and cardiovascular and renal disease is also
cause, or the consequence, of other pathology in the wide an increasing problem. Overt tophi are now seen in 30% of
range of clinical settings subsequently described and classi- untreated patients within 5 years of the first acute attack.
fied by McCarty as manifestations of CPPD deposition dis- Developments in imaging with ultrasound, computed tomog-
ease remains much less certain. Cadaver studies undertaken raphy, and magnetic resonance imaging are also revealing
more than 80 years ago had shown that meniscus calcifica- more widespread evidence of crystal deposition in patients
tion in the knee was a frequent age-related finding, and recent with gout much earlier in the course of the disease.
ix