Title Page

Harrison’s Manual of Medicine, 20th Edition
Copyright © 2020 by McGraw Hill Inc. All rights reserved.
Editors
Contributors
Preface
Acknowledgments
Notices and Disclaimers
Unbound™ mobile platform © 2000-2020 Unbound Medicine, Inc. All rights reserved.

Editors

J. Larry Jameson, MD, PhD
Robert G. Dunlop Professor of Medicine
Dean, Raymond and Ruth Perelman School of Medicine
Executive Vice President, University of Pennsylvania for the Health System
Philadelphia, Pennsylvania

Anthony S. Fauci, MD
Chief, Laboratory of Immunoregulation
Director, National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, Maryland

Dennis L. Kasper, MD
William Ellery Channing Professor of Medicine
Professor of Immunology
Department of Immunology
Harvard Medical School
Boston, Massachusetts

Stephen L. Hauser, MD
Robert A. Fishman Distinguished Professor
Department of Neurology
Director, UCSF Weill Institute for Neurosciences
University of California, San Francisco
San Francisco, California

Dan L. Longo, MD
Professor of Medicine
Harvard Medical School
Senior Physician, Brigham and Women’s Hospital
Deputy Editor, New England Journal of Medicine
Boston, Massachusetts

Joseph Loscalzo, MD, PhD
Hersey Professor of the Theory and Practice of Medicine,
Harvard Medical School
Chairman, Department of Medicine
Physician-in-Chief, Brigham and Women’s Hospital
Boston, Massachusetts

Contributors

ASSOCIATE EDITORS

S. ANDREW JOSEPHSON, MD
Professor and Chair, Department of Neurology, University of California,
San Francisco, San Francisco, California

CAROL A. LANGFORD, MD, MHS
Harold C. Schott Endowed Chair; Director, Center for Vasculitis Care and Research,
Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio

LEONARD S. LILLY, MD
Professor of Medicine, Harvard Medical School; Chief, Brigham and Women’s/
Faulkner Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts

DAVID B. MOUNT, MD
Assistant Professor of Medicine, Harvard Medical School; Renal Division, Brigham
and Women’s Hospital, Renal Division, Boston VA Healthcare System, Boston, Massachusetts

EDWIN K. SILVERMAN, MD, PhD
Professor of Medicine, Harvard Medical School; Chief, Channing Division of
Network Medicine, Department of Medicine, Brigham and Women’s Hospital,
Boston, Massachusetts

NEERAJ K. SURANA, MD, PhD
Assistant Professor in Pediatrics, Molecular Genetics and Microbiology, and
Immunology, Duke University School of Medicine, Durham, North Carolina

Numbers indicate the chapters written or co-written by the contributor.

ANTHONY S. FAUCI, MD
Chief, Laboratory of Immunoregulation; Director, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, Maryland
28, 44, 45, 49, 60, 61, 107, 153–170

GREGORY K. FOLKERS, MPH
Chief of Staff, Office of the Director, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, Maryland
107, 165

STEPHEN L. HAUSER, MD
Robert A. Fishman Distinguished Professor, Department of Neurology; Director,
UCSF Weill Institute for Neurosciences, University of California, San Francisco,
San Francisco, California
4, 6, 13, 18–24, 50–58, 75, 79, 183–204, 209

J. LARRY JAMESON, MD, PhD
Robert G. Dunlop Professor of Medicine; Dean, Raymond and Ruth Perelman School
of Medicine; Executive Vice President, University of Pennsylvania for the Health
System, Philadelphia, Pennsylvania
3, 4, 7, 8, 25, 26, 31, 32, 120, 171–182, 205, 210

S. ANDREW JOSEPHSON, MD
Professor and Chair, Department of Neurology, University of California,
San Francisco, San Francisco, California
18-21, 23, 51-54, 57, 183–184, 187, 189, 196–202, 209

DENNIS L. KASPER, MD
William Ellery Channing Professor of Medicine;
Professor of Immunology, Department of Immunology, Harvard Medical School,
Boston, Massachusetts
14, 29, 30, 59, 80–106, 108–111, 134, 147, 206

CAROL A. LANGFORD, MD
Harold C. Schott Endowed Chair; Director, Center for Vasculitis Care and Research,
Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland,
Ohio
28, 44, 45, 49, 60, 61, 107, 153–170

LEONARD S. LILLY, MD
Professor of Medicine, Harvard Medical School; Chief, Brigham and Women’s/
Faulkner Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts
11, 12, 15, 33, 34, 36, 112–119, 121–129, 207

DAN L. LONGO, MD
Professor of Medicine, Harvard Medical School; Senior Physician, Brigham
and Women’s Hospital; Deputy Editor, New England Journal of Medicine, Boston,
Massachusetts
9, 10, 27, 39–43, 46, 47, 62–74, 76–78, 150–152, 208

JOSEPH LOSCALZO, MD, PhD
Hersey Professor of the Theory and Practice of Medicine, Harvard Medical School;
Chairman, Department of Medicine; Physician-in-Chief, Brigham and Women’s
Hospital, Boston, Massachusetts
1, 2, 5, 11, 12, 15–17, 33–38, 48, 112–119, 121–146, 148, 149, 207, 211

DAVID B. MOUNT, MD
Assistant Professor of Medicine, Harvard Medical School; Renal Division, Brigham
and Women’s Hospital, Renal Division, Boston VA Healthcare System, Boston,
Massachusetts
1, 2, 38, 48, 141–146, 148, 149

EDWIN K. SILVERMAN, MD, PhD
Professor of Medicine, Harvard Medical School; Chief, Channing Division of
Network Medicine, Department of Medicine, Brigham and Women’s Hospital,
Boston, Massachusetts
5, 16, 17, 35, 37, 130–133, 135–140

NEERAJ K. SURANA, MD, PhD
Assistant Professor in Pediatrics, Molecular Genetics and Microbiology, and
Immunology, Duke University School of Medicine, Durham, North Carolina
14, 29, 30, 59, 80–106, 108–111, 134, 147, 206

Preface

Harrison’s Principles of Internal Medicine (HPIM), the premier medical textbook for students and clinicians, provides a comprehensive resource for understanding of the biological and clinical aspects of quality patient care. Harrison’s Manual of Medicine aims to fulfill a different need: As a concise, fact-rich resource for point-of-care, the Manual presents clinical information drawn from the 20th edition of HPIM, covering the key features of the diagnosis, clinical manifestations, and treatment of the major diseases that are likely to be encountered on a medical inpatient service and in the clinic.

First published 30 years ago, the Manual is well established as a trusted resource for rapid access to clinically practical information. With each edition, it is updated by experts and has become ever more useful with the rapid expansion of medical knowledge and the increasing time constraints associated with heavy patient-care responsibilities in modern health care settings. The Manual’s popularity and value reflect its abbreviated format, which has proven extremely useful for initial diagnosis and management in time-restricted clinical settings. In particular, the book’s full-color format allows readers to locate and use information quickly.

In addition, numerous tables and graphics facilitate decisions at the point of care. Although not a substitute for in-depth analysis of clinical problems, the Manual serves as a ready source of informative summaries that will be useful “on the spot” and that will prepare the reader for more in-depth analysis through more extensive reading at a later time. Of note, McGraw-Hill’s Access Medicine website (www.accessmedicine.com) provides online access to both the Manual and Harrison’s Principles of Internal Medicine, making it very easy to seek additional information when needed. The Manual is also available in a variety of eBook and app formats.

Like previous editions, this latest edition of the Manual is intended to keep up with the continual evolution of internal medicine practices. To this end, every chapter from the prior edition has been closely reviewed and updated, with substantial revisions and new chapters provided where appropriate. The Editors learned much in the process of updating the Manual and we hope that you will find this edition uniquely valuable as a clinical and educational resource.

Acknowledgments

The Editors and McGraw-Hill wish to thank their editorial staff, whose assistance and patience made this edition come out in a timely manner:

From the Editors’ offices: Patricia Duffey; Gregory K. Folkers; Andrew Josephson, MD; H. Clifford Lane, MD; Carol A. Langford, MD; Julie B. McCoy; Anita Ortiz; Elizabeth Robbins, MD; Marie E. Scurti; and Stephanie Tribuna.

From McGraw-Hill: James F. Shanahan, Kim J. Davis, and Catherine H. Saggese.

The Editors also wish to acknowledge contributors to past editions of this Manual, whose work formed the basis for many of the chapters herein: Tamar F. Barlam, MD; Gerhard P. Baumann, MD; Eugene Braunwald, MD; Punit Chadha, MD; Joseph B. Martin, MD, PhD; Michael Sneller, MD; Kenneth Tyler, MD; Sophia Vinogradov, MD; and Jean Wilson, MD.

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