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CONN’S
CURRENT
THERAPY
2021
RICK D. KELLERMAN, MD
Professor and Chair
Department of Family and Community Medicine
University of Kansas School of Medicine–Wichita
Wichita, Kansas

DAVID P. RAKEL, MD
Professor and Chair
Department of Family and Community Medicine
University of New Mexico School of Medicine
Albuquerque, New Mexico
Elsevier
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CONN’S CURRENT THERAPY 2021 ISBN: 978-­0-­323-­79006-­2

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 Contributors

Kashif Abad, MD Arash Arshi, MD

Department of Internal Medicine, University of New Mexico Interventional Cardiology, Cardiovascular Disease, OhioHealth,
School of Medicine, Albuquerque, New Mexico Columbus, Ohio
Chronic Kidney Disease Valvular Heart Disease

Mustafa Abdul-­Hussein, MD, MSCR Danny Avalos, MD

Department of Gastroenterology and Hepatology, St. Anthony Assistant Professor, Gastroenterology, Herbert Wertheim College
Hospital, Oklahoma City, Oklahoma of Medicine–Florida International University, Miami, Florida
Gastroesophageal Reflux Disease (GERD) Inflammatory Bowel Disease

Rodney D. Adam, MD Cecilio M. Azar, MD

Professor of Pathology and Medicine, Aga Khan University, Associate in Medicine, Division of Gastroenterology, Department
Nairobi, Kenya; Professor Emeritus, University of Arizona of Internal Medicine, American University of Beirut Medical
Health Sciences Center, Tucson, Arizona Center, Beirut, Lebanon
Giardiasis Bleeding Esophageal Varices

Paul C. Adams, MD Amir Azarbal, MD

Professor of Medicine, University of Western Ontario; Cardiology Fellow, Fletcher Allen Health Care, Burlington,
Gastroenterologist, University Hospital, London, Ontario, Vermont
Canada Pericarditis
Hemochromatosis
Zachary J. Baeseman, MD, MPH
Nelson Iván Agudelo Higuita, MD Associate Medical Director, ThedaCare Physicians, Wild Rose
Associate Professor, Department of Internal Medicine, University of and Appleton, Wisconsin; Adjunct Professor of Family
Oklahoma Health Sciences Center, Oklahoma City, Oklahoma Medicine, Department of Family Medicine, Medical College of
Plague Wisconsin, Milwaukee, Wisconsin; Adjunct Faculty of Family
Medicine, University of Wisconsin School of Medicine and
Lee Akst, MD Public Health, Madison, Wisconsin
Director, Johns Hopkins Voice Center, Assistant Professor of Vaginal Bleeding in Pregnancy
Otolaryngology–Head and Neck Surgery, The Johns Hopkins
Medical Institute, Baltimore, Maryland
Hoarseness and Laryngitis
Justin Bailey, MD
Associate Professor of Family Medicine, University of Washington
School of Medicine; Director, Procedures Institute, Family
Kelley P. Anderson, MD Medicine Residency of Idaho, Boise, Idaho
Adjunct Clinical Professor of Medicine, University of Wisconsin Gaseousness, Indigestion, Nausea, and Vomiting;
School of Medicine and Public Health, Madison, Wisconsin; Palpitations
Department of Cardiology, Marshfield Clinic, Marshfield,
Wisconsin
Heart Block Mandeep Bajaj, MD
Professor of Medicine, Baylor College of Medicine, Houston,
Texas
Paul Andre, MD Hyperlipidemia
Department of Internal Medicine, School of Medicine, University
of New Mexico, Albuquerque, New Mexico
Tachycardias Vladimer Bakhutashvili, MD
West Virginia University School of Medicine, Morgantown, West
Gregory M. Anstead, MD, PhD Virginia
Staff Physician, Audie L. Murphy Memorial Veterans Affairs Nonalcoholic Fatty Liver Disease
Hospital; Professor, Department of Medicine, University of
Texas Health, San Antonio, Texas Federico Balagué, MD
Coccidioidomycosis Médecin agree, Rheumatology, HFR Fribourg-­hôpital cantonal,
Fribourg, Switzerland
Ann M. Aring, MD Spine Pain
Clinical Assistant Professor of Family Medicine, College of
Medicine and Public Health, The Ohio State University; Bradley E. Barth, MD
Associate Program Director, Family Medicine Residency, Associate Professor, Department of Emergency Medicine,
OhioHealth Riverside Methodist Hospital, Columbus, Ohio University of Kansas School of Medicine, Kansas City, Kansas
Drug Hypersensitivity Reactions; Rhinosinusitis Burns
 Gina M. Basello, DO
Vice Chair, Department of Family Medicine, Director, Family
Medicine Residency Program, Associate Director, Palliative
Medicine, Jamaica Hospital Medical Center; Assistant Clinical
Professor, Family and Social Medicine, Albert Einstein College
of Medicine, New York, New York
Fever
Clara Bloomfield, MD†
Distinguished University Professor, William G. Pace III Professor
of Cancer Research, Cancer Scholar and Senior Advisor, The
Ohio State University Comprehensive Cancer Center, Arthur
G. James Cancer Hospital and Richard J. Solove Research
Institute, The Ohio State University, Columbus, Ohio
Acute Leukemia in Adults

Renee M. Bassaly, DO William Blum, MD

Division Director and Fellowship Director, Associate Professor, Professor and Director, Acute Leukemia Program, Winship
Female Pelvic Medicine and Reconstructive Surgery, Cancer Institute of Emory University, Atlanta, Georgia
Department of Obstetrics and Gynecology, University of South Acute Leukemia in Adults
Florida, Tampa, Florida
Urinary Incontinence Diana Bolotin, MD, PhD
Associate Professor, Director of Dermatologic Surgery, Section of
Adel Bassily-Marcus, MD Dermatology, University of Chicago, Chicago, Illinois
Associate Professor, Surgical Critical Care, The Mount Sinai Nonmelanoma Cancer of the Skin
Hospital, New York, New York
Targeted Temperature Management (Therapeutic Rachel A. Bonnema, MD, MS
Hypothermia) Associate Professor of Medicine, University of Nebraska Medical
Center, Omaha, Nebraska
Julie M. Baughn, MD Contraception
Consultant, Sleep Medicine, Mayo Clinic, Rochester, Minnesota
Pediatric Sleep Disorders David Borenstein, MD
Clinical Professor of Medicine, The George Washington
Sheryl Beard, MD University Medical Center, Washington, DC
Clinical Assistant Professor, Department of Family and Community Spine Pain
Medicine, University of Kansas School of Medicine–Wichita,
Wichita, Kansas Christopher Bossart, MD
Rhinitis Assistant Professor, Department of Emergency Medicine,
University of New Mexico, Albuquerque, New Mexico
Aleksandr Belakovskiy, MD Osteoarthritis
Assistant Professor, Family Medicine, University of Michigan,
Ann Arbor, Michigan Dee Ann Bragg, MD
Contributors

Erectile Dysfunction Clinical Assistant Professor, Department of Family and

Community Medicine, The University of Kansas School of
Ronen Ben-­Ami, MD Medicine–Wichita; Faculty, Via Christi Family Medicine
Head, Infectious Disease Unit, Tel Aviv Sourasky Medical Center, Residency Program, Wichita, Kansas
Tel Aviv, Israel Rubella and Congenital Rubella
Cat Scratch Disease
vi
Scott Bragg, PharmD
Hassan Bencheqroun, MD Associate Professor, Clinical Pharmacy and Outcomes Science,
Assistant Clinical Professor, Pulmonary and Critical Care, Medical University of South Carolina College of Pharmacy;
University of California Riverside School of Medicine, Department of Family Medicine, Medical University of South
Riverside, California Carolina, Charleston, South Carolina
Pruritus Osteoporosis

David I. Bernstein, MD Prasheda Bremjit, MD

Professor Emeritus of Medicine, Division of Immunology, Department of Cardiology, University of New Mexico, Albuquerque,
Allergy, and Rheumatology, Department of Internal New Mexico
Medicine, University of Cincinnati College of Medicine, Congestive Heart Failure
Cincinnati, Ohio
Hypersensitivity Pneumonitis Sylvia L. Brice, MD
Clinical Professor of Dermatology, University of Colorado, Denver,
Jonathan A. Bernstein, MD Colorado
Department of Internal Medicine, Division of Immunology, Viral Diseases of the Skin
Rheumatology and Allergy, University of Cincinnati College of
Medicine, Cincinnati, Ohio John Brill, MD, MPH
Anaphylaxis Vice-­
President, Population Health, Advocate Aurora Health,
Milwaukee, Wisconsin
Kristin Schmid Biggerstaff, MD, MS Gonorrhea
Associate Professor, Opthalmology, Baylor College of Medicine;
Glaucoma Staff, Eye Care Line, Michael E. DeBakey Veteran’s Patricia D. Brown, MD
Affairs Medical Center, Houston, Texas Professor of Medicine, Department of Internal Medicine,
Glaucoma Division of Infectious Diseases, Wayne State University School
of Medicine; Associate Chief of Staff for Medicine, John D.
Mitchell Birt, MD Dingell VA Medical Center, Detroit, Michigan
Assistant Professor, Department of Orthopaedic Surgery, Pyelonephritis
University of Kansas Medical Center, Kansas City, Kansas
Osteomyelitis †Deceased.
Patrick Brown, MD
Associate Professor of Oncology and Pediatrics, The Johns
Hopkins University School of Medicine; Director, Pediatric
Leukemia Program, Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins Medicine, Baltimore, Maryland
Acute Leukemia in Children
Rachel Brown, MBBS
Professor and Chair, Psychiatry and Behavioral Sciences, University
of Kansas School of Medicine–Wichita, Wichita, Kansas
Autism
William E. Cayley Jr., MD, MDiv
Adjunct Clinical Professor, University of Wisconsin School
of Medicine and Public Health; Prevea Family Medicine
Residency, Augusta and Eau Claire, Wisconsin
Chest Pain
Sonia Cerquozzi, MD
Clinical Assistant Professor, Division of Hematology and
Hematologic Malignancies, University of Calgary, Calgary,
Alberta, Canada
Polycythemia Vera

Peter F. Buckley, MD Alvaro Cervera, MD, PhD

Dean, School of Medicine, Virginia Commonwealth University; Consultant Neurologist, Royal Darwin Hospital, Northern
Executive Vice President for Medical Affairs, VCU Health, Territory, Australia
Richmond, Virginia Ischemic Cerebrovascular Disease
Schizophrenia
Rachel Chamberlain, MD
Sarah Burns, DO, MS Associate Program Director, Primary Care Sports Medicine
Assistant Professor, Division of Hospital Medicine, Department Fellowship, Assistant Professor, Department of Family
of Internal Medicine, University of New Mexico School of and Community Medicine, University of New Mexico,
Medicine, Albuquerque, New Mexico Albuquerque, New Mexico
Acute Kidney Injury Osteoarthritis

Kenneth Byrd, DO Lawrence Chan, MD

Assistant Professor, Division of Hematologic Malignancies and Professor, Departments of Medicine, Molecular and Cellular
Cellular Therapeutics, Department of Internal Medicine, Biology, Biochemistry and Molecular Biology, and Molecular and
University of Kansas Medical Center, Kansas City, Kansas Human Genetics, Baylor College of Medicine, Houston, Texas
Disseminated Intravascular Coagulation Hyperaldosteronism; Hyperlipidemia; Hyperprolactinemia

Diego Cadavid, MD Miriam Chan, PharmD

Senior Vice President of Clinical Development, Fulcrum Director of Pharmacy Education, Family Medicine Residency
Therapeutics; Affiliate Instructor in Neurology, University of Program, Riverside Methodist Hospital, Columbus, Ohio
Massachusetts Medical School, Worchester, Massachusetts Drug Hypersensitivity Reactions; Popular Herbs and Nutri-

Contributors
Relapsing Fever tional Supplements

Thomas R. Caraccio, PharmD Zenas Chang, MD, MS

Clinical Pharmacist and Toxicologist, Pharmacy Department, Assistant Professor, Gynecologic Oncology, Indiana University
New York University Winthrop Hospital, Mineola, New York School of Medicine, Indianapolis, Indiana
Medical Toxicology Ovarian Cancer
vii
Peter J. Carek, MD, MS Jimmy Chen, MD
Professor and Chair, Community Health and Family Medicine, Assistant Professor of Pediatrics, Department of Pediatrics, Division
University of Florida, Gainesville, Florida of Hospital Pediatrics, University of Florida–Jacksonville,
Osteoporosis Jacksonville, Florida
Parenteral Fluid Therapy for Infants and Children
Andres F. Carrion, MD
Assistant Professor of Medicine, University of Miami, Miami, Lin Yee Chen, MBBS, MS
Florida Professor, Cardiovascular Division, Department of Medicine,
Cirrhosis University of Minnesota Medical School, Minneapolis,
Minnesota
Amanda S. Cass, PharmD Atrial Fibrillation
Clinical Pharmacist Specialist, Thoracic Oncology, Department
of Pharmaceutical Services, Vanderbilt Ingram Cancer Center, Shingo Chihara, MD
Vanderbilt University Medical Center, Nashville, Tennessee Section of Infectious Diseases, Virginia Mason Medical Center,
Lung Cancer Seattle, Washington
Anthrax
Donald O. Castell, MD
Professor of Medicine, Division of Gastroenterology and Meera Chitlur, MD
Hepatology, Medical University of South Carolina, Charleston, Professor of Pediatrics, Central Michigan University; Pediatric
South Carolina Hematology/Oncology, Children’s Hospital of Michigan;
Gastroesophageal Reflux Disease (GERD) Barnhart-Lusher Hemostasis Research Endowed Chair,
Department of Pediatrics, Wayne State University, Detroit,
Anthony Peter Catinella, MD, MPH Michigan
Associate Professor of Family Medicine, Texas Tech University Hemophilia and Related Conditions
Health Science Center; Chair, Department of Family Medicine–
Transmountain, Paul L. Foster School of Medicine, El Paso,
Texas
Pulmonary Hypertension
 Saima Chohan, MD
Clinical Assistant Professor, Division of Clinical Education,
Arizona College of Osteopathic Medicine, Glendale, Arizona;
Clinical Assistant Professor, Department of Internal Medicine,
Division of Rheumatology, University of Arizona College of
Medicine, Phoenix, Arizona
Gout and Hyperuricemia
Jacob Christensen, DO
Family Medicine, University of Mexico, Albuquerque, New Mexico
Osteoarthritis
Kuang-­Yuh Chyu, MD, PhD
Associate Director, Coronary Intensive Care Unit, Department
of Cardiology, Cedars Sinai Medical Center; Health Sciences
Clinical Professor of Medicine, University of California, Los
Angeles, California
Acute Myocardial Infarction
Joaquin E. Cigarroa, MD
Professor of Medicine, Clinical Chief, Knight Cardiovascular
Institute; Division Head, Cardiology, Oregon Health & Science
University, Portland, Oregon
Congenital Heart Disease
Paul Cleland, MD
Clinical Assistant Professor, Department of Family and
Community Medicine, University of Kansas School of
Medicine–Wichita; Associate Director, University of Kansas
School of Medicine–Wichita Sports Medicine Fellowship,
Wichita, Kansas
Heat-­Related Illness
Carlo Contini, MD
Full Professor of Infectious Diseases, Director of Infectious
Diseases Unit, Department of Medical Sciences, University of
Ferrara, Ferrara, Italy
Toxoplasmosis
Ashley Cooper, MD
Assistant Professor of Medicine, Tulane School of Medicine, New
Orleans, Louisiana
Juvenile Idiopathic Arthritis
Allison K. Cormier, MD
Assistant Professor of Medicine, Tulane School of Medicine, New
Orleans, Louisiana
Human Immunodeficiency Virus: Treatment and Prevention
Michael L. Corriveau, MD
Assistant Clinical Professor of Internal Medicine, The Ohio State
University School of Medicine; Pulmonologist, Chalmers P.
Wylie VA Ambulatory Care Center, Columbus, Ohio
Chronic Obstructive Pulmonary Disease
Bart L. Cox, MD
Associate Professor of Medicine, Department of Cardiology,
University of New Mexico, Albuquerque, New Mexico
Congestive Heart Failure
Burke A. Cunha, MD
Professor, State University of New York School of Medicine,
Stony Brook, New York; Chief, Infectious Disease Division,
Winthrop–University Hospital, Mineola, New York
Babesiosis; Viral and Mycoplasmal Pneumonias

Matthew K. Cline, MD Cheston B. Cunha, MD

Contributors

MUSC Affiliate Professor (Anderson/Family Medicine), Medical Medical Director, Antimicrobial Stewardship, Infectious Disease
University of South Carolina, Charleston, South Carolina Division, Alpert School of Medicine, Brown University,
Antepartum Care Providence, Rhode Island
Babesiosis; Viral and Mycoplasmal Pneumonias
Laura C. Coates, MBChB, PhD
Associate Professor, Nuffield Department of Orthopaedics, Amy E. Curry, MD
Rheumatology and Musculoskeletal Sciences, University of Clinical Associate Professor, Department of Family and
viii Oxford, Oxford, Great Britain Community Medicine, University of Kansas School of
Psoriatic Arthritis Medicine–Wichita; Via Christi Family Medicine Residency,
Wichita, Kansas
August Colenbrander, MD Pelvic Inflammatory Disease
Affiliate Senior Scientist, Rehabilitation Engineering Research
Center, Smith-­Kettlewell Eye Research Institute, San Francisco, Julia Dai, MD
California Associate Professor, Director of Dermatologic Surgery, Section of
Vision Rehabilitation Dermatology, University of Chicago, Chicago, Illinois
Nonmelanoma Cancer of the Skin
Tracie C. Collins, MD, MPH, MHCDS
Dean and Professor, College of Population Health, University of Cori L. Daines, MD
New Mexico, Albuquerque, New Mexico Professor, Division Chief, Director, Pediatric Pulmonary and Sleep
Peripheral Artery Disease Medicine Center, Tucson Cystic Fibrosis Center; Director,
Pediatric Pulmonary Center, The University of Arizona College
Ryan M. Commins, MD of Medicine, Tucson, Arizona
Internal Medicine, Georgetown University Medical Center, Cystic Fibrosis
Washington, DC
High Altitude Illness Oriana M. Damas, MD
Assistant Professor, Director of Translational Studies for the
Christine Conageski, MD Crohn’s and Colitis Center, Division of Gastroenterology,
Associate Professor, Obstetrics and Gynecology, University of Department of Medicine, University of Miami Miller School of
Colorado, Aurora, Colorado Medicine, Miami, Florida
Vulvar Neoplasia Inflammatory Bowel Disease

John M. Conly, MD Beth A. Damitz, MD

Professor of Medicine and Microbiology, Immunology & Infectious Associate Professor, Family and Community Medicine, Medical
Diseases, University of Calgary, Calgary, Alberta, Canada College of Wisconsin, Milwaukee, Wisconsin
Methicillin-­Resistant Staphylococcus aureus Immunization Practices
Natalie C. Dattilo, PhD
Director of Psychology, Department of Psychiatry, Brigham and
Women’s Hospital, Boston, Massachusetts
Generalized Anxiety Disorder; Posttraumatic Stress Disorder
Raul Davaro, MD
Associate Professor of Clinical Medicine, University
Massachusetts, Worcester, Massachusetts
Smallpox; Whooping Cough
Kevin A. David, MD
Associate Professor of Medicine, Rutgers Robert Wood Johnson
Medical School; Member, Rutgers Cancer Institute of New
Jersey, New Brunswick, New Jersey
Non-­Hodgkin Lymphoma
André de Leon, MD
Family Medicine/Sports Medicine, OhioHealth Primary Care and
Pediatric Physicians, Delaware, Ohio
Chronic Diarrhea
Tate de Leon, MD
Faculty, Family Medicine, Eisenhower Family Medicine
Residency, Rancho Mirage, California
Acute Diarrhea
John N. Dorsch, MD
Professor Emeritus, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita,
Wichita, Kansas
Red Eye
of Chad Douglas, MD, PharmD
Assistant Professor of Family and Preventive Medicine, Medical
& Didactic Education Director, University of Oklahoma
Health Sciences Center; Department of Family and Preventive
Medicine, Medical Director–OU Physicians Health and
Wellness Clinic, Oklahoma City, Oklahoma
Erythema Multiforme
Shannon Dowler, MD
Adjunct Associate Professor, Department of Family Medicine,
University of North Carolina Chapel Hill, Asheville, North
Carolina
Nongonococcal Urethritis
Douglas A. Drevets, MD
Professor and Chief, Section of Infectious Diseases, University of
Oklahoma Health Sciences Center; Staff Physician, Veterans
Affairs Medical Center, Oklahoma City, Oklahoma
Plague

Alexei O. DeCastro, MD Samuel C. Dudley Jr., MD, PhD

Associate Professor, Department of Family Medicine, Medical Professor, Department of Medicine, Division of Cardiology,
University of South Carolina, Charleston, South Carolina University of Minnesota, Minneapolis, Minnesota
Osteoporosis Atrial Fibrillation

Katharine C. DeGeorge, MD, MS Peter R. Duggan, MD

Associate Professor, Department of Family Medicine, University Associate Clinical Professor of Medicine, University of Calgary,
of Virginia, Charlottesville, Virginia Calgary, Alberta, Canada

Contributors
Bacterial Pneumonia; Asthma in Children Polycythemia Vera

Thomas G. DeLoughery, MD Kim Eagle, MD

Professor of Medicine, Pathology, and Pediatrics, Oregon Health & Albion Walter Hewlett Professor of Internal Medicine, Director,
Science University, Portland, Oregon Cardiovascular Center, University of Michigan Health System,
Hemolytic Anemias Ann Arbor, Michigan
Angina Pectoris
ix
Atul Deodhar, MD
Professor of Medicine, Division of Arthritis & Rheumatic Diseases, Leigh M. Eck, MD
Oregon Health & Science University, Portland, Oregon Associate Professor of Medicine, Program Director–Internal
Axial Spondyloarthritis Medicine Residency Program, Vice Chair of GME–Department
of Internal Medicine, The University of Kansas Health System,
Urmi Desai, MD, MS Kansas City, Kansas
Director, Foundations of Clinical Medicine Clerkships, Assistant Thyroiditis
Professor of Medicine, Center for Family and Community
Medicine, Columbia University Irving Medical Center, New Genevieve L. Egnatios, MD
York, New York Affiliated Dermatology, Scottsdale, Arizona
Vulvovaginitis Contact Dermatitis

Clio Dessinioti, MD, MSc, PhD Wissam El Atrouni, MD, MSc

Dermatologist, Andreas Sygros Hospital, Athens, Greece Associate Professor, Division of Infectious Diseases, University of
Parasitic Diseases of the Skin Kansas Hospital, Kansas City, Kansas
Osteomyelitis
Michael P. Diamond, MD
Leon Henri Charbonnier Endowed Chair in Reproductive Dirk M. Elston, MD
Endocrinology, Professor of Obstetrics and Gynecology, Associate Professor and Chairman, Department of Dermatology and
Dean for Research, Medical College of Georgia; Senior Vice Dermatologic Surgery, Medical University of South Carolina,
President for Research, Augusta University, Augusta, Georgia Charleston, South Carolina
Infertility Diseases of the Hair

Geoffrey A. Donnan, MD
Department of Neurology, University of Melbourne Faculty of
Medicine, Dentistry, and Health Sciences; Florey Neuroscience
Institutes, Carlton South, Victoria, Australia
Ischemic Cerebrovascular Disease
 John M. Embil, MD
Professor, Departments of Internal Medicine (Section of
Infectious Diseases) and Medical Microbiology, Consultant,
Infectious Diseases, Director, BSc(Med) Program, University of
Manitoba; Medical Director, Infection Prevention and Control
Unit, Health Sciences Centre and Winnipeg Regional Health
Authority, Winnipeg, Manitoba, Canada
Blastomycosis
Scott K. Epstein, MD
Dean for Educational Affairs and Professor of Medicine, Tufts
University School of Medicine, Boston, Massachusetts
Acute Respiratory Failure
William E. Fisher, MD
Professor, Clinical Vice-­Chair and Chief, Division of General
Surgery, George L. Jordan, MD Chair of General Surgery,
Vice Chair, Clinical Affairs, Director, Elkins Pancreas Center,
Michael E. DeBakey Department of Surgery, Chief, Surgery
Service Line, Baylor St. Luke’s Medical Center, Houston, Texas
Acute and Chronic Pancreatitis
Maria Fleseriu, MD
Professor of Medicine and Neurological Surgery, Director of
Pituitary Center, Oregon Health & Science University, Portland,
Oregon
Adrenocortical Insufficiency; Hypopituitarism

Susan Evans, MD Donald C. Fletcher, MD

Assistant Professor, Department of Family Medicine, University Adjunct Associate Professor, Department of Ophthalmology,
of Nebraska Medical Center University of Kansas School of Medicine, Kansas City, Kansas
Iron Deficiency Anemia Vision Rehabilitation

Andrew M. Evens, DO, MSc Sarah Forsberg, PsyD

Professor of Medicine, Rutgers Robert Wood Johnson Medical
School; Associate Director for Clinical Services, Rutgers Cancer
Institute of New Jersey; Director, Lymphoma Program, Division
of Blood Disorders, Medical Director, Oncology Service Line,
RWJBarnabas Health, New Brunswick, New Jersey
Non-­Hodgkin Lymphoma
J. Barry Fagan, MD
Service Chief, Specialty Medicine, Central Ohio VA Healthcare
System, Columbus, Ohio
Chronic Obstructive Pulmonary Disease
Associate Clinical Professor, Department of Psychiatry, Eating
Disorders Program, University of California, San Francisco,
San Francisco, California
Eating Disorders
Jeffrey Michael Foster, DO
Anesthesiology and Interventional Pain Medicine, Saint Luke’s
Hospital of Kansas City; Clinical Assistant Professor of
Anesthesiology, University of Missouri at Kansas City, Kansas
City, Missouri
Fibromyalgia

Anna Faris, MD Jennifer Frank, MD

Resident Physician, Department of Urology, University of Chief Medical Officer, Clinically Integrated Network, Theda
Contributors

Michigan, Ann Arbor, Michigan Care Physicians, Neenah, Wisconsin

Trauma to the Genitourinary Tract Syphilis

Anthony J. Faugno III, MD Ellen W. Freeman, PhD

Instructor in Medicine, Department of Medicine, Division of Research Professor, Obstetrics/Gynecology, Perelman School of
Pulmonary, Critical Care and Sleep, Tufts Medical Center, Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Boston, Massachusetts Premenstrual Syndrome
x Acute Respiratory Failure
Ruchi Gaba, MD
Kinder Fayssoux, MD Endocrinology, Diabetes and Metabolism, Baylor College of
Center for Family Medicine, Eisenhower Medical Associates, La Medicine, Houston, Texas
Quinta, California Hyperaldosteronism
Bacterial Infections of the Urinary Tract in Women
Melissa Gaines, MD
Dorianne Feldman, MD, MSPT Cox Senior Health, Geriatrics Division, Springfield, Missouri
Medical Director, Inpatient Rehabilitation, Department of Constipation
Physical Medicine and Rehabilitation, Johns Hopkins
University School of Medicine, Baltimore, Maryland Marc G. Ghany, MD, MHSc
Rehabilitation of the Stroke Patient Clinical Research Section, Liver Diseases Branch, National
Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, Maryland
Terry D. Fife, MD Hepatitis A, B, D, and E
Director, Otoneurology and Balance Disorders, Barrow
Neurological Institute, Phoenix, Arizona
Ménière’s Disease Muhammad Ahmad Ghazi, MD
Family Physician, Jacksonville, Florida
Pruritus Ani and Vulvae
David J. Finley, MD
Co-­
Director, Complex Airway Program, Surgeon, Thoracic
Service, Memorial Sloan Kettering Cancer Center, New York,
Geoffrey Gibney, MD
Co-­
Leader Melanoma Program, Lombardi Comprehensive
New York
Cancer Center, Medstar Georgetown University Hospital,
Pleural Effusions and Empyema
Washington, DC
Melanoma
Jonathon Firnhaber, MD, MAEd, MBA
Residency Program Director, Department of Family Medicine,
East Carolina University, Greenville, North Carolina
Donald L. Gilbert, MD, MS
Professor of Pediatrics and Neurology, Cincinnati Children’s
Diseases of the Nail
Hospital Medical Center, Cincinnati, Ohio
Gilles de la Tourette Syndrome
Karissa Gilchrist, MD
Instructor, Department of Family and Community Medicine,
University of Kansas School of Medicine–Wichita, Wichita,
Kansas
Bacterial Diseases of the Skin
Erin A. Gillaspie, MD, MPH
Assistant Professor of Thoracic Surgery, Head of Thoracic Surgery
Robotics, Vanderbilt University Medical Center, Nashville,
Tennessee
Lung Cancer
Tarvinder Gilotra, MD
Department of Infectious Disease, SUNY Upstate Medical
University, Syracuse, New York
Intestinal Parasites
Mark T. Gladwin, MD
Jack D. Myers Distinguished Professor and Chair, Department
of Medicine, Director, Pittsburgh Heart, Lung, Blood and
Vascular Medicine Institute, UPMC and the University of
Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Sickle Cell Disease
Stephen J. Gluckman, MD
Professor of Medicine, Perelman School of Medicine, University
of Pennsylvania, Philadelphia, Pennsylvania
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Andrew W. Goddard, MD
Professor of Psychiatry, University of California, San Francisco;
Fresno Medical Education & Research Program, San Francisco,
California
Generalized Anxiety Disorder
Kyle Goerl, MD
Team Physician, Kansas State University Athletics; Sports
and Family Medicine, Lafene Health Center, Kansas State
University, Manhattan, Kansas; Clinical Assistant Professor,
Department of Family and Community Medicine, University
of Kansas School of Medicine–Wichita, Wichita, Kansas
Bursitis and Tendinopathy
Mark S. Gold, MD
Professor, Department of Psychiatry, Washington University
School of Medicine, St. Louis, Missouri
Drug Use Disorders
Joshua N. Goldstein, MD, PhD
Professor of Emergency Medicine, Harvard Medical School; MGH
Endowed Professor of Emergency Research, Massachusetts
General Hospital, Boston, Massachusetts
Intracerebral Hemorrhage
Marlis González-­Fernández, MD, PhD
Associate Professor, Departments of Physical Medicine and
Rehabilitation and Orthopaedic Surgery, Vice Chair, Clinical
Affairs, Department of Physical Medicine and Rehabilitation,
The Johns Hopkins University School of Medicine, Baltimore,
Maryland
Rehabilitation of the Stroke Patient
Gregory Goodwin, MD
Assistant Professor of Pediatrics, Harvard Medical School; Senior
Associate Physician in Pediatrics, Boston Children’s Hospital,
Boston, Massachusetts
Diabetes Mellitus in Children
Aidar R. Gosmanov, MD, PhD, DMSc
Chief, Endocrinology Section, Stratton Veterans Affairs
Medical Center; Associate Professor of Medicine, Division of
Endocrinology, Albany Medical College, Albany, New York
Diabetic Ketoacidosis
Luigi Gradoni, PhD
Research Director, Unit of Vector-­Borne Diseases, Department
of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
Leishmaniasis
Timothy P. Graham, MD
Program Director, Mount Carmel Family Medicine Residency;
Chair, Department of Family Medicine, Mount Carmel St.
Ann’s Hospital, Westerville, Ohio
Hypertension
Jane M. Grant-­Kels, MD
Professor of Dermatology, Pathology and Pediatrics, Founding
Chair Emeritus and Vice Chair, Department of Dermatology,
Director, the Cutaneous Oncology Center and Melanoma
Program, University of Connecticut Health Center, Farmington,
Connecticut
Nevi
Kristine Grdinovac, MD
The University of Kansas Healthcare System, Section of
Endocrinology, Kansas City, Kansas
Diabetes Mellitus in Adults
Leslie A. Greenberg, MD
Associate Professor of Family and Community Medicine,
University of Nevada Reno School of Medicine; Assistant
Program Director, University of Nevada Reno Family Medicine
Contributors
Residency Program, Reno, Nevada
Keloids
William M. Greene, MD
Associate Professor, Addiction Medicine Division, Department
of Psychiatry, University of Florida College of Medicine,
Gainesville, Florida
Drug Use Disorders xi
Joseph Greensher, MD
Medical Director and Associate Chair, Department of Pediatrics,
Long Island Regional Poison and Drug Information Center,
Winthrop-­University Hospital, Mineola, New York; Professor
of Pediatrics, Stony Brook University Medical Center School of
Medicine, Stony Brook, New York
Medical Toxicology
David S. Gregory, MD
Faculty Physician, Virginia Tech–Carilion Clinic Family Medicine
Residency, Roanoke, Virginia; Assistant Clinical Professor of
Family Medicine, Virginia Commonwealth University School
of Medicine, Richmond, Virginia; Associate Clinical Professor
of Family Medicine, University of Virginia School of Medicine,
Charlottesville, Virginia
Resuscitation of the Newborn
Justin Greiwe, MD
Clinical Assistant Professor of Medicine, Division of Immunology,
Allergy, and Rheumatology, University of Cincinnati,
Cincinnati, Ohio
Anaphylaxis
Tawanda Gumbo, MD
Associate Professor of Medicine, University of Texas Southwestern
Medical School; Attending Physician, Parkland Memorial
Hospital and University Hospital–St. Paul, Dallas, Texas
Tuberculosis and Other Mycobacterial Diseases
 Melissa Hague, MD
Clinical Associate Professor, Obstetrics and Gynecology,
University of Kansas School of Medicine–Wichita, Wichita,
Kansas
Female Sexual Dysfunction
Rebat M. Halder, MD
Professor Emeritus and Chair Emeritus, Department of
Dermatology, Howard University College of Medicine,
Washington, DC
Pigmentary Disorders
Alan M. Hall, MD
Associate Professor of Internal Medicine and Pediatrics, Divisions
of Hospital Medicine and Hospital Pediatrics, Departments
of Internal Medicine and Pediatrics, University of Kentucky
College of Medicine, Lexington, Kentucky
Parenteral Fluid Therapy for Infants and Children
Ronald Hall II, PharmD, MSCS
Associate Professor, Pharmacy Practice, Texas Tech University
Health Sciences Center, Dallas, Texas
Tuberculosis and Other Mycobacterial Diseases
Lynn E. Harman, MD
Department of Surgery and Ophthalmology, James A. Haley
Veterans’ Hospital, Tampa, Florida
Dry Eye Syndrome; Uveitis
Kari R. Harris, MD
Associate Professor, Department of Pediatrics, University of
Kansas School of Medicine–Wichita, Wichita, Kansas
Adolescent Health
Contributors
Taylor B. Harrison, MD
Associate Professor, Neuromuscular Division, Program Director,
Clinical Neurophysiology Fellowship, Department of Neurology,
Emory University, Atlanta, Georgia
Myasthenia Gravis
xii Adam L. Hartman, MD
Program Director, Division of Clinical Research, National
Institute of Neurological Disorders and Stroke, National
Institutes of Health, Bethesda, Maryland
Epilepsy in Infants and Children
James W. Haynes, MD
Professor and Chair, Department of Family Medicine, The
University of Tennessee Health Sciences Center College of
Medicine–Chattanooga; Family Medicine, Erlanger Health
System, Chattanooga, Tennessee
Uterine Leiomyoma
Joel J. Heidelbaugh, MD
Clinical Professor, Departments of Family Medicine and Urology,
Medical Education and Clerkship Director, Department of
Family Medicine, Director, Patients and Populations Branch,
University of Michigan Medical School, Ann Arbor, Michigan
Erectile Dysfunction
Stacey A. Hinderliter, MD
Associate Director, Riverside Brentwood Family Medicine
Residency, Newport News, Virginia; Assistant Professor,
Pediatrics, Edward Via College of Osteopathic Medicine,
Blacksburg, Virginia; Clinical Assistant Professor, Family
Medicine, Virginia Commonwealth University–Medical
College of Virginia, Richmond, Virginia
Resuscitation of the Newborn
Molly A. Hinshaw, MD
Associate Professor of Dermatology, Section Chief of
Dermatopathology, Director of Dermatology Nail Clinic,
University of Wisconsin School of Medicine and Public Health,
Dermatopathology Laboratory, Madison, Wisconsin
Connective Tissue Disorders; Cutaneous Vasculitis
Brandon Hockenberry, MD
Sports Medicine Physician, Renown Sports Medicine, Reno,
Nevada
Sports-­Related Head Injuries
Raymond J. Hohl, MD, PhD
Director, Penn State Cancer Institute, Hershey, Pennsylvania
Thalassemia
Therese Holguin, MD
Assistant Professor of Dermatology, University of New Mexico,
Albuquerque, New Mexico
Fungal Infections of the Skin
Sarah A. Holstein, MD, PhD
Associate Professor, Department of Internal Medicine, University
of Nebraska Medical Center, Omaha, Nebraska
Thalassemia
Michael Holyoak, MD
St. Luke’s Clinic–Idaho Endocrinology, Meridian, Idaho
Thyroid Cancer
Gretchen Homan, MD
Associate Professor, Department of Pediatrics, University of
Kansas School of Medicine–Wichita, Wichita, Kansas
Pediatric Failure to Thrive
Kevin Hommema, BSME
Principal Research Scientist, Battelle, Columbus, Ohio
Biologic Agents Reference Chart; Toxic Chemical Agents
Reference Chart
Laurie A.M. Hommema, MD
Associate Program Director, Family Medicine Residency,
Riverside Methodist Hospital; Medical Director, Provider and
Associate Well-­Being, Quality and Patient Safety, OhioHealth,
Columbus, Ohio
Biologic Agents Reference Chart, Toxic Chemical Agents
Reference Chart
Leora Horn, MD, MSc
Ingram Associate Professor of Cancer Research, Associate
Professor of Medicine, Vanderbilt Ingram Cancer Center,
Vanderbilt University Medical Center, Nashville, Tennessee
Lung Cancer
Ahmad Reza Hossani-­Madani, MD, MS
Dermatologist, Kaiser Permanente, Upper Marlboro, Maryland
Pigmentary Disorders
Steven A. House, MD
Professor, Department of Family and Geriatric Medicine,
Program Director, University of Louisville/Glasgow Family
Medicine Residency, Glasgow, Kentucky
Pain; Palliative and End-­of-­Life Care
Sarah Houssayni, MD
Clinical Associate Professor, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita;
Pediatrics, Via Christi Family Medicine Residency, Wichita,
Kansas
Encopresis
William J. Hueston, MD Casey R. Johnson, MD, MS
Associate Provost for Education, Senior Associate Dean for Medical Resident Physician, Department of Pediatric and Adolescent
Education, Medical College of Wisconsin, Milwaukee, Wisconsin Medicine, Mayo Clinic, Rochester, Minnesota
Hyperthyroidism; Hypothyroidism Obesity in Adults; Obesity in Children

Alison N. Huffstetler, MD Lisa M. Johnson, MD

Assistant Professor of Family Medicine, Virginia Commonwealth Associate Professor, Department of Family Medicine, University
University, Richmond, Virginia of Cincinnati College of Medicine, Cincinnati, Ohio
Bacterial Pneumonia Acne Vulgaris; Rosacea

Scott A. Hundahl, MD Joshua S. Jolissaint, MD

Professor and Chief of Surgery, University of California–Davis Department of Surgery, Brigham and Women’s Hospital, Boston,
School of Medicine, Sacramento, California Massachusetts
Tumors of the Stomach Atelectasis; Pancreatic Cancer

Stephen P. Hunger, MD R. Gregory Juckett, MD, MPH

Professor of Pediatrics, University of Pennsylvania Perelman School Professor Emeritus, West Virginia University School of Medicine,
of Medicine; Chief, Division of Pediatric Oncology, Director, Morgantown, West Virginia
Center for Childhood Cancer Research, Jeffrey E. Perelman Campylobacter
Distinguished Chair, Department of Pediatrics, Children’s
Hospital of Philadelphia, Philadelphia, Pennsylvania Marc A. Judson, MD
Acute Leukemia in Children Chief, Division of Pulmonary and Critical Care Medicine, Albany
Medical College, Albany, New York
Gretchen M. Irwin, MD, MBA Sarcoidosis
Associate Dean for Graduate Medical Education, Associate Professor,
Department of Family and Community Medicine, University of Tamilarasu Kadhiravan, MD
Kansas School of Medicine–Wichita, Wichita, Kansas Additional Professor of Medicine, Jawaharlal Institute of
Otitis Media Postgraduate Medical Education and Research, Puducherry, India
Typhoid Fever
Daniel Isaac, DO
Assistant Professor of Medicine, Division of Hematology/ Rachna Kalia, MD
Oncology, College of Human Medicine, Michigan State Clinical Assistant Professor, Department of Psychiatry and
University, East Lansing, Michigan Behavioral Sciences, University of Kansas School of Medicine–
Chronic Leukemias Wichita, Wichita, Kansas

Contributors
Obsessive-­Compulsive Disorder
Gerald A. Isenberg, MD
Professor of Surgery, Director, Surgical Undergraduate Medical Jessica Rachel Kanter, MD
Education, Sidney Kimmel Medical College; Program Director, Fellow, Reproductive Endocrinology and Infertility, Hospital of
Colorectal Surgery Residency, Thomas Jefferson University the University of Pennsylvania, Philadelphia, Pennsylvania
Hospitals, Philadelphia, Pennsylvania Infertility
Tumors of the Colon and Rectum
xiii
Dilip R. Karnad, MD
Alan C. Jackson, MD Consultant in Critical Care, Jupiter Hospital, Thane, Maharashtra,
Professor, Section of Neurology, Internal Medicine, University of India
Manitoba, Winnipeg, Manitoba, Canada Tetanus
Rabies
Rudruidee Karnchanasorn, MD
Kurt M. Jacobson, MD Associate Professor, Internal Medicine, The University of Kansas
Associate Professor of Medicine, Cardiovascular Medicine Medical Center, Kansas City, Kansas
Division, University of Wisconsin School of Medicine and Thyroid Cancer
Public Health, Madison, Wisconsin
Mitral Valve Prolapse Andreas Katsambas, MD, PhD
Professor of Dermatology, University of Athens School of
Jose A. Jaller, MD Medicine, Athens, Greece
Department of Medicine, Division of Dermatology, Albert Parasitic Diseases of the Skin
Einstein College of Medicine, Bronx, New York
Venous Ulcers Ben Z. Katz, MD
Professor of Pediatrics, Northwestern University Feinberg School
W. Ennis James, MD of Medicine, Chicago, Illinois
Assistant Professor, Pulmonary and Critical Care Medicine, Medical Infectious Mononucleosis
University of South Carolina, Charleston, South Carolina
Sarcoidosis Rebecca Katzman, MD
Clinical Instructor, Family Medicine, University of Washington,
Xiaoming Jia, MD Seattle, Washington
Instructor, Medicine, Baylor College of Medicine, Houston, Texas Palpitations
Hyperlipidemia
 Daniel I. Kaufer, MD†
Chief, Cognitive & Behavioral Neurology, Director, UNC Memory
Disorders Program, Departments of Neurology and Psychiatry,
University of North Carolina, Chapel Hill, North Carolina
Alzheimer’s Disease
Andrew M. Kaunitz, MD
University of Florida Term Professor and Associate Chairman,
Department of Obstetrics and Gynecology, University of
Florida College of Medicine–Jacksonville; Medical Director
and Director of Menopause and Gynecologic Ultrasound
Services, University of Florida Women’s Health Specialists–
Emerson, Jacksonville, Florida
Menopause
B. Mark Keegan, MD
Division Chair, Multiple Sclerosis and Autoimmune Neurology,
Professor of Neurology, Mayo Clinic College of Medicine,
Rochester, Minnesota
Multiple Sclerosis
Rick D. Kellerman, MD
Professor and Chair, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita,
Wichita, Kansas
Chikungunya; Zika Virus Disease
Scott Kellermann, MD, MPH
Faculty, University of San Francisco, San Francisco, California;
Founder, Bwindi Community Hospital, Buhoma, Uganda
Chikungunya; Zika Virus Disease
Christina M. Kelly, MD
Department of Family Medicine, Womack Army Medical Center
Contributors
Family Medicine Residency, Fort Bragg, North Carolina;
Assistant Professor, Family Medicine, Uniformed Services
University of the Health Sciences, Bethesda, Maryland
Ectopic Pregnancy
Sheevaun Khaki, MD
Assistant Professor, General Pediatrics, Medical Director,
xiv Mother Baby Unit, Director of Pediatric Electives, Oregon
Health & Science University, Portland, Oregon
Infant Hyperbilirubinemia
Arthur Y. Kim, MD
Associate Professor of Medicine, Harvard Medical School;
Division of Infectious Diseases, Massachusetts General
Hospital, Boston, Massachusetts
Hepatitis C
Haejin Kim, MD
Senior Staff Allergist, Division of Allergy and Clinical
Immunology, Department of Internal Medicine, Henry Ford
Health System, Detroit, Michigan
Hypersensitivity Pneumonitis
Robert S. Kirsner, MD, PHD
Chair & Harvey Blank Professor, Dr. Phillip Frost Department
of Dermatology & Cutaneous Surgery, University of Miami
Miller School of Medicine, Miami, Florida
Venous Ulcers
Sonam Kiwalkar, MBBS
Clinical Instructor, Division of Arthritis and Rheumatology,
Oregon Health & Science University, Portland, Oregon
Axial Spondyloarthritis
†Deceased.
Amanda Kolb, MD
Instructor, Department of Family Medicine, University of
Virginia, Charlottesville, Virginia
Asthma in Children
Bhanu Prakash Kolla, MD, MRCPsych
Senior Associate Consultant, Center for Sleep Medicine,
Department of Psychiatry and Psychology, Mayo Clinic and
Foundation; Assistant Professor of Psychiatry and Psychology,
Mayo Clinic College of Medicine, Rochester, Minnesota
Sleep Disorders
Frederick K. Korley, MD
Robert E. Meyerhoff Assistant Professor of Emergency Medicine,
The Johns Hopkins University School of Medicine; Staff, The
Johns Hopkins Medical Institutions, Baltimore, Maryland
Disturbances Due to Cold
Adrienne N. Kovalsky, DO, MPH
Assistant Professor of Medicine, Department of Hospital
Medicine, Georgetown University Hospital, Washington,
District of Columbia
High Altitude Illness
Megan Krause, MD
Assistant Professor, Division of Allergy, Clinical Immunology,
and Rheumatology, University of Kansas School of Medicine,
Kansas City, Kansas
Rheumatoid Arthritis
Eric H. Kraut, MD
Professor of Medicine, Director, Benign Hematology, Division of
Hematology, The Ohio State University, Columbus, Ohio
Platelet-­Mediated Bleeding Disorders
Lakshmanan Krishnamurti, MD
Professor of Pediatrics, Division of Hematology/Oncology,
Children’s Hospital of Pittsburgh, University of Pittsburgh
Medical Center, Pittsburgh, Pennsylvania
Sickle Cell Disease
Kumar Krishnan, MD
Assistant Professor of Medicine, Harvard Medical School;
Division of Gastroenterology, Massachusetts General Hospital,
Boston, Massachusetts
Dysphagia and Esophageal Obstruction
Zachary Kuhlmann, DO
Clinical Associate Professor, Residency Program Director,
Department of Obstetrics and Gynecology, University of
Kansas School of Medicine–Wichita, Wichita, Kansas
Endometriosis
Roshni Kulkarni, MD
Professor Emerita, Michigan State University Center for Bleeding
and Clotting Disorders, Department of Pediatrics and Human
Development, College of Human Medicine, Michigan State
University, East Lansing, Michigan
Hemophilia and Related Conditions
Seema Kumar, MD
Professor of Pediatrics, Chair, Division of Pediatric Endocrinology
and Metabolism, Program Director, Pediatric Endocrinology
Fellowship, Department of Pediatrics, Mayo Clinic, Rochester,
Minnesota
Obesity in Adults; Obesity in Children
Mary R. Kwaan, MD, MPH
Health Sciences Associate Clinical Professor of Surgery, David
Geffen School of Medicine at University of California, Los
Angeles, Los Angeles, California
Hemorrhoids, Anal Fissure, and Anorectal Abscess and Fistula
Robert A. Kyle, MD
Professor of Medicine, Laboratory Medicine, and Pathology,
Mayo Clinic College of Medicine, Rochester, Minnesota
Multiple Myeloma
Lucius Marion Lampton, MD
Private Practice, Magnolia Clinic, Magnolia, Mississippi; Clinical
Professor of Family Medicine, William Carey University College
of Osteopathic Medicine, Hattiesburg, Mississippi; Clinical
Associate Professor of Family and Community Medicine,
Tulane University School of Medicine, New Orleans, Louisiana
COVID-19; Yellow Fever
Richard A. Lange, MD, MBA
President, Texas Tech University Health Sciences Center El Paso;
Dean, Paul L. Foster School of Medicine, El Paso, Texas
Congenital Heart Disease
Fabienne Langlois, MD
Assistant Professor, Division of Endocrinology, Department
of Medicine, Universite de Sherbrooke, Fleurimont, Quebec,
Canada
Adrenocortical Insufficiency; Hypopituitarism
Jerome Larkin, MD
Assistant Professor of Medicine, Infectious Diseases,
Alpert Medical School, Brown University, Providence, Rhode
Island
Severe Sepsis
Christine L. Lau, MD
George Minor Professor of Surgery, University of Virginia Health
System, Charlottesville, Virginia
Atelectasis
Susan Lawrence-­Hylland, MD
Clinical Assistant Professor, Rheumatology Section, University of
Wisconsin Hospital and Clinics, Madison, Wisconsin
Connective Tissue Disorders; Cutaneous Vasculitis
Lydia U. Lee, MD
Clinical Lecturer, Department of Family Medicine, University of
Michigan, Ann Arbor, Michigan
Postpartum Depression
Jerrold B. Leikin, MD
Director of Medical Toxicology, NorthShore University,
HealthSystem–OMEGA, Glenbrook Hospital, Glenview,
Illinois; Clinical Professor of Medicine, Pritzker School of
Medicine, University of Chicago, Chicago, Illinois
Disturbances Due to Cold
Scott Leikin, DO
Critical Care Medicine Fellow, Icahn School of Medicine at
Mount Sinai, New York, New York
Targeted Temperature Management (Therapeutic
Hypothermia); Disturbances Due to Cold
Alexander K.C. Leung, MBBS
Clinical Professor of Pediatrics, University of Calgary, Calgary,
Alberta, Canada
Nocturnal Enuresis
Martin M. LeWinter, MD
Professor of Medicine and Molecular Physiology and Biophysics,
University of Vermont Larner College of Medicine; Attending
Cardiologist, University of Vermont Medical Center,
Burlington, Vermont
Pericarditis
Jennifer Lewis, MD, MPH
Assistant Professor of Medicine, Vanderbilt Ingram Cancer Center,
Vanderbilt University Medical Center; VA Quality Scholars
Fellow, Geriatric Research Education and Clinical Center, VA
Tennessee Valley Healthcare System, Nashville, Tennessee
Lung Cancer
Ming Li, MD, PhD
Section of Endocrinology, Phoenix VA Health Care System;
Department of Internal Medicine, University of Arizona,
College of Medicine at Phoenix, Phoenix, Arizona
Hyperprolactinemia
Tyler K. Liebenstein, PharmD
Clinical Pharmacy Specialist, William S. Middleton Memorial
Veterans Hospital, Madison, Wisconsin
Human Immunodeficiency Virus: Treatment and Prevention
Albert P. Lin, MD
Assistant Professor, Ophthalmology, Baylor College of Medicine;
Staff Physician, Eye Care Line, Michael E. DeBakey Veterans
Affairs Medical Center, Houston, Texas
Glaucoma
Kevin Lin, MD
Department of Otolaryngology, Head and Neck Surgery, Baylor
College of Medicine, Houston, Texas
Contributors
Obstructive Sleep Apnea
Janet C. Lindemann, MD, MBA
Dean of Medical Student Education, Professor of Family
Medicine, University of South Dakota Sanford School of
Medicine, Sioux Falls, South Dakota
Fatigue
xv
Jeffrey A. Linder, MD, MPH
Chief, Division of General Internal Medicine and Geriatrics,
Michael A. Gertz Professor of Medicine, Northwestern
University Feinberg School of Medicine, Chicago, Illinois
Influenza
James Lock, MD, PhD
Professor of Psychiatry, Stanford University, Stanford, California
Eating Disorders
M. Chantel Long, MD
Clinical Assistant Professor, Department of Family and
Community Medicine, University of Kansas School of
Medicine–Wichita; Associate Director, Smoky Hill Family
Medicine Residency, Salina, Kansas
Condylomata Acuminata; Warts (Verrucae)
Colleen Loo-­Gross, MD, MPH
Assistant Professor, Department of Family & Community
Medicine, University of Kansas School of Medicine-­Wichita,
Wichita, Kansas
Amenorrhea
 Uma Malhotra, MD
Department of Medicine, Section of Infectious Diseases, Virginia
Mason Medical Center; Clinical Associate Professor, Infectious
Diseases, University of Washington, Seattle, Washington
Ebola Virus Disease
Emily Manlove, MD
Adjunct Clinical Assistant Professor, Family Medicine, IU Health
Southern Indiana Physicians, Bloomington, Indiana
Cough
JoAnn E. Manson, MD, DrPH
Chief, Division of Preventive Medicine, Department of Medicine,
Brigham and Women’s Hospital; Professor of Medicine,
Michael and Lee Bell Professor of Women’s Health, Harvard
Medical School, Boston, Massachusetts
Menopause
Meghna P. Mansukhani, MD
Associate Professor, Center for Sleep Medicine, Mayo Clinic and
Foundation, Mayo Clinic College of Medicine, Rochester,
Minnesota
Sleep Disorders
Claudio Marcocci, MD
Professor of Endocrinology, Department of Clinical and
Experimental Medicine, University of Pisa; Head, Endocrine
Unit 2, University Hospital of Pisa, Pisa, Italy
Hyperparathyroidism and Hypoparathyroidism
Curtis E. Margo, MD, MPH
Clinical Professor, Departments of Pathology and Cell Biology
and Ophthalmology, University of South Florida Morsani
College of Medicine, Tampa, Florida
Contributors
Dry Eye Syndrome; Uveitis
Jason E. Marker, MD, MPA
Associate Director, Memorial Hospital Family Medicine
Residency; Clinic Director, E. Blair Warner Family Medicine
Center, South Bend, Indiana
Neurofibromatosis (Type 1)
xvi
Paul Martin, MD
Chief, Gastroenterology and Hepatology, Mandel Chair in
Gastroenterology, University of Miami, Miami, Florida
Cirrhosis
Kristine Matson, MD, MPH
Clinical Associate Professor, Division of Infectious Diseases,
University of Wisconsin Hospital and Clinics, Madison,
Wisconsin
Travel Medicine
Mark A. Matza, MD, MBA
Department of Rheumatology, Massachusetts General Hospital,
Boston, Massachusetts
Polymyalgia Pneumatica and Giant Cell Arteritis
Pinckney J. Maxwell IV, MD
Associate Professor of Surgery, Division of Gastrointestinal and
Laparoscopic Surgery, Medical University of South Carolina,
Charleston, South Carolina
Tumors of the Colon and Rectum
Danica May, MD
Assistant Professor, Department of Urology, University of Kansas
Medical Center, Kansas City, Kansas
Malignant Tumors of the Urogenital Tract
Marshall Mazepa, MD
Department of Medicine, Division of Hematology, Oncology
and Transplantation, University of Minnesota Medical School,
Minneapolis, Minnesota
Porphyrias
Christopher McGrew, MD
Departments of Family and Community Medicine and Orthopedics
and Rehabilitation, Sports Medicine Division, University of New
Mexico Health Sciences Center, Albuquerque, New Mexico
Sports-­Related Head Injuries
Christopher C. McGuigan, MB, ChB, MPH
Consultant in Public Health Medicine, Health Protection, NHS
Fife, Cameron Hospital, Leven, Fife, United Kingdom
Psittacosis
Michael McGuigan, MD
Medical Director, Long Island Regional Poison and Drug Information
Center, Winthrop-­University Hospital, Mineola, New York
Medical Toxicology
Mick S. Meiselman, MD
Director of Advanced Therapeutic Endoscopy, Central Coast
Gastroenterology, San Luis Obispo, California
Calculous Biliary Disease
Moises Mercado, MD
Director, Experimental Endocrinology Unit, Hospital de
Especialidades, Centro Medico Nacional Siglo XXI, Institute
Mexicano del Seguro Social, Mexico City, Mexico
Acromegaly
Ryan Merrell, MD
Clinical Assistant Professor, Neurology, NorthShore University
HealthSystem, Evanston, Illinois
Brain Tumors
Steven L. Meyers, MD
Vice Chair, Quality and Informatics, Neurology, NorthShore
University Health System, Evanston, Illinois
Acute Facial Paralysis
Brian J. Miller, MD, PhD
Professor, Department of Psychiatry, Augusta University,
Augusta, Georgia
Schizophrenia
Timothy M. Millington, MD
Assistant Professor, Department of Surgery, Dartmouth-­
Hitchcock Medical Center, Lebanon, New Hampshire
Pleural Effusion and Empyema
Moben Mirza, MD
Associate Professor, Residency Program Director, Division of
Urologic Oncology, Department of Urology, University of
Kansas Medical Center, Kansas City, Kansas
Hematuria; Malignant Tumors of the Urogenital Tract
Kriti Mishra, MD
Department of Dermatology, University of New Mexico,
Albuquerque, New Mexico
Fungal Infections of the Skin
Howard C. Mofenson, MD
Professor of Pharmacology and Toxicology, New York College
of Osteopathic Medicine, Old Westbury, New York; Professor
of Pediatrics and Emergency Medicine, Stony Brook University
Medical Center School of Medicine, Stony Brook, New York
Medical Toxicology
Kris M. Mogensen, MS
Team Leader, Dietitian Specialist, Department of Nutrition,
Brigham and Women’s Hospital, Boston, Massachusetts
Parenteral Nutrition in Adults
Timothy I. Morgenthaler, MD
Professor of Medicine, Pulmonary and Critical Care Medicine;
Co-­Director, Center for Sleep Medicine, Mayo Clinic and
Foundation, Rochester, Minnesota
Sleep Disorders
Michael L. Moritz, MD
Professor of Pediatrics, Division of Nephrology, Department of
Pediatrics, The University of Pittsburgh School of Medicine,
Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Parenteral Fluid Therapy for Infants and Children
Rami Mortada, MD
Endocrine Center of Kansas, Wichita, Kansas
Diabetes Insipidus
Scott E. Moser, MD
Professor of Family and Community Medicine, Associate Dean
for Curriculum, University of Kansas School of Medicine–
Wichita, Wichita, Kansas
Attention-­Deficit/Hyperactivity Disorder
Heather E. Moss, MD, PhD
Assistant Professor, Departments of Ophthalmology &
Neurology and Neurological Sciences, Stanford University,
Stanford, California
Optic Neuritis
Judd W. Moul, MD
James H. Semans, MD Professor of Surgery, Urologic Surgery,
Duke University, Durham, North Carolina
Benign Prostatic Hyperplasia
Heidi E.K. Mullen, DO
Dermatology Resident, Department of Dermatology, HonorHealth/
Affiliated Dermatology, Scottsdale, Arizona
Contact Dermatitis
Natalia Murinova, MD
Clinical Associate Professor, Department of Neurology, University
of Washington, Seattle, Washington
Migraine
Michael Murphy, MD
Professor of Dermatology, University of Connecticut School of
Medicine; Attending Dermatopathologist, Department of
Dermatology, UConn Health, Farmington, Connecticut
Nevi
Diya F. Mutasim, MD
Professor of Dermatology and Pathology, University of Cincinnati
College of Medicine, Cincinnati, Ohio
Bullous Diseases
Arjun Muthusubramanian, MD, MPH
Physician, MedExpress Urgent Care, Richmond, Virginia
Bacterial Pneumonia
Alykhan S. Nagji, MD
Assistant Professor, Associate Program Director, Cardiothoracic
Surgery Residency Program, University of Kansas, Kansas
City, Kansas
Atelectasis
Moniba Nazeef, MD
Department of Medicine, Division of Hematology/Oncology,
University of Wisconsin School of Medicine and Public Health,
UW Carbone Cancer Center, Madison, Wisconsin
Venous Thromboembolism
Viswanathan K. Neelakantan, MD
Senior Professor of Medicine and Tropical Medicine, Sri Manakula
Vinayagar Medical College Hospital, Pondicherry, India
Foodborne Illnesses
Donald A. Neff, MD
Assistant Professor, Department of Urology, University of Kansas
School of Medicine, Kansas City, Kansas
Urinary Tract Infections in the Male
Tara J. Neil, MD
Associate Professor, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita;
Senior Associate Director, Via Christi Family Medicine
Residency, Wichita, Kansas
Postpartum Care
William G. Nelson, MD, PhD
Marion I. Knott Professor of Oncology, Director of the Sidney
Kimmel Comprehensive Cancer Center, The Johns Hopkins
University School of Medicine, Baltimore, Maryland
Prostate Cancer
David G. Neschis, MD
Clinical Associate Professor of Surgery, University of Maryland
School of Medicine, Baltimore, Maryland; Maryland Vascular
Center, Glen Burnie, Maryland
Aortic Disease: Aneurysm and Dissection
Contributors
Theresa Nester, MD
Medical Director of Integrated Transfusion Service Laboratories,
Bloodworks Northwest; Professor of Laboratory Medicine,
University of Washington Medical Center, Seattle, Washington
Blood Component Therapy and Transfusion Reactions
xvii
Tam T. Nguyen, MD
Clinician and Instructor, Family Medicine, Washington Township
Medical Group, Fremont, California; Assistant Clinical
Professor, Family and Community Medicine, University of
California, Davis, Sacramento, CA
Papulosquamous Eruptions
Andrea L. Nicol, MD, MSc
Associate Professor, Department of Anesthesiology, University of
Kansas School of Medicine, Kansas City, Kansas
Fibromyalgia
Lucybeth Nieves-­Arriba, MD
Assistant Professor, Gynecology Oncology, Zimmer Cancer
Center, Wilmington, North Carolina
Cancer of the Uterine Cervix
Andrei Novac, MD
Clinical Professor of Psychiatry, Director, Traumatic Stress
Program, University of California–Irvine School of Medicine,
Irvine, California
Depressive, Bipolar, and Related Mood Disorders
Enrico M. Novelli, MD
Associate Professor of Medicine, Chief, Section of Benign
Hematology, Director, Adult Sickle Cell Program, Department
of Medicine, Division of Hematology/Oncology, Vascular
Medicine Institute, Pittsburgh, Pennsylvania
Sickle Cell Disease
 Lauren Nye, MD
Assistant Professor of Internal Medicine, Division of Medical
Oncology, Breast Cancer Prevention and Survivorship
Research Center, University of Kansas Medical Center, Kansas
City, Kansas
Benign Breast Disease; Breast Cancer
Andrea T. Obi, MD
Section of Vascular Surgery, Department of Surgery, University
of Michigan, Ann Arbor, Michigan
Venous Thrombosis
Jeffrey P. Okeson, DMD
Professor and Interim Dean, Department of Oral Health Science,
University of Kentucky College of Dentistry, Lexington,
Kentucky
Temporomandibular Disorders
Carlos R. Oliveira, MD, PhD
Assistant Professor, Yale School of Medicine, Division of Pediatric
Infectious Diseases, Yale Child Health Research Center, New
Haven, Connecticut
Lyme Disease and Post-Treatment Lyme Disease Syndrome
Peck Y. Ong, MD
Associate Professor of Clinical Pediatrics, Keck School of
Medicine, University of Southern California/Children’s
Hospital Los Angeles, Los Angeles, California
Atopic Dermatitis
Daniel S. Oram, MD
Clinical Lecturer, Department of Family Medicine, Women’s
Health Fellow, Department of Obstetrics and Gynecology,
University of Michigan Medical School, Ann Arbor, Michigan
Contributors
Postpartum Depression
Gary D. Overturf, MD
Professor Emeritus, Departments of Pediatrics and Pathology,
University of New Mexico School of Medicine, Albuquerque,
New Mexico
Bacterial Meningitis
xviii
Bulent Ozgonenel, MD
Associate Professor in Pediatric Hematology/Oncology, Central
Michigan University, Children’s Hospital of Michigan, Wayne
State University, Detroit, Michigan
Hemophilia and Related Conditions
Karel Pacak, MD, PhD, DSc
Senior Investigator, Chief, Section on Medical Neuroendocrinology,
Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health, Bethesda,
Maryland
Pheochromocytoma
José A. Padin-­Rosado, MD
Associate Professor, Department of Neurology, University of
New Mexico School of Medicine, Albuquerque, New Mexico
Seizures and Epilepsy in Adolescents and Adults
Tanyatuth Padungkiatsagul, MD
Attending Physician, Department of Ophthalmology, Faculty
of Medicine, Ramathibodi Hospital, Mahidol University,
Bangkok, Thailand; Visiting Scholar, Department of
Ophthalmology, Stanford University, Palo Alto, California
Optic Neuritis
Heather L. Paladine, MD, MEd
Assistant Professor of Medicine at Columbia University Medical
Center, Center for Family and Community Medicine, Columbia
College of Physicians and Surgeons, New York, New York
Vulvovaginitis
John E. Pandolfino, MD
Hans Popper Professor of Medicine, Feinberg School of Medicine,
Northwestern University, Chicago, Illinois
Dysphagia and Esophageal Obstruction
Jotam Pasipanodya, MD
Research Scientist, University of Texas Southwestern Medical
Center at Dallas, Dallas, Texas
Tuberculosis and Other Mycobacterial Diseases
Pasquale Passarella, MD
Endocrinologist, Assistant Professor of Medicine at Albany
Medical Center, Albany, New York
Diabetic Ketoacidosis
Deval Patel, MD
Division of Hospital Pediatrics, Nemours Children’s Specialty
Care–Jacksonville; Associate Program Director, University of
Florida Pediatric Residency Training Program–Jacksonville,
Jacksonville, Florida
Parenteral Fluid Therapy for Infants and Children
Simon Patton, MD
Female Pelvic Medicine and Reconstructive Surgery, Via Christi
Health, Wichita, Kansas
Urinary Incontinence
Gerson Oliveira Penna, MD, PhD
Full Researcher, Tropical Medicine Center, University of Brasilia,
Fiocruz School of Government, Brasilia, Brazil
Leprosy
Maria Lucia Fernandes Penna, MD, PhD
Professor, Department of Epidemiology and Biostatistics, Federal
University Fluminense, Rio de Janeiro, Brazil
Leprosy
Allen Perkins, MD, MPH
Professor and Chair, Family Medicine, University of South
Alabama, Mobile, Alabama
Marine Poisonings, Envenomations, and Trauma
Leah Peterson, MD
Clinical Assistant Professor, Department of Family and
Community Medicine, University of Kansas School of
Medicine–Wichita, Wichita, Kansas; Smoky Hill Family
Medicine Residency, Salina, Kansas
Hypertension in Pregnancy
Georg A. Petroianu, MD, PhD
Professor & Chair, Department of Pharmacology & Therapeutics,
College of Medicine–Khalifa University, Abu Dhabi, United
Arab Emirates
Hiccups
Vesna M. Petronic-­Rosic, MD, MSc, MBA
Professor and Founding Chair, Department of Dermatology,
Georgetown University School of Medicine; Physician
Executive Director, Dermatolog, Washington, DC
Melanoma
Hanna Phan, PharmD
Clinical Associate Professor, Department of Clinical Pharmacy,
The University of Michigan College of Pharmacy; Clinical
Pharmacist Specialist, Ambulatory Care–Pediatric Cystic
Fibrosis, Michigan Medicine, C. S. Mott Children’s Hospital,
Ann Arbor, Michigan
Cystic Fibrosis
Mark Pietroni, MD, MBA
Medical Director, Gloucestershire Hospitals NHS Foundation
Trust, Gloucester, United Kingdom
Cholera
Susan M. Pollart, MD, MS
Ruth E. Murdaugh Professor, Family Medicine, University of
Virginia School of Medicine, Charlottesville, Virginia
Asthma in Children
Maria Araci de Andrade Pontes, MD, PhD
Associate Professor of Dermatology, State University of Ceará;
Dermatologist, Dona Libânia Center of Dermatology, Fortaleza,
Brazil
Leprosy
Andrew S.T. Porter, DO
Clinical Associate Professor, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita;
Director, University of Kansas School of Medicine–Wichita
Sports Medicine Fellowship, Wichita, Kansas
Common Sports Injuries
Charles R. Powell, MD
Associate Professor, Department of Urology, Indiana University
School of Medicine–Indianapolis, Indianapolis, Indiana
Prostatitis
Margaret Pusateri, MD
Emergency Medicine Physician, US Acute Care Solutions,
Pittsburgh, Pennsylvania
Sports-­Related Head Injuries
James M. Quinn, MD
Associate Program Director, Allergy/Immunology, San Antonio
Uniformed Service Health Education Consortium, San
Antonio, Texas; Associate Professor of Medicine, Uniformed
Services University of the Health Sciences, Bethesda, Maryland
Allergic Reactions to Insect Stings
Peter S. Rahko, MD
Professor of Medicine, Cardiovascular Medicine Division,
University of Wisconsin, Madison, Wisconsin
Mitral Valve Prolapse
S. Vincent Rajkumar, MD
Edward W. and Betty Knight Scripps Professor of Medicine,
Division of Hematology, Mayo Clinic, Rochester, Minnesota
Multiple Myeloma
David P. Rakel, MD
Professor and Chair, Department of Family and Community
Medicine, University of New Mexico School of Medicine,
Albuquerque, New Mexico
Infective Endocarditis
Kalyanakrishnan Ramakrishnan, MD
Professor, Department of Family and Preventive Medicine,
University of Oklahoma Health Sciences Center, Oklahoma
City, Oklahoma
Necrotizing Skin and Soft-­Tissue Infections
Julio A. Ramirez, MD
Professor of Medicine, University of Louisville School of
Medicine; Chief, Division of Infectious Diseases, Department
of Veterans Affairs Medical Center, Louisville, Kentucky
Legionellosis (Legionnaires’ Disease and Pontiac Fever)
Jatin Rana, MD
Assistant Professor of Medicine, Division of Hematology/Oncology,
College of Human Medicine, Michigan State University, East
Lansing, Michigan
Chronic Leukemias
Matthew A. Rank, MD
Associate Professor of Medicine, Division of Allergy, Asthma, and
Clinical Immunology, Mayo Clinic Alix School of Medicine,
Mayo Clinic, Scottsdale, Arizona
Asthma in Adolescents and Adults
Didier Raoult, MD, PhD
Unite de recherche sur les maladies infectieuses tropicales, Aix-­
Marseille Universite, Marseille, France
Q Fever
Alwyn Rapose, MD
Department of Infectious Diseases, Reliant Medical Group,
Worcester, Massachusetts; Assistant Professor, Department of
Medicine, University of Massachusetts, Worcester, Massachusetts
Toxic Shock Syndrome
Anita Devi K. Ravindran, MD
Faculty of Medicine, Atma Jaya Catholic University of Indonesia,
Jakarta, Indonesia
Foodborne Illnesses
Elizabeth Reddy, MD
Contributors
Assistant Professor of Infectious Disease, Upstate Medical,
University Hospital, Syracuse, New York
Intestinal Parasites
Ian R. Reid, MD
Distinguished Professor of Medicine and Endocrinology,
University of Auckland, Auckland, New Zealand xix
Paget’s Disease of Bone
Elissa Rennert-­May, MD, MSc
Clinical Lecturer, University of Calgary, Alberta Health Services
Calgary, Calgary, Alberta, Canada
Methicillin-­Resistant Staphylococcus aureus
Karl T. Rew, MD
Associate Professor of Family Medicine and Urology, University
of Michigan Medical School, Ann Arbor, Michigan
Erectile Dysfunction
Mona Rezapour, MD, MHS
Clinical Instructor, Gastroenterology, University of California,
Los Angeles, Los Angeles, California
Inflammatory Bowel Disease
Amanda Rhyne, MD
Clinical Assistant Professor, Department of Family and
Community Medicine, University of Kansas School of
Medicine–Wichita, Wichita, Kansas
Serum Sickness
Martha Riese, MD
Clinical Instructor, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita,
Wichita, Kansas
Varicella (Chickenpox)
 David C. Robbins, MD Heitor de Sá Gonçalves, MD, PhD
Bud and Sally Cray Professor of Medicine, Director, University of Associate Professor of Dermatology, State University of Ceará;
Kansas Diabetes Institute, Department of Medicine, University Dermatologist, Dona Libânia Center of Dermatology, Fortaleza,
of Kansas Medical School, Kansas City, Kansas Brazil
Diabetes Mellitus in Adults Leprosy

Amy Robertson, PharmD Adnan Said, MD, MS

Clinical Assistant Professor, Departments of Pharmacy Practice Associate Professor of Medicine, Gastroenterology, and
and Family and Community Medicine, University of Kansas Hepatology, University of Wisconsin School of Medicine
School of Pharmacy; Clinical Pharmacist, Wesley Family and Public Health; Chief, Gastroenterology and Hepatology,
Medicine Residency Program, Wichita, Kansas Director, Liver Transplant, William S. Middleton VAMC,
Serum Sickness Madison, Wisconsin
Nonalcoholic Fatty Liver Disease
Malcolm K. Robinson, MD
Associate Professor of Surgery, Harvard Medical School; Tomoko Sairenji, MD, MS
Associate Chair of Surgery for Clinical Operations, Director, Assistant Professor of Family Medicine, University of Washington,
Nutrition Support Service, Brigham and Women’s Hospital, Seattle, Washington
Boston, Massachusetts Acute Bronchitis and Other Viral Respiratory Infections
Parenteral Nutrition in Adults
Susan L. Samson, MD, PhD
William P. Roche, MD Associate Professor, Baylor College of Medicine, Houston, Texas
Neuromuscular Division, Emory University, Atlanta, Georgia Hyponatremia
Myasthenia Gravis
Carlos E. Sanchez, MD
Tessa E. Rohrberg, MD Interventional Cardiology, Structural Heart Disease, Cardiovascular
Assistant Professor, Family and Community Medicine, University Diseases, Riverside Methodist Hospital, Columbus, Ohio
of Kansas School of Medicine–Wichita, Wichita, Kansas Valvular Heart Disease
Delirium
Sandeep Sangodkar, DO, MS
Cardiology Specialists Medical Group; Assistant Professor
Candice Rose, MD, MS, RD of Clinical Medicine, University of California, Riverside;
Assistant Professor of Medicine, University of Kansas Medical
Riverside, California
Center, Section of Endocrinology, Kansas City, Kansas
Hypertrophic Cardiomyopathy
Diabetes Mellitus in Adults
Arelis Santana, MD, MPH
Contributors

Peter G. Rose, MD Assistant Professor, Division of Infectious Diseases, University of

Case Western Reserve University School of Medicine; Section New Mexico School of Medicine, Albuquerque, New Mexico
Head, Gynecologic Oncology, Women’s Health Institute, Salmonellosis
Cleveland Clinic, Cleveland, Ohio
Cancer of the Uterine Cervix
Ravi Sarode, MD
Director, Division of Transfusion Medicine and Hemostasis,
xx
Richard N. Rosenthal, MD Professor, Pathology and Internal Medicine (Hematology/
Professor of Psychiatry, Icahn School of Medicine at Mount Sinai, Oncology), UT Southwestern Medical Center, Dallas, Texas
New York, New York Thrombotic Thrombocytopenic Purpura
Alcohol Use Disorders
Michael Schatz, MD, MS
Stephen Ross, MD Department of Allergy, Kaiser Permanente; Clinical Professor,
Professor and Vice Chair, Department of Neurology, Penn State Department of Medicine, University of California San Diego
University, Hershey, Pennsylvania School of Medicine, San Diego, California
Nonmigraine Headache Asthma in Adolescents and Adults

Alan R. Roth, DO Alex Schevchuck, MD, MS

Chairman, Department of Family Medicine, Ambulatory Care Assistant Professor, Internal Medicine/Cardiology, University of
and Community Medicine, Jamaica Hospital Medical Center, New Mexico, Albuquerque, New Mexico
Queens, New York; Assistant Professor, Department of Family Tachycardias
and Social Medicine, Albert Einstein College of Medicine,
Bronx, New York Lawrence R. Schiller, MD
Fever Attending Physician, Gastroenterology Division, Baylor University
Medical Center, Dallas, Texas
Anne-­Michelle Ruha, MD Malabsorption
Chair, Department of Medical Toxicology, Banner–University
Medical Center Phoenix; Professor, Departments of Internal Kim Schoessow, OTD, OTR/L, SCLV
Medicine and Emergency Medicine, University of Arizona Assistant Professor of Occupational Therapy, Colorado State
College of Medicine–Phoenix, Phoenix, Arizona University, Fort Collins, Colorado
Spider Bites and Scorpion Stings Vision Rehabilitation

Kristen Rundell, MS, MD Sarina Schrager, MD, MS

Associate Professor, Department of Family Medicine, The Ohio Professor of Family Medicine, University of Wisconsin, Madison,
State University, Columbus, Ohio Wisconsin
Drug Hypersensitivity Reactions; Mumps Abnormal Uterine Bleeding
Dan Schuller, MD
Chair and Professor, Department of Internal Medicine–
Transmountain, Texas Tech University Health Sciences Center,
Paul L. Foster School of Medicine, Dallas, Texas
Lung Abscess; Pulmonary Hypertension
Amy Seery, MD
Assistant Professor, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita;
Associate Director of Pediatrics, Via Christi Family Medicine
Residency, Wichita, Kansas
Normal Infant Feeding
Steven A. Seifert, MD
Professor of Emergency Medicine, University of New Mexico
School of Medicine, Albuquerque, New Mexico
Venomous Snakebite
Jeffery D. Semel, MD
Head, Section of Infectious Diseases, NorthShore University
Healthsystem, Evanston, Illinois
Clostridioides difficile Colitis
Saeed Kamran Shaffi, MD, MS
Associate Professor, Internal Medicine/Nephrology, University of
New Mexico, Albuquerque, New Mexico
Primary Glomerular Diseases
Beejal Shah, MD
Endocrinologist, Bay Pines VA HealthCare System, Bay Pines,
Florida
Hyponatremia
Prediman K. Shah, MD
Shapell and Webb Chair in Clinical Cardiology, Director,
Oppenheimer Atherosclerosis Research Center and
Atherosclerosis Prevention and Treatment Center, Smidt Heart
Institute, Cedars-­Sinai Medical Center; Professor of Medicine,
University of California, Los Angeles, Cedars-­Sinai Medical
Center, Los Angeles, California
Acute Myocardial Infarction
Samir S. Shah, MD, MSCE
Professor, Department of Pediatrics, University of Cincinnati
College of Medicine; Director, Division of Hospital Medicine,
James M. Ewell Endowed Chair, Cincinnati Children’s
Hospital Medical Center, Cincinnati, Ohio
Viral Meningitis
Shenil Shah, MD
Cardiovascular Medicine, University of Wisconsin School of
Medicine and Public Health, Madison, Wisconsin
Mitral Valve Prolapse
Jamile M. Shammo, MD
Professor of Medicine and Pathology, Division of Hematology,
Oncology and Stem Cell Transplantation, Rush University
Medical Center, Chicago, Illinois
Myelodysplastic Syndromes
Eugene D. Shapiro, MD
Professor of Pediatrics (General Pediatrics) and Epidemiology
(Microbial Diseases), Vice Chair for Research, Department
of Pediatrics, Deputy Director, Investigative Medicine PhD
Program, Co-­Director of Education, Yale Center for Clinical
Investigation, New Haven, Connecticut
Lyme Disease and Post-Treatment Lyme Disease Syndrome
Ala I. Sharara, MD
Professor, Division of Gastroenterology, American University of
Beirut Medical Center, Beirut, Lebanon; Consulting Professor,
Duke University Medical Center, Durham, North Carolina
Bleeding Esophageal Varices
John P. Sheehan, MD
Department of Medicine, Division of Hematology/Oncology,
University of Wisconsin School of Medicine and Public Health,
UW Carbone Cancer Center, Madison, Wisconsin
Venous Thromboembolism
Kamille S. Sherman, MD
Assistant Professor, Family and Community Medicine, University
of North Dakota School of Medicine and Health Sciences,
Grand Forks, North Dakota
Sunburn
Sable Shew, MD
Department of Urology, Naval Medical Center San Diego, San
Diego, California
Urethral Stricture Disease
Karlynn Sievers, MD
Faculty Physician, St. Mary’s Family Medicine Residency, Grand
Junction, Colorado
Trigeminal Neuralgia
Hugh Silk, MD, MPH
Professor, Department of Family Medicine & Community Health,
UMass Medical School; Learning Communities Mentor,
Blackstone House; Part-­ time Lecturer, Harvard School of
Dental Medicine, Boston, Massachusetts; Medical Director,
Primary Care Wellness Center/Community, Healthlink Center
Contributors
for Integration of Primary Care and Oral Health, Worcester,
Massachusetts
Trigeminal Neuralgia; Diseases of the Mouth
Lisa Simon, MD, DMD
Fellow in Oral Health and Medicine Integration, Oral Health
Policy and Epidemiology, Harvard School of Dental Medicine,
Boston, Massachusetts xxi
Diseases of the Mouth
Aaron D. Sinclair, MD
Associate Professor, Department of Family and Community
Medicine, Wesley Family Medicine Residency, University of
Kansas School of Medicine–Wichita, Wichita, Kansas
Diverticula of the Alimentary Tract
Dawd S. Siraj, MD, MPH&TM
Professor of Medicine, Associate Program Director, Infectious
Diseases Fellowship, Director, Global Health Pathway,
Department of IM; Director, International Travel Clinic,
Division of Infectious Diseases, University of Wisconsin-
Madison, Madison, Wisconsin
Travel Medicine
Philip D. Sloane, MD, MPH
Elizabeth and Oscar Goodwin Distinguished Professor,
Co-­Director, Program on Aging, Disability, and Long-­Term
Care, Cecil G. Sheps Center for Health Services Research,
University of North Carolina, Chapel Hill, North Carolina
Alzheimer’s Disease
 Zachary L. Smith, DO José Antonio Suárez, MD
Division of Gastroenterology and Liver Disease, University Hospitals Clinic Research Unit, Instituto Conmemorativo Gorgas de
Digestive Health Institute; Assistant Professor of Medicine, Case Estudios de la Salud, Panama City, Panama
Western Reserve University School of Medicine, Cleveland, Ohio Malaria
Calculous Biliary Disease
Masayoshi Takashima, MD
John Sojka, MD Chairman, Department of Otolaryngology–Head and Neck
Associate Professor, Department of Orthopaedic Surgery, Surgery, Houston Methodist Hospital, Houston, Texas
University of Kansas Medical Center, Kansas City, Kansas Obstructive Sleep Apnea
Osteomyelitis
Varun Takyar, MD
William J. Somers, MD Staff Hepatologist, Department of GI/Liver, Sutter Health East
Urology Department, Veteran Affairs Ambulatory Care Center, Bay Medical Foundation, Berkeley, California
Columbus, Ohio Hepatitis A, B, D, and E
Nephrolithiasis
Carolina Talhari, MD, PhD
Mihae Song, MD Associate Professor of Dermatology, State University of
Assistant Professor, Department of Gynecologic Oncology, Rutgers Amazonas; Dermatologist, Alfredo da Matta Foundation for
Cancer Institute of New Jersey, New Brunswick, New Jersey Dermatology, Manaus, Amazonas, Brazil
Ovarian Cancer Leprosy

Nestor Sosa, MD Jie Tang, MD

Chief, Infectious Disease Division, Department of Internal Associate Professor, Division of Kidney Diseases and
Medicine, University of New Mexico School of Medicine, Hypertension, Alpert Medical School, Brown University,
Albuquerque, New Mexico Providence, Rhode Island
Malaria Hypokalemia and Hyperkalemia

Timothy Sowder, MD Jessica Tate, MD

Associate Professor, Department of Anesthesiology, University of Assistant Professor of Neurology, Wake Forest University School
Kansas School of Medicine, Kansas City, Kansas of Medicine, Winston-­Salem, North Carolina
Fibromyalgia Parkinson Disease

Linda Speer, MD Kim Templeton, MD

Professor and Chair, Family Medicine, University of Toledo, Professor of Orthopaedic Surgery, Department of Orthopaedic
Contributors

Toledo, Ohio Surgery, University of Kansas Medical Center, Kansas City,

Dysmenorrhea Kansas
Osteomyelitis
Abby L. Spencer, MD, MS
Vice Chair of Education–Medicine Institute, Associate Professor Joyce M.C. Teng, MD, PhD
of Medicine, Cleveland Clinic Lerner College of Medicine, Professor of Dermatology and Pediatrics, Stanford University
Cleveland, Ohio School of Medicine; Lucile Packard Children’s Hospital at
xxii Stanford, Stanford, California
Contraception
Urticaria and Angioedema
Todd Stephens, MD
Clinical Assistant Professor, Department of Family and Community Joanna Thomson, MD, MPH
Medicine, University of Kansas School of Medicine–Wichita; Pediatric Hospitalist, Cincinnati Children’s Hospital Medical
Associate Director, Via Christi Family Medicine Residency, Center; Associate Professor, Department of Pediatrics,
Wichita, Kansas University of Cincinnati College of Medicine, Cincinnati, Ohio
Genital Ulcer Disease: Chancroid, Granuloma Inguinale, and Viral Meningitis
Lymphogranuloma
J. Brantley Thrasher, MD
Executive Director, American Board of Urology, Charlottesville,
Erik Kent St. Louis, MD, MS Virginia
Associate Professor, Neurology, Mayo Clinic College of Medicine, Hematuria
Rochester, Minnesota
Sleep Disorders William Tillett, MBChB, PhD
Consultant Rheumatologist, Royal National Hospital for
Constantine A. Stratakis, MD, PhD Rheumatic Diseases; Senior Lecturer, Pharmacy and
Head, Section on Endocrinology and Genetics; Scientific Director, Pharmacology, University of Bath, Bath, United Kingdom
National Institute of Child Health and Human Development, Psoriatic Arthritis
National Institutes of Health, Bethesda, Maryland
Cushing’s Syndrome Kenneth Tobin, DO
Clinical Assistant Professor, Director, Chest Pain Center, University
Daniel Stulberg, MD of Michigan, Northville, Michigan
Professor and Vice Chair of Education, Department of Family Angina Pectoris
and Community Medicine, University of New Mexico School
of Medicine, Albuquerque, New Mexico
Premalignant Skin Lesions
Theodore T. Tsaltas, MD
Tri-­
Star Summit Medical Center, Hermitage, Tennessee; OB
Hospitalist Group, Chattanooga, Tennessee
Uterine Leiomyoma
Sebastian H. Unizony, MD
Assistant Professor of Medicine, Massachusetts General Hospital;
Instructor in Medicine, Massachusetts General Hospital
Rheumatology, Allergy and Immunology Division, Harvard
Medical School, Boston, Massachusetts
Polymyalgia Rheumatica and Giant Cell Arteritis
Mark Unruh, MD, MS
Chair, Department of Internal Medicine, University of New
Mexico School of Medicine, Albuquerque, New Mexico
Chronic Kidney Disease
Locke Uppendahl, MD
Clinical Instructor, Obstetrics and Gynecology, Division of
Gynecologic Oncology, University of Kansas School of
Medicine–Wichita, Wichita, Kansas
Cancer of the Endometrium
Anusha Vallurupalli, MBBS
Assistant Professor of Medicine, Division of Hematologic
Malignancies and Cellular Therapeutics, University of Kansas
Medical Center, Kansas City, Kansas
Hodgkin Lymphoma; Pernicious Anemia/Megaloblastic
Anemia
Donald C. Vinh, MD
Director, Infectious Disease Susceptibility Program, FRQS Clinician-­
Scientist, Associate Professor, Department of Medicine, Divisions
of Infectious Diseases and Allergy and Clinical Immunology,
Departments of Medical Microbiology and Human Genetics,
McGill University Health Centre–Research Institute, Montreal,
Quebec, Canada
Blastomycosis
Jatin M. Vyas, MD, PhD
Associate Professor of Medicine, Division of Infectious Disease,
Massachusetts General Hospital, Boston, Massachusetts
Rat-­Bite Fever
Tamara Wagner, MD
Associate Professor, Department of Pediatrics, Oregon Health &
Science University, Portland, Oregon
Bronchiolitis
Thomas W. Wakefield, MD
Stanley Professor of Surgery, Section of Vascular Surgery, Department
of Surgery, University of Michigan, Ann Arbor, Michigan
Venous Thrombosis
Arnold Wald, MD
Division of Gastroenterology and Hepatology, University of
Wisconsin School of Medicine and Public Health, Madison,
Wisconsin
Irritable Bowel Syndrome

George Van Buren II, MD Ellen R. Wald, MD

Associate Professor of Surgery, Michael E. DeBakey Department Chair, Department of Pediatrics, University of Wisconsin School
of Surgery, Baylor College of Medicine, Houston, Texas of Medicine and Public Health, Madison, Wisconsin
Acute and Chronic Pancreatitis Urinary Tract Infections in Infants and Children

Contributors
David van Duin, MD, PhD Robin A. Walker, MD
Associate Professor of Medicine, University of North Carolina, Northwest Family Physicians, Clinical Assistant Professor,
Chapel Hill, North Carolina Department of Family and Community Medicine, University
Histoplasmosis of Kansas School of Medicine–Wichita, Wichita, Kansas
Epididymitis and Orchitis
Daniel J. Van Durme, MD, MPH xxiii
Professor and Chair, Family Medicine and Rural Health, Florida Barry M. Wall, MD
State University College of Medicine, Tallahassee, Florida Professor of Medicine, Division of Nephrology, Veterans, Affairs
Acne Vulgaris; Rosacea Medical Center, University of Tennessee Health, Science
Center, Memphis, Tennessee
Elena V. Varlamov, MD Diabetic Ketoacidosis
Departments of Neurological Surgery and Medicine, Northwest
Pituitary Center, Oregon Health & Science University, Andrew Wang, MD
Portland, Oregon Professor of Medicine (Cardiology), Vice Chief for Clinical
Hypopituitarism Affairs, Division of Cardiology, Duke University Medical
Center, Durham, North Carolina
Christopher Vélez, MD Infective Endocarditis
Massachusetts General Hospital, Boston, Massachusetts
Dysphagia and Esophageal Obstruction Ernest Wang, MD
Clinical Professor of Emergency Medicine, Evanston Hospital,
Gregory Vercellotti, MD NorthShore University HealthSystem, Evanston, Illinois
Professor, Department of Medicine, University of Minnesota, Disturbances Due to Cold
Minneapolis, Minnesota
Porphyrias Jennifer Wang, DO
Assistant Professor, Critical Care Medicine, The Mount Sinai
Kyle Vincent, MD Hospital, New York, New York
Clinical Associate Professor, Department of Surgery, University Targeted Temperature Management (Therapeutic Hypothermia)
of Kansas School of Medicine–Wichita, Wichita, Kansas
Gastritis and Peptic Ulcer Disease Koji Watanabe, MD, PhD
Staff Doctor, AIDS Clinical Center, National Center for Global
Health and Medicine, Tokyo, Japan
Amebiasis
 Ruth Weber, MD, MSEd
Clinical Associate Professor, Department of Family and
Community Medicine, Medical University of South Carolina,
Charleston, South Carolina
Pharyngitis
Cheryl Wehler, MD
Assistant Professor, Department of Psychiatry and Behavioral
Sciences, University of Kansas School of Medicine–Wichita,
Wichita, Kansas
Panic Disorder
Alice C. Wei, MD, MSc
Associate Attending Surgeon, Memorial Sloan Kettering Cancer
Center; Associate Professor of Surgery, Weill Medical College
of Cornell University, New York, New York
Pancreatic Cancer
Jane A. Weida, MS, MD
Interim Department Chair, Director of Clinical Affairs, Professor,
Family, Internal and Rural Medicine, University of Alabama
College of Community Health Sciences, Tuscaloosa, Alabama
Measles (Rubeola)
David N. Weissman, MD
Director, Respiratory Health Division, National Institute for
Occupational Safety and Health, Morgantown, West Virginia
Pneumoconiosis: Asbestosis and Silicosis
Robert C. Welliver Sr., MD
Children’s Hospital Foundation Hobbs-­ Recknagel Endowed
Chair in Pediatrics, Professor of Pediatrics, Chief, Division
of Pediatric Infectious Diseases, The Children’s Hospital at
University of Oklahoma Health Sciences Center, Oklahoma
Contributors
City, Oklahoma
Viral Respiratory Infections
Rebecca M. Wester, MD
Adjunct Associate Professor, Family Medicine-­ Geriatrics,
University of Nebraska Medical Center, Omaha, Nebraska
Pressure Injury
xxiv
Ryan P. Westergaard, MD, PhD, MPH
Chief Medical Officer and State Epidemiologist for Communicable
Diseases, Wisconsin Department of Health Services, Associate
Professor, Division of Infectious Diseases, University of Wisconsin
School of Medicine and Public Health, Madison, Wisconsin
Human Immunodeficiency Virus: Treatment and Prevention
Randell Wexler, MD MPH
Professor, Vice Chair, Clinical Services, Department of Family
Medicine, The Ohio State University, Columbus, Ohio
Premature Beats
Brian M. Whitley, MD
Assistant Professor of Surgery, Division of Urology, Duke
University, Raleigh, North Carolina
Benign Prostatic Hyperplasia
Katarzyna Wilamowska, MD, PhD
Department of Family and Community Medicine, University of
New Mexico School of Medicine, Albuquerque, New Mexico
Premalignant Skin Lesions
Kimberly Williams, MD
Assistant Professor, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita,
Wichita, Kansas; Program Director, Smoky Hill Family
Medicine Residency, Salina, Kansas
Otitis Externa
Tracy L. Williams, MD
Associate Professor, Department of Family and Community
Medicine, University of Kansas School of Medicine–Wichita;
Via Christi Family Medicine Residency, Wichita, Kansas
Chlamydia trachomatis
Boris Winterhoff, MD
Assistant Professor, Obstetrics, Gynecology, and Women’s
Health, University of Minnesota, Minneapolis, Minnesota
Cancer of the Endometrium
Jennifer Wipperman, MD, MPH
Clinical Associate Professor, Department of Family and
Community Medicine, University of Kansas School of
Medicine–Wichita, Wichita, Kansas
Dizziness and Vertigo
Robert Wittler, MD
Professor of Pediatrics & Pediatric Infectious Diseases, University
of Kansas School of Medicine–Wichita, Wichita, Kansas
Tickborne Rickettsial Diseases (Rocky Mountain Spotted
Fever and Other Spotted Fever Group Rickettsioses,
Ehrlichioses, and Anaplasmosis)
Katherine I. Wolf, BS
Postbaccalaureate IRTA Fellow, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland
Pheochromocytoma
Gary S. Wood, MD
Professor and Founding Chair, Dean’s Chair in Cutaneous
Research, Geneva F. and Sture Johnson Professor Emeritus,
Department of Dermatology, University of Wisconsin–
Madison
Cutaneous T-­Cell Lymphomas, Including Mycosis Fungoides
and Sézary Syndrome
Scott Worswick, MD
Associate Clinical Professor of Dermatology, Keck Hospital of
the University of Southern California; Director of Inpatient
Dermatology, Los Angeles County Hospital; Co-­Program Director,
USC Dermatology Residency Program, Los Angeles, California
Stevens-­Johnson Syndrome and Toxic Epidermal Necrolysis
Steve W. Wu, MD
Associate Professor, University of Cincinnati College of Medicine;
Assistant Professor, Cincinnati Children’s Hospital Medical
Center, Cincinnati, Ohio
Gilles de la Tourette Syndrome
Hadley Wyre, MD
Assistant Professor of Urology, University of Kansas Medical
Center, Kansas City, Kansas
Urethral Stricture Disease
Steven J. Yakubov, MD
John H. McConnell Chair of Advanced Structural Heart Disease,
System Chief, OhioHealth Structural Heart Disease, Columbus,
Ohio
Valvular Heart Disease
Xinghong Yang, PhD
Infectious Diseases and Pathology, University of Florida, Gainesville,
Florida
Brucellosis
Kenneth S. Yew, MD, MPH James A. Yiannias, MD
Faculty, Gundersen Medical Foundation Family Medicine Residency Professor of Dermatology, Mayo Clinic, Scottsdale, Arizona
Program, Gundersen Medical Center, La Crosse, Wisconsin Contact Dermatitis
Tinnitus
Natawadee Young, MD
Yooni Yi, MD Adjunct Professor, Clinical Director, Family Medicine, AnMed
Assistant Professor, Department of Urology, University of Health Family Medicine Residency Program, Anderson, South
Michigan, Ann Arbor, Michigan Carolina
Trauma to the Genitourinary Tract Antepartum Care

Contributors
xxv
 Preface
We dedicated last year’s annual edition of this book to Joan Ryan,
the Content Development Specialist of a dozen editions of Conn’s
Current Therapy and many other texts published by Elsevier Press
during her 21 years of employment. Joan died peacefully at age 67
in Tewksbury, Massachusetts on March 26, 2020, surrounded by
her loving family after her courageous battle with cancer.
We had a wonderful time working with Joan. A content devel-
opment specialist “keeps the publication train running on time.”
Joan organized the entire 1400+ pages of Conn’s Current Ther-
apy, making sure that each of more than 300 chapters were per-
fectly written. Joan knew how to manage authors and editors.
She would encourage and cajole authors to get their manuscripts
in on time so we could meet the publication schedule. She would
give hints and she would give directives to make sure the process
was moving along. Because she had helped on many other books,
she could suggest new expert authors. She would ask if everything
was O.K. if an editor got behind in his reviews.
We enjoyed Joan’s New England perspective and we enjoyed
listening to her Boston accent. She had a great sense of humor.
Sometimes we would call her and, after looking at the caller ID,
she would answer “What now?!!” We would just laugh. She had
an unforgettable laugh. We would complain together when some-
thing didn’t go as planned and then celebrate when the book was
in print. Then, we would start to work on the next edition. She
loved reading, gardening, cooking, Boston sports, and her family
and friends.
We will miss Joan. Our sympathy goes out to all of her family
members and friends in New England and around the country.
This is the 73rd edition of Conn’s Current Therapy and we are
honored to be only the fourth and fifth editors of this renowned
book. We are proud that the 71st and 72nd editions of the book
have received critical acclaim and outstanding reviews. We believe
the 73rd edition is the best ever.
Every chapter has been reviewed and updated. Authors con-
tinue to be rotated. The book is available online and in print.
The online version has a user-­friendly search function. Call-­out
boxes, tables, and figures highlight important information. We
are incorporating more electronic links in the text that connect
the reader to apps and clinical prediction tools that can easily be
accessed in practice.
This edition has several newly written chapters that primary
care physicians should review soon after purchasing the book.
The chapter COVID-­19 is written by a practicing physician and
public health expert who actively treats patients with COVID-­19.
The chapter Diabetes Mellitus in Adults is written by one of our
country’s leading experts in diabetes and members of his team.
The chapter Chronic Leukemias updates practicing physicians on
new information about genetic pathogenesis and current treat-
ment. The current management of osteomyelitis is thoroughly
and concisely explained.
We greatly appreciate the exacting work of the editorial staff at
Elsevier. Kathryn “Katie” DeFrancesco is the new Content Devel-
opment Manager. We communicate almost daily with Katie and
she has been wonderfully helpful and organized. She has stepped
right in to help and has picked up the intricacies of the manu-
script management process. We appreciate her work more than
she will know.
Senior Content Strategist Charlotta Kryhl has helped us make
many improvements in the book. She and Sarah Barth, Publisher,
have worked hard to push the book forward and improve com-
munication between the editorial and production teams. The
copyeditors at Elsevier do wonderful work and we thank them
all. Kate Mannix, Senior Project Manager, organizes the book
in the final stages of production. Thank you, Kate, for your out-
standing work.
We want to thank the authors. Through the editing process, we
have made physician friends across the country and internation-
ally, even though we have only met some through e-­mail corre-
spondence. As we review and edit each chapter, we recognize the
talent, expertise, and devotion each author brings to his or her
work. We have consulted some of our subspecialty co-­authors
about patient problems we have experienced in practice.
Like Dr. Howard Conn, we spend many late nights and early
mornings working on the book. It is a labor of love. We appreci-
ate the understanding, tolerance, and support our families show
us as we work to make Conn’s Current Therapy a practical, use-
ful, and clinically valuable resource.
We would like to dedicate this edition of Conn’s Current Ther-
apy to pharmacy editor Miriam Chan, PharmD. Dr. Chan is a
vital member of the editorial team. She has served as the phar-
macy editor since 2003.
Dr. Chan is the Program Director of Medical Education Qual-
ity and Safety at OhioHealth in Columbus. She has published
in various peer-­reviewed journals and books. She is a frequent
speaker at both national and international conferences. She has
been the recipient of multiple teaching awards, including the
Family Medicine Educator of the Decade Award from the Ohio-
Health residents at Riverside Methodist Hospital in Columbus.
Dr. Chan has written chapters on drug hypersensitivity reac-
tions, new drugs, and popular herbs and nutritional supplements
for Conn’s Current Therapy. As the pharmacy editor, she verifies
each and every drug name, dosage, and formulation. She uses
footnotes to identify off-­label drug dosages and uses, as well as
availability of the drug. She makes sure that the book uses both
generic and brand names so that busy practicing physicians can
easily access the information. Dr. Chan has a keen eye for detail
and clarifies crucial information for better understanding. Her
dedication and expertise have been invaluable assets to establish-
ing Conn’s Current Therapy as an accurate and useful reference
for clinicians.
When asked to reminisce about her early work with the book,
Dr. Chan recalled, “Back then, the manuscripts were sent to me
by mail. I wrote comments regarding spelling or dosage on yellow
post-­it notes and placed them near the drug in question. I inserted
footnote symbols in pencil in the manuscript and then used a cus-
tom pre-­inked stamp for each specific footnote. Thank goodness
for the computer! Editing electronically is definitely more efficient
and changes don’t get missed.”
We very much appreciate our close working relationship with
Dr. Chan. Thank you, Miriam, for your fine work over the years.
We hope for many more!
Rick D. Kellerman, MD
David P. Rakel, MD
 1 Symptomatic Care Pending
Diagnosis
CHEST PAIN
Method of
William E. Cayley Jr., MD, MDiv
CURRENT DIAGNOSIS
• Initial evaluation of chest pain should include evaluation of
clinical stability, a concise history and physical, and a chest
x-­ray and electrocardiogram (ECG) unless the cause is clearly
not life threatening.
• Chest pain described as exertional, radiating to one or both
arms, similar to or worse than prior cardiac chest pain, or as-
sociated with nausea, vomiting, or diaphoresis indicates high
risk for acute coronary syndrome (ACS). ECG identifies ST-­
elevation myocardial infarction (STEMI); cardiac biomarkers
are essential for further evaluation of suspected chest pain in
the absence of STEMI.
• The Wells, Geneva, and Pisa clinical prediction rules as well as
the Pulmonary Embolism Rule-­out Criteria (PERC) can help to
stratify a patient’s risk of pulmonary embolism (PE).
• Aortic dissection is an uncommon cause of chest pain, but
patients with abrupt or instantaneous chest pain that is rip-
ping, tearing, or stabbing should be evaluated for dissection
with chest x-­ray, computed tomography (CT), or magnetic
resonance imaging (MRI).
• Esophageal rupture may be suspected in patients with pain,
dyspnea, and shock following a forceful emesis, and prompt
imaging with CT or esophagram is essential.
• Patients who have suspected tension pneumothorax and who
are clinically stable should have a chest x-­ray for confirmation
before needle decompression is attempted.
CURRENT THERAPY
• P atients with STEMI require urgent reperfusion, and those
with unstable angina or non–STEMI (NSTEMI) require admis-
sion for further monitoring and evaluation.
• Most patients with PE require admission for monitoring
and anticoagulation, although outpatient treatment may
be possible for low-­risk patients after initial evaluation and
anticoagulation.
• Prompt surgical consultation is required for patients with
confirmed or suspected aortic dissection or esophageal rup-
ture.
• Clinically unstable patients with suspected tension pneumo-
thorax need immediate needle decompression.
Epidemiology
Chest pain is the chief complaint in 1% to 2% of all outpa-
tient primary care visits. More than 50% of emergency depart-
ment (ED) visits for chest pain are due to serious cardiovascular
conditions such as ACS or PE, but these account for less than
15% of outpatient primary care encounters for chest pain, and
up to 15% of chest pain episodes never reach a definitive diag-
nosis. Other potentially life-­threatening etiologies for chest pain
include PE, dissecting aortic aneurysm (AA), esophageal rupture,
and tension pneumothorax. In outpatient primary care, the most
common causes of chest pain are musculoskeletal, gastrointesti-
nal, angina due to stable coronary artery disease (CAD), anxiety
or other psychiatric conditions, and pulmonary disease.
Initial Assessment
In initial evaluation of chest pain, it is important to obtain a clear
history of the onset and evolution of the pain, especially details such
as location, quality, duration, and aggravating or alleviating factors.
Initial physical examination should include vital signs, assessment of
the patient’s overall general condition, and examination of the heart
and lungs. If there are any clinical signs of instability (altered mental
status, hypotension, marked dyspnea, or other signs of shock), initial
stabilization and diagnosis must be addressed simultaneously, con-
sistent with current guidelines for emergency cardiovascular care.
Unless the history and physical examination suggest an obviously
nonthreatening cause of chest discomfort, most adults with chest
pain should at least have basic diagnostic testing with an ECG and
a chest x-­ray. Several clinical prediction rules are available to help
confirm or exclude some common causes of chest pain (Box 1).
Diagnosis and Treatment
Acute Coronary Syndrome
ACS includes acute myocardial infarction (MI) (ST-­segment ele- 1
vation and depression, Q wave and non–Q wave) and unstable
angina. Findings on the history and physical examination that
increase the likelihood of ACS include radiation of pain to the right
arm or shoulder, to both arms or shoulders, or to the left arm; pain
associated with exertion, diaphoresis, nausea, or vomiting; pain
described as pressure or as “worse than previous angina or similar
to a previous MI”; or the presence of hypotension or an S3 on car-
diac auscultation. Elements of the history and exam that decrease
the likelihood of ACS are pleuritic, positional, or sharp chest pain;
pain in an inframammary location; pain not associated with exer-
tion; pain lasting just seconds or lasting more than 24 hours; or
chest pain reproducible with palpation. The Marburg Heart Score
(MHS) and the Interchest Clinical Prediction Rule can both help
to exclude CAD in primary care patients with chest pain, and use
of the MHS when evaluating primary care patients with chest pain
has been shown to improve clinical diagnostic accuracy (Table 1).
Recent studies have demonstrated that the presence or absence of
typical cardiac risk factors (e.g., diabetes, hypertension, smoking,
high cholesterol, or family history) have little diagnostic value for
determining the likelihood of ACS in patients over 40 years of age.
An ECG should be obtained promptly for any patient with
suspected ACS. ST-­segment elevation in two or more contiguous
leads, or presumed new left bundle branch block, is diagnostic of
STEMI and requires urgent revascularization with thrombolysis
or angioplasty at an appropriate facility. Ischemic ST-­segment
depression more than 0.5 mm, dynamic T-­wave inversion with
chest discomfort, or transient ST-­segment elevation of 0.5 mm or
more is classified as unstable angina or NSTEMI. However, none
of these findings is sensitive enough that its absence can exclude

BOX 1  Clinical Prediction Rules for Evaluating Patients
with Chest Pain
Acute Coronary Syndrome
• Diagnosing cardiac ischemia with exercise treadmill testing:
Duke treadmill score: https://www.mdcalc.com/duke-­
treadmill-­score
• What is the risk of a major cardiac event in the next 6
weeks? HEART Score: https://www.mdcalc.com/heart-­score-­
major-­cardiac-­events.
• What is the risk of ACS in someone with chest pain?
Marburg Heart Score: https://www.mdcalc.com/marburg-­
heart-­score-­mhs
• What is the risk of ACS in someone with chest pain?
Interchest Clinical Prediction Rule: https://www.mdcalc.com/i
nterchest-­clinical-­prediction-­rule-­chest-­pain-­primary-­care
• Assesses long-­term risk in those with ACS: GRACE ACS risk
calculator: http://www.outcomes-­umassmed.org/grace/
• Estimates mortality for patients with unstable angina and
non-­ST elevation MI: TIMI risk score: http://www.timi.org/
Pneumonia
• Diehr diagnostic rule for pneumonia in adults with acute
I Symptomatic Care Pending Diagnosis
cough: http://www.soapnote.org/infectious/diehr-­rule/
Pulmonary Embolism
• Geneva score for predicting risk of pulmonary embolism:
https://www.mdcalc.com/geneva-­score-­revised-­pulmonary-­
embolism
• Pisa clinical model for predicting the probability of PE: https
://ebmcalc.com/PulmonaryEmbRiskPisaCXR.htm
• Wells scoring system for risk of pulmonary embolism:
https://www.mdcalc.com/wells-­criteria-­pulmonary-­embolism
• Pulmonary Embolism Rule-­out Criteria:
https://www.mdcalc.com/perc-­rule-­pulmonary-­embolism
Thoracic Aortic Dissection
Aortic Dissection Detection Risk Score (ADD-­RS):
https://www.mdcalc.com/aortic-­dissection-­detection-­risk-­score-­
add-­rs
2 findings that reliably diagnose or exclude PE, but three clinical
TABLE 1  Marburg Heart Score
FINDING POINTS
Woman >64 years, man >54 1 also the most mathematically complicated and depends on clini-
years
Known CAD, cerebrovascular 1 and chest x-­ray findings. The Wells rule (Table 2) is based on the
disease, or peripheral vascular
disease
Pain worse with exercise 1
Pain not reproducible with 1 the low-­probability category, 30% in the moderate-­probability
palpation
Patient assumes pain is cardiac 1 clinically suspected to be at low risk for PE (<15% pretest prob-
CAD, Coronary artery disease. Approximately 97% of patients with an MHS score
of 2 or less will not have CAD. Approximately 23% of patients with an MHS
score of 3 or more will have CAD.
Adapted from Haasenritter J, Bösner S, Vaucher P, Herzig L, Heinzel-­Gutenbrunner
M, Baum E, Donner-­Banzhoff N: Ruling out coronary heart disease in pri-
mary care: external validation of a clinical prediction rule, Br J Gen Pract
62(599):e415–e421, 2012. https://doi.org/10.3399/bjgp12X649106. http://ww
w.ncbi.nlm.nih.gov/pmc/articles/PMC3361121/.
MI, and patients whose chest pain is not low risk still require
further assessment for ACS.
In patients with high-­risk chest pain who do not have STEMI,
elevated cardiac biomarkers distinguish NSTEMI from unstable
angina. Cardiac troponins T and I are more sensitive for detecting
NSTEMI than creatine kinase (CK) or the MB isoform (CK-­MB).
High-­sensitivity troponins will be coming into use with an even
greater sensitivity (negative predictive values Σ 99.5%).
Initial management of NSTEMI includes hospital admission
for antiplatelet, antithrombin, and antianginal therapy. Patients
with unstable angina should also be hospitalized for observa-
tion, and those with either NSTEMI or unstable angina require
risk stratification using the Thrombolysis in Myocardial Infarc-
tion Study Group (TIMI) or Global Registry of Acute Coronary
Events (GRACE) risk scores (see Box 1). Patients with chest pain
suspicious for CAD but no definite initial diagnosis of STEMI or
NSTEMI on initial presentation are often admitted to hospital
for overnight observation and serial cardiac biomarker measure-
ments at 6 and 12 hours after symptom onset to “rule out MI.”
However, use of the History, EKG, Age, Risk factors, Troponin
(HEART), TIMI, or GRACE scores may help to determine who
is at sufficiently low risk of major adverse cardiac events to allow
discharge for close follow-­up, and recent evidence suggests that
the HEART score may outperform TIMI and GRACE in deter-
mining which patients are at low risk (see Box 1).
Patients at low risk for ACS or MI can usually defer further
testing unless there are other risk factors in their family or past
medical history markedly increasing the likelihood of CAD. Cur-
rent recommendations are that all other patients with chest pain
suggestive of CAD should have further noninvasive testing within
7 days; however, a recent study of 4181 patients in an ED chest
pain unit found that a reasonable alternative may be to test tro-
ponin levels twice over a 6-­hour interval, with no stress testing if
both values are normal. Patients who can exercise and have no
left-­bundle-­branch block, preexcitation, or significant resting ST-­
segment depression on an ECG can be evaluated with an exercise
stress ECG, and the Duke treadmill score can then be used to
further quantify cardiac risk (see Box 1). Patients with baseline
ECG abnormalities should have perfusion imaging performed
along with a stress ECG, and those who cannot exercise may be
evaluated with a pharmacologic stress or vasodilator test (e.g.,
dobutamine [Dobutrex]1 or adenosine [Adenocard]1). Patients at
high risk for CAD or those with NSTEMI should generally pro-
ceed directly to angiography, which enables definitive assessment
of the coronary artery anatomy.
Pulmonary Embolism
There are no individual symptoms or physical examination
prediction rules have all been validated for use in determining
likelihood of PE and therefore whether further testing is needed
(see Box 1). The Pisa rule may be the most accurate, but it is
cal, ECG, and x-­ray findings. The Geneva rule requires blood gas
simplest combination of history and examination findings, and a
comparison between the Wells and Geneva rules found that the
Wells rule has a lower failure rate. With the Wells and Geneva
prediction rules, the likelihood of PE is approximately 10% in
category, and 65% in the high-­probability category. If a patient is
ability) and meets all of the PERC (Table 3), the risk of PE is less
than 2% and no further testing is needed.
Routine tests done for patients with chest pain are not particu-
larly helpful in diagnosing or excluding PE. The chest x-­ray may
be abnormal, but findings that typically occur with PE (atelecta-
sis, effusion, or elevation of a hemidiaphragm) are nonspecific.
ECG signs of right ventricular strain (S wave in lead I, Q wave
and inverted T wave in lead III) may be helpful if present, but
their absence does not exclude PE. Hypoxia may be present, but
up to 20% of patients with PE have a normal alveolar-­arterial
oxygen gradient.
Additional tests recommended for evaluating patients with sus-
pected PE include D-­ dimer testing, compression ultrasonography,
ventilation-­perfusion scintigraphy, or CT angiography. The use of
1 Not FDA-approved for this indication.

TABLE 2  Simplified Wells Scoring System for Pulmonary
Embolism
CLINICAL FINDING SCORE
Symptoms of DVT 3.0
No alternative diagnosis more 3.0
likely than PE
Heart rate >100 beats/min 1.5
Immobilization greater than 1.5
3 days or surgery in past 4
weeks
Previous objectively diagnosed 1.5
DVT or PE
Hemoptysis 1.0
Malignancy 1.0
Probability of PE: <2 points = low, 2–6 points = moderate, >6 points
= high
DVT, Deep vein thrombosis; PE, pulmonary embolism.
Adapted from Miniati M, Bottai M, Monti S: Comparison of 3 clinical models
for predicting the probability of pulmonary embolism, Medicine (Baltimore)
84:107–114, 2005; Torbicki A, Perrier A, Konstantinides S, et al: ESC Commit-
tee for Practice Guidelines (CPG): Guidelines on the diagnosis and management
of acute pulmonary embolism, Eur Heart J 29:2276–315, 2008. http://eurheartj
.oxfordjournals.org/content/29/18/2276.long.
TABLE 3  Pulmonary Embolism Rule-­out Criteria
Criteria (Excludes PE if all criteria are met and pretest probability is
estimated at less than 15%)
Age <50 years
Heart rate <100 beats/min
Pulse oximetry on room air >95%
No unilateral leg swelling
No hemoptysis
No surgery or trauma in the last 4 weeks
No prior DVT or PE
No hormone use
DVT, Deep vein thrombosis; PE, pulmonary embolism.
Adapted from Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM:
Clinical criteria to prevent unnecessary diagnostic testing in emergency de-
partment patients with suspected pulmonary embolism, J Thromb Haemost
2(8):1247–1255, 2004. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1538-­
7836.2004.00790.x.
adjusted D-­dimer levels based on age or clinical setting has been stud-
ied, but none of these approaches has been standardized. Patients with
suspected high-­risk PE (i.e., those with shock or hypotension) should
have immediate CT angiography and treatment for PE if the CT is
positive, although an echocardiographic finding of right ventricu-
lar overload may be used to justify treatment for PE in the unstable
patient with high clinical suspicion for PE when CT angiography is
not available. Patients who have suspected PE and are not at high risk
(i.e., no shock or hypotension) and have a high clinical probability
(based on Wells, Geneva, or Pisa scoring) should also proceed directly
to CT, with appropriate treatment if the scan is positive. Patients with
a low clinical probability of PE (based on one of the validated clini-
cal prediction rules) do not need further D-­dimer testing or imaging.
Patients with intermediate clinical probability should initially have D-­
dimer testing; further testing or treatment for PE is unnecessary if the
D-­dimer is negative, and CT angiography should be performed if the
D-­dimer is positive.
Anticoagulation, with thrombolysis in high-­risk patients, is the
foundation of treatment for PE. Patients with shock or hypotension
are at high risk and require hemodynamic and respiratory support,
thrombolysis, or embolectomy, followed by appropriate attention
to anticoagulation. Normotensive patients with echocardiographic
evidence of right ventricular dysfunction or serologic evidence of
myocardial injury (no elevation of troponins or CK-­ MB) have
intermediate risk and should be admitted for anticoagulation. Nor-
motensive patients who have normal results on echocardiography
and testing for myocardial injury are at low risk and often may be
discharged early for management at home after initiation of anti-
coagulation. Anticoagulation for PE should be started at the time
of diagnosis. Apixaban (Eliquis) or rivaroxaban (Xarelto) may
be used without prior oral anticoagulation; alternatively, unfrac-
tionated heparin, low-­molecular-­weight heparin, or fondaparinux
(Arixtra) may be started and continued for 5 to 10 days with simul-
taneous initiation of dabigatran (Pradaxa), edoxaban (Savaysa or
Lixiana), or warfarin (Coumadin) titrated to maintain an interna-
tional normalized ratio (INR) between 2.0 and 3.0.
Thoracic Aortic Dissection
Thoracic aortic dissection is a much less common cause of chest
pain; prevalence estimates are 2 to 3.5 cases per 100,000 person-­
years. Up to 40% of patients die immediately, and 5% to 20%
die during or shortly after surgery. Risk factors for acute tho-
racic aortic dissection include hypertension, presence of a pheo-
chromocytoma, cocaine use, weightlifting, trauma or a rapid
deceleration event, coarctation of the aorta, and certain genetic
abnormalities. Pain due to acute aortic dissection is perceived as
abrupt and severe in 84% to 90% of cases, and more than 50%
of patients describe the pain as sharp or stabbing. No physical
findings are sensitive or specific for detecting aortic dissection
because approximately equal percentages of patients are hyper-
tensive or normotensive or have hypotension or shock. The most
common physical findings (a murmur of aortic insufficiency or a
pulse deficit) occur in less than half of patients.
In any patient with severe chest pain that is abrupt or instan-
taneous in onset or has a ripping, tearing, or stabbing quality,
Chest Pain
acute thoracic aortic dissection should be suspected. Physical
examination should assess for a pulse deficit, a systolic pres-
sure differential between limbs of greater than 20 mm Hg, a
focal neurologic deficit, or a new aortic regurgitation murmur.
It is also important to ask about a family history of connective
tissue disease (including Marfan syndrome), about any family
or personal history of aortic dissection or thoracic aneurysm, 3
and about any known aortic valve disease or recent aortic
interventions. D-­dimer testing has been proposed as a way to
screen for aortic dissection, but it is more important to obtain
prompt imaging and surgical intervention for those in whom
dissection is confirmed. A low-­risk Aortic Dissection Detection
Risk Score (ADD-­RS) can help to exclude the diagnosis of aor-
tic dissection, whereas patients with a high-­risk score require
further evaluation.
An ECG should be obtained in all patients with suspected aor-
tic dissection to exclude STEMI (which can manifest with similar
symptoms). In all low-­and intermediate-­risk patients, a prompt
chest x-­ray can help by either confirming an alternative diagno-
sis or confirming the presence of thoracic aortic disease. High-­
risk patients should have prompt imaging with CT or MRI, and
those who are in shock or clinically unstable may be evaluated
by bedside transesophageal echocardiography. If thoracic aortic
dissection is confirmed on imaging, urgent surgical consultation
is required. Medical therapy should be started with intravenous β
blockers. Patients with dissection of the ascending aorta require
urgent surgery, whereas those with descending thoracic aortic
dissection may be managed medically unless hypotension or other
complications develop.
Esophageal Rupture
Esophageal rupture, or Boerhaave syndrome, has a high mortal-
ity rate. Esophageal rupture is rare; the most common cause is
endoscopically induced injury, but it can happen in other settings
as well. Common misdiagnoses include perforated ulcer, MI, PE,
dissecting aneurysm, and pancreatitis. The “classic” presentation
 has been described as pain, dyspnea, and shock followed by
forceful emesis, but the history and physical are commonly non-
specific. Diagnosis most commonly is made by contrast esopha-
gram or CT scan of the chest.
Patients whose rupture is diagnosed less than 48 hours after
symptom onset should be treated surgically (especially if sepsis is
present) or endoscopically. Those who present more than 48 hours
after symptom onset may be considered for conservative treatment
with hyperalimentation, antibiotics, and nasogastric suction.
Tension Pneumothorax
Tension pneumothorax is relatively rare among patients presenting
with chest pain, but it is potentially life-­threatening if not treated
properly. Common symptoms and physical findings include chest
pain, respiratory distress, decreased ipsilateral air entry, and tachycar-
dia; hypoxia, tracheal deviation, and hypotension are less common.
Emergency needle decompression is usually recommended if ten-
sion pneumothorax is suspected, but this is ineffective in some cases
and is associated with risks to the patient of pain, bleeding, infection,
and cardiac tamponade. However, waiting for radiographic confir-
mation of the diagnosis is associated with up to a fourfold increase
in mortality due to delay in decompression of the pneumothorax.
Patients most likely to benefit from an immediate attempt at needle
decompression are those with an oxygen saturation below 92%
I Symptomatic Care Pending Diagnosis
patients presenting with acute dyspnea. One recent study also found
that point-­of-­care ultrasound (POCUS) may have high sensitivity
and specificity for diagnosing acute cardiogenic pulmonary edema.
A three-­ item questionnaire has been developed specifically to
assess for panic disorder among patients with chest pain referred for
cardiac evaluation (Table 5), and there is good evidence that psy-
chological interventions such as cognitive behavioral therapy (CBT)
and breathing exercises can improve chest pain symptoms for
patients with nonspecific chest pain who do not have CAD. How-
ever, even in patients with possible panic disorder, further cardiac
testing should be done if there are significant cardiac risk factors.
Gastrointestinal disease can cause chest pain, but the history
and physical examination are relatively inaccurate for diagnos-
ing or excluding serious gastrointestinal pathology. However, if
life-­threatening cardiovascular or pulmonary causes of chest pain
have been excluded, it is appropriate to try a short course of a
high-­dose proton pump inhibitor (omeprazole [Prilosec] 40 mg
twice daily,3 lansoprazole [Prevacid] 30 mg daily, or esomepra-
zole [Nexium] 40 mg twice daily3) to evaluate for undiagnosed
gastroesophageal reflux disease (GERD) as the cause of chest pain
(even for patients without typical GERD symptoms).
3 Exceeds
dosage recommended by the manufacturer.

while on oxygen, a decreased level of consciousness while on oxy-

gen, a systolic blood pressure less than 90 mm Hg, or a respiratory TABLE 4  Diehr Diagnostic Rule for Pneumonia in Adults
rate below 10 breaths/min. Patients without these signs of instabil- with Acute Cough
ity may be better managed by waiting for chest imaging to confirm SIGNS AND SYMPTOMS
or exclude the presence of a pneumothorax. Although plain chest
x-­rays have typically been used for diagnosing a pneumothorax, one FINDING POINTS
study has found that pleural ultrasound may have higher sensitivity. Rhinorrhea –2
Sore throat –1
Other Causes of Chest Pain
A patient with chest pain and cough, fever, egophony, or dullness Night sweats 1
to percussion might have pneumonia, but none of these individual
Myalgia 1
findings is specific enough to confirm the diagnosis. A large study
in 1984 developed a decision rule (Table 4) using seven clinical Sputum all day 1
findings to predict the likelihood of pneumonia. There is ongoing
Respiratory rate >25 2
debate over the reliability of pneumonia diagnosis based solely on
history and physical examination; chest x-­ray is usually considered Temperature >100°F 2
the reference standard. However, a recent Cochrane review found
Interpretation
two trials suggesting that routine chest radiography does not affect
4 the clinical outcomes in adults and children whose presentations
are suggestive of a lower respiratory tract infection. Thus, at least SCORE PROBABILITY OF PNEUMONIA
for clinically stable outpatients, treatment for pneumonia based on –3 5
appropriate clinical findings alone may be reasonable.
Heart failure alone is an uncommon cause of chest pain, but it may –1 12
accompany ACS or cardiac valve disease. A displaced apical impulse 0 21
and a prior history of CAD support this diagnosis, and because
virtually all patients with heart failure have exertional dyspnea, its 1 30
absence is very helpful in excluding this diagnosis. An abnormal 3 37
ECG and cardiomegaly on chest x-­ray can increase the likelihood
of heart failure among patients with chest pain, and B-­natriuretic Adapted from Cayley Jr WE: Diagnosing the cause of chest pain, Am Fam Physician
72:2012–2021, 2005. http://www.aafp.org/afp/2005/1115/p2012.html.
peptide (BNP) is now commonly used for detecting heart failure in

TABLE 5  Evaluation for Chest Pain from Panic Disorder

ITEM 0 1 2 3 4 5
When you are nervous, how often Never Rarely Half the time Usually Always
do you think “I am going to pass
out”?
During the last 7 days, including Not at all A little bit Moderately Quite a bit Extremely
today, how much have you been
bothered by pains in the chest?
To what degree is your chest pain None Mild Moderate Severe
tiring or exhausting?
Approximately 76% of patients with a score of 4 or less will not have panic disorder (PD). Approximately 71% of patients with a score of 5 or more will have PD.
Adapted from: Dammen T, Ekeberg O, Arnesen H, Friis S: The detection of panic disorder in chest pain patients, Gen Hosp Psychiatry 21(5):323–332, 1999. PubMed
PMID: 10572773. http://www.ncbi.nlm.nih.gov/pubmed/10572773.
 Chest wall pain can usually be diagnosed by history and exami-
nation if other etiologies have been excluded, and such pain is
more likely if the patient’s pain is reproducible by palpation.
Measurement of the sedimentation rate is not generally helpful in
making the diagnosis, although in unusual situations radiography
may be helpful.
References
Cao AM, Choy JP, Mohanakrishnan LN, et al: Chest radiographs for acute low-
er respiratory tract infections, Cochrane Database Syst Rev 12:CD009119,
2013.
Cayley Jr WE: Chest pain‐tools to improve your in-­office evaluation, J Fam Pract
63(5):246–251, 2014.
Cayley Jr WE: Diagnosing the cause of chest pain, Am Fam Physician 72:2012–
2021, 2005.
de Schipper JP, Pull terGunne AF, Oostvogel HJ, van Laarhoven CJ: Spontaneous
rupture of the oesophagus: Boerhaave’s syndrome in 2008. Literature review and
treatment algorithm, Dig Surg 26:1–6, 2009.
Eriksson D, Khoshnood A, Larsson D, et al: Diagnostic accuracy of history and
physical examination for predicting major adverse cardiac events within 30 days
in patients with acute chest pain, J Emerg Med pii: S0736-4679(19)30828-5,
2019, https://doi.org/10.1016/j.jemermed.2019.09.044.
Harskamp RE, Laeven SC, Himmelreich JC, et al: Chest pain in general
practice: a systematic review of prediction rules, BMJ Open 27;9(2):e027081,
2019.
Hendriksen JM, Geersing GJ, Lucassen WA, et al: Diagnostic prediction models
for suspected pulmonary embolism: systematic review and independent external
validation in primary care, BMJ 8(351):h4438, 2015.
Hiratzka LF, Bakris GL, Beckman JA et al: 2010 ACCF/AHA/AATS/ACR/ASA/
SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of
patients with Thoracic Aortic Disease: a report of the American College of
Cardiology Foundation/American Heart Association Task Force on Prac-
tice Guidelines. Circulation 121:e266–e369, 2010. Erratum in Circulation
2010;122(4):e410.
Kisely SR, Campbell LA, Yelland MJ, Paydar A: Psychological interventions for
symptomatic management of non-­specific chest pain in patients with normal
coronary anatomy, Cochrane Database Syst Rev 6:CD004101, 2015.
Leigh-­Smith S, Harris T: Tension pneumothorax‐time for a re-­think? Emerg Med
J 22:8–16, 2005.
McConaghy JR, Oza RS: Outpatient diagnosis of acute chest pain in adults, Am
Fam Physician 87(3):177–182, 2013.
Nienaber CA, Clough RE: Management of acute aortic dissection, Lancet
385(9970):800–811, 2015.
O’Connor RE, Al Ali AS, Brady WJ, et al: Part 9: acute coronary syndromes: 2015
American Heart Association guidelines update for cardiopulmonary resuscitation
and emergency cardiovascular care, Circulation 132(18 Suppl. 2):S483–S500,
2015.
Raja AS, Greenberg JO, Qaseem A, et al: Clinical Guidelines Committee of the
American College of Physicians. Evaluation of patients with suspected acute
pulmonary embolism: best practice advice from the clinical guidelines commit-
tee of the American College of Physicians, Ann Intern Med 163(9):701–711,
2015.
Reinhardt SW, Lin CJ, Novak E, Brown DL: Noninvasive cardiac testing vs
clinical evaluation alone in acute chest pain: a secondary analysis of the
ROMICAT-­II randomized clinical trial, JAMA Intern Med 178(2):212–219,
2018.
Swap CJ, Nagurney JT: Value and limitations of chest pain history in the evalua-
tion of patients with suspected acute coronary syndromes, JAMA 294:2623–2629,
2005.
Wong BC: Is proton pump inhibitor testing an effective approach to diagnose gas-
troesophageal reflux disease in patients with noncardiac chest pain?: a meta-­
analysis, Arch Intern Med 165(11):1222–1228, 2005.
CONSTIPATION
Method of
Melissa Gaines, MD
CURRENT DIAGNOSIS
• A lthough constipation is a benign process, it is important to
recognize signs of a serious condition.
• Classification of normal transit constipation, slow transit
constipation, or pelvic floor dysfunction guides therapy.
• Clinical testing has low benefit, but colonoscopy or imaging
can assess organic causes.
CURRENT THERAPY
• Initial therapy includes soluble dietary fiber to improve symp-
toms in chronic constipation.
• Osmotic laxatives are preferred while using stimulant laxa-
tives as rescue agents.
• Surgery is reserved for pelvic floor dysfunction after optimal
therapies have failed.
Epidemiology
Constipation is common, with a prevalence of 1.9% to 27.2%,
but the description of symptoms is variable. A thorough history
and focused physical examination aids diagnosis. Treatment is
directed toward relief of symptoms, alleviation of precipitating
factors, and prevention of recurrence. Although constipation is a
benign process, it is important to recognize concerning signs for a
more serious medical condition such as malignancy.
Risk Factors
Vulnerable populations include female, elderly, neurodegenera-
tive disease, low-­fiber diet, painful rectal disorders, hypothyroid-
ism, and diabetes mellitus.
Pathophysiology
With aging, there is decreased rectal compliance, diminished rec-
tal sensation, and decreased resting anal pressures, while colonic
transit time is preserved. Normal transit constipation is a com-
ponent of irritable bowel syndrome with normal transit time and
stool frequency. Slow transit constipation is a condition with
colonic dysmotility resulting from altered enteric nervous system.
Defecatory disorders include structural disturbances of the pelvic
floor. Pelvic floor dysfunction is the paradoxical contraction of
Constipation
the external anal sphincter and puborectalis muscles during def-
ecation. Secondary causes of constipation are listed in Table 1.
Prevention
Provide an environment of privacy and comfort to allow for
natural defecation. Prescribe an adequate fluid and fiber intake
with specific amounts that vary depending on the patient’s condi-
5
tion. Encourage physical activity, with a low to moderate level
of exercise depending on the patient’s functional status. Develop
a routine for defecation with a prompt response to a call to def-
ecate urgently. Recurrent fecal impaction can be prevented with
polyethylene glycol (PEG, MiraLAX).
Clinical Manifestations
Patients will complain using qualitative terms of hard stools, a
feeling of incomplete voiding, straining, prolonged time for laxa-
tion, the need for additional maneuvers, abdominal bloating, and
abdominal pain (Table 2). A change in bowel habit differentiates
the current complaint from a serious medical condition. Red flags
include acute onset, weight loss, abdominal pain or cramping,
rectal bleeding, nausea or vomiting, rectal pain, fever, or a change
in stool caliber. Infants with abdominal distension and failure to
pass meconium within 24 hours indicate Hirschsprung disease.
Patients should be asked if they have had loose stools or bowel
incontinence to assess for fecal impaction. A medication review
is required (see Table 1). Classification of patients with normal
transit constipation, slow transit constipation, or pelvic floor dys-
function/defecatory disorders guides therapy.
Diagnosis
Diagnostic criteria have been established because the symptoms
can vary (see Table 2). Conduct a physical examination that
includes an assessment of vital signs, weight, volume status,
auscultation of bowel sounds, abdominal percussion for tym-
pani, and abdominal palpation for tenderness or mass. A rectal
 Chest wall pain can usually be diagnosed by history and exami-
nation if other etiologies have been excluded, and such pain is
more likely if the patient’s pain is reproducible by palpation.
Measurement of the sedimentation rate is not generally helpful in
making the diagnosis, although in unusual situations radiography
may be helpful.
References
Cao AM, Choy JP, Mohanakrishnan LN, et al: Chest radiographs for acute low-
er respiratory tract infections, Cochrane Database Syst Rev 12:CD009119,
2013.
Cayley Jr WE: Chest pain‐tools to improve your in-­office evaluation, J Fam Pract
63(5):246–251, 2014.
Cayley Jr WE: Diagnosing the cause of chest pain, Am Fam Physician 72:2012–
2021, 2005.
de Schipper JP, Pull terGunne AF, Oostvogel HJ, van Laarhoven CJ: Spontaneous
rupture of the oesophagus: Boerhaave’s syndrome in 2008. Literature review and
treatment algorithm, Dig Surg 26:1–6, 2009.
Eriksson D, Khoshnood A, Larsson D, et al: Diagnostic accuracy of history and
physical examination for predicting major adverse cardiac events within 30 days
in patients with acute chest pain, J Emerg Med pii: S0736-4679(19)30828-5,
2019, https://doi.org/10.1016/j.jemermed.2019.09.044.
Harskamp RE, Laeven SC, Himmelreich JC, et al: Chest pain in general
practice: a systematic review of prediction rules, BMJ Open 27;9(2):e027081,
2019.
Hendriksen JM, Geersing GJ, Lucassen WA, et al: Diagnostic prediction models
for suspected pulmonary embolism: systematic review and independent external
validation in primary care, BMJ 8(351):h4438, 2015.
Hiratzka LF, Bakris GL, Beckman JA et al: 2010 ACCF/AHA/AATS/ACR/ASA/
SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of
patients with Thoracic Aortic Disease: a report of the American College of
Cardiology Foundation/American Heart Association Task Force on Prac-
tice Guidelines. Circulation 121:e266–e369, 2010. Erratum in Circulation
2010;122(4):e410.
Kisely SR, Campbell LA, Yelland MJ, Paydar A: Psychological interventions for
symptomatic management of non-­specific chest pain in patients with normal
coronary anatomy, Cochrane Database Syst Rev 6:CD004101, 2015.
Leigh-­Smith S, Harris T: Tension pneumothorax‐time for a re-­think? Emerg Med
J 22:8–16, 2005.
McConaghy JR, Oza RS: Outpatient diagnosis of acute chest pain in adults, Am
Fam Physician 87(3):177–182, 2013.
Nienaber CA, Clough RE: Management of acute aortic dissection, Lancet
385(9970):800–811, 2015.
O’Connor RE, Al Ali AS, Brady WJ, et al: Part 9: acute coronary syndromes: 2015
American Heart Association guidelines update for cardiopulmonary resuscitation
and emergency cardiovascular care, Circulation 132(18 Suppl. 2):S483–S500,
2015.
Raja AS, Greenberg JO, Qaseem A, et al: Clinical Guidelines Committee of the
American College of Physicians. Evaluation of patients with suspected acute
pulmonary embolism: best practice advice from the clinical guidelines commit-
tee of the American College of Physicians, Ann Intern Med 163(9):701–711,
2015.
Reinhardt SW, Lin CJ, Novak E, Brown DL: Noninvasive cardiac testing vs
clinical evaluation alone in acute chest pain: a secondary analysis of the
ROMICAT-­II randomized clinical trial, JAMA Intern Med 178(2):212–219,
2018.
Swap CJ, Nagurney JT: Value and limitations of chest pain history in the evalua-
tion of patients with suspected acute coronary syndromes, JAMA 294:2623–2629,
2005.
Wong BC: Is proton pump inhibitor testing an effective approach to diagnose gas-
troesophageal reflux disease in patients with noncardiac chest pain?: a meta-­
analysis, Arch Intern Med 165(11):1222–1228, 2005.
CONSTIPATION
Method of
Melissa Gaines, MD
CURRENT DIAGNOSIS
• A lthough constipation is a benign process, it is important to
recognize signs of a serious condition.
• Classification of normal transit constipation, slow transit
constipation, or pelvic floor dysfunction guides therapy.
• Clinical testing has low benefit, but colonoscopy or imaging
can assess organic causes.
CURRENT THERAPY
• Initial therapy includes soluble dietary fiber to improve symp-
toms in chronic constipation.
• Osmotic laxatives are preferred while using stimulant laxa-
tives as rescue agents.
• Surgery is reserved for pelvic floor dysfunction after optimal
therapies have failed.
Epidemiology
Constipation is common, with a prevalence of 1.9% to 27.2%,
but the description of symptoms is variable. A thorough history
and focused physical examination aids diagnosis. Treatment is
directed toward relief of symptoms, alleviation of precipitating
factors, and prevention of recurrence. Although constipation is a
benign process, it is important to recognize concerning signs for a
more serious medical condition such as malignancy.
Risk Factors
Vulnerable populations include female, elderly, neurodegenera-
tive disease, low-­fiber diet, painful rectal disorders, hypothyroid-
ism, and diabetes mellitus.
Pathophysiology
With aging, there is decreased rectal compliance, diminished rec-
tal sensation, and decreased resting anal pressures, while colonic
transit time is preserved. Normal transit constipation is a com-
ponent of irritable bowel syndrome with normal transit time and
stool frequency. Slow transit constipation is a condition with
colonic dysmotility resulting from altered enteric nervous system.
Defecatory disorders include structural disturbances of the pelvic
floor. Pelvic floor dysfunction is the paradoxical contraction of
Constipation
the external anal sphincter and puborectalis muscles during def-
ecation. Secondary causes of constipation are listed in Table 1.
Prevention
Provide an environment of privacy and comfort to allow for
natural defecation. Prescribe an adequate fluid and fiber intake
with specific amounts that vary depending on the patient’s condi-
5
tion. Encourage physical activity, with a low to moderate level
of exercise depending on the patient’s functional status. Develop
a routine for defecation with a prompt response to a call to def-
ecate urgently. Recurrent fecal impaction can be prevented with
polyethylene glycol (PEG, MiraLAX).
Clinical Manifestations
Patients will complain using qualitative terms of hard stools, a
feeling of incomplete voiding, straining, prolonged time for laxa-
tion, the need for additional maneuvers, abdominal bloating, and
abdominal pain (Table 2). A change in bowel habit differentiates
the current complaint from a serious medical condition. Red flags
include acute onset, weight loss, abdominal pain or cramping,
rectal bleeding, nausea or vomiting, rectal pain, fever, or a change
in stool caliber. Infants with abdominal distension and failure to
pass meconium within 24 hours indicate Hirschsprung disease.
Patients should be asked if they have had loose stools or bowel
incontinence to assess for fecal impaction. A medication review
is required (see Table 1). Classification of patients with normal
transit constipation, slow transit constipation, or pelvic floor dys-
function/defecatory disorders guides therapy.
Diagnosis
Diagnostic criteria have been established because the symptoms
can vary (see Table 2). Conduct a physical examination that
includes an assessment of vital signs, weight, volume status,
auscultation of bowel sounds, abdominal percussion for tym-
pani, and abdominal palpation for tenderness or mass. A rectal
 Treatment
TABLE 1  Causes of Constipation
Nonpharmacologic therapies have limited benefit. Unless there
Dietary Low-­fiber diet, dementia, depression, anorexia, are signs of dehydration, increasing fluid intake is not indicated.
dehydration Moderate-­ intensity exercise improves symptoms of irritable
bowel syndrome. Probiotics are not beneficial.
Metabolic Diabetes mellitus, hypercalcemia, hypokalemia, There is moderate evidence for pharmacologic agents (Table 3).
hypothyroidism, systemic sclerosis
Normal transit constipation responds to soluble dietary fiber sup-
Neurologic Parkinson disease, spinal cord disorder, multiple plements (e.g., psyllium [Metamucil]); however, these should not
sclerosis, cerebrovascular disease (stroke) be used in the case of slow transit constipation or drug-­induced
Iatrogenic Antacids, iron, anticholinergics, antidepressants,
constipation. Osmotic agents with PEG (MiraLAX) or lactulose
antipsychotics, opiates, antiepileptics (Chronulac) can be dose increased for soft stools. Stimulant laxa-
tives are used as rescue therapy if patients do not have a bowel
Painful anorectal Anal fissure, hemorrhoids, abscess, fistula, pelvic movement for 2 days.
condition floor dysfunction, malignancy New classes of drugs to manage constipation include intesti-
nal secretagogues, serotonin 5-­ HT4 receptor antagonists, and
opiate antagonists. Lubiprostone (Amitiza) requires a negative
pregnancy test with contraception. Linaclotide (Linzess) is a 14–
TABLE 2  Rome III Criteria amino acid peptide similar to heat-­stable enterotoxins that cause
diarrhea. Lubiprostone and linaclotide are US Food and Drug
More than two present: Administration (FDA)-­approved for chronic idiopathic constipa-
1. Straining in more than 25% of defecations tion (CIC) and irritable bowel syndrome with constipation (IBS-­
2. Hard or lumpy stool in more than 25% of defecations C). Lubiprostone is also indicated for treatment of opioid-­induced
3. Sensation of incomplete evacuation constipation (OIC). Plecanatide (Trulance) is an approved drug
4. Sensation of anorectal blockage for treatment of CIC and IBS-­C in adults. It is a guanylate cyclase-
I Symptomatic Care Pending Diagnosis

5. Manual maneuvers
6. Fewer than three defecations per week
Loose stools are rare without laxative use
Insufficient criteria for irritable bowel syndrome
Symptoms for 3 months with onset 6 months before diagnosis
examination can detect resting rectal tone, fecal impaction, ano-
rectal disorders, or rectal mass. Defecatory disorders show an
increased resistance to the insertion of the examiner’s finger with
an impaired relaxation of the sphincter complex and reduced
perineal descent during a Valsalva maneuver. Conduct labora-
tory testing on electrolytes, hemoglobin, thyroid-­ stimulating
hormone, and fecal occult after initial measures fail. Red flag
symptoms require imaging with computed tomography (CT) of
the abdomen and pelvis or an endoscopy to diagnose malignancy
6 or fecal impaction. Anorectal testing with manometry and a rec-
tal balloon expulsion test is appropriate for pelvic floor dysfunc-
tion or defecatory disorders. Hirschsprung disease is diagnosed
with barium enema, rectal manometry, or a rectal suction biopsy.
Colonic transit rates with radiopaque markers (Sitz) on serial
abdominal radiographs over 4 to 7 days diagnose slow transit
constipation disorders.
­C agonist that increases fluid secretion into the upper intestine.
Methylnaltrexone (Relistor) and naloxegol (Movantik) are opi-
ate receptor antagonists that can cause laxation in patients on
chronic opiate therapy with number needed to treat (NNT) of 5.
Pelvic floor dysfunction or defecatory disorders respond to
biofeedback therapy by using manometry and visual or audi-
tory feedback. Patients practice expelling a balloon and improve
pelvic floor muscle coordination with Kegel exercises. Surgical
intervention with subtotal colectomy with ileorectal anastomosis
is indicated for slow transit constipation or defecatory disorders
after failure of optimal medical management.
Complications
Fecal impaction is a complication and a large bowel obstruction
with colonic perforation has high mortality. Pediatric and geriat-
ric patients are most susceptible with signs and symptoms of fecal
incontinence, abdominal pain, abdominal distention, anorexia,
weight loss, and delirium. Treatments for adults include a large-­
volume tap-­ water enema (500 to 1000 mL), local anesthetics
administered topically with abdominal massage, a colonoscopy,
or surgery. The prevention of recurrence requires maintenance
bowel regimen with osmotic agents such as PEG (MiraLAX).

TABLE 3  Drug Dosing and Adverse Effects

MECHANISM OF
CLASS DRUG NAME (BRAND) ADULT DOSING ACTION TIME TO ONSET (H) ADVERSE EFFECT
Fiber Bran 1 cup/day Increase water content Unknown Bloating excessive gas
Psyllium (Metamucil) 1 tsp and bulk of stool
Methylcellulose (Citrucel) 1 tbsp or 1 tab twice decreasing transit
Calcium polycarbophil daily time
(FiberCon) 2–4 tabs/day
Hyperosmolar Sorbitol 70% 15–30 mL twice daily Disaccharide 24–48 Sweet tasting,
agent Lactulose (Chronulac) metabolized by transient
colonic bacteria into abdominal cramps,
acetic acid and short-­ flatulence
chain fatty acids
Hyperosmolar PEG-­ES (GoLytely,1 8–32 oz daily Osmotic effect 0.5–1 Incontinence
agent CoLyte1) 17 g (1 tbsp) qd increasing
PEG (MiraLAX) intraluminal fluids
 TABLE 3  Drug Dosing and Adverse Effects—cont’d
CLASS DRUG NAME (BRAND) ADULT DOSING
Guanylate Plecanatide (Trulance) CIC and IBS-­C: 3 mg
cyclase-­C Linaclotide (Linzess) once daily
agonist CIC: 72–145 mcg
once daily
IBS-­C: 290 mcg once
daily
Chloride Lubiprostone (Amitiza) CIC and OIC: 24 mcg
channel twice daily
activator IBS-­C in women ≥18
y: 8 mcg twice daily
Stimulant Glycerin suppository 1 daily
Bisacodyl (Dulcolax) 10 mg suppository
Senna (Senokot, Perdiem) or 5–10 mg PO 3
Senna/docusate (Peri-­Colace) times a week
2–4 tabs twice daily
Enemas Mineral oil retention enema 199–250 mL daily PR
Tap water enema 500–1000 mL PR
Sodium phosphate enema 1 unit PR
(Fleet)
Opioid Methylnaltrexone (Relistor) 8–12 mg 1 dose SC
antagonist every other day as
needed for OIC
with advanced
illness.
450 mg PO once daily
or 12 mg SC once
daily for OIC with
chronic noncancer
pain.
Opioid Naloxegol (Movantik) 12.5–25 mg PO daily
antagonist
1Not US Food and Drug Administration (FDA) approved for this indication.
MECHANISM OF
ACTION TIME TO ONSET (H) ADVERSE EFFECT
Osmotic effect Cannot be calculated Diarrhea
increasing Abdominal pain,
intraluminal fluids, diarrhea
increase transit time
Increase intestinal Unknown Headache, nausea,
fluid secretion and diarrhea
improve fecal transit
Local rectal 8–12 Degeneration of
stimulation, Meissner and
secretory and Auerbach plexus
prokinetic effect
Evacuation induced by 6–8 for a mineral oil Mechanical trauma,
distended colon and enema incontinence, rectal
mechanical lavage 5–15 min for all damage
other enemas
Opioid mu receptor 4 Diarrhea, intestinal
antagonist in gut perforation
decreasing transit
time
Same as Relistor 6–36 Abdominal pain,
opioid withdrawal
reported

Cough
CIC, Chronic idiopathic constipation; IBS-­C, irritable bowel syndrome with constipation; OIC, opioid-­induced constipation; PEG-ES, polyethylene glycol and electrolyte
solution; PO, by mouth; PR, per rectum; SC, subcutaneously.

7
References COUGH
Arshad A, Powell C: Easily missed? Hirschsprung’s disease, Br Med J 345:e5521,
2012. Method of
Barish DF, Crozier RA, Griffin PH: Long-­term treatment with plecanatide was safe Emily Manlove, MD
and tolerable in patients with irritable bowel syndrome with constipation, Curr
Med Res Opin 1–5, 2018.
Bharucha AE, Pemberton JH, Locke GR: American Gastroenterological Association
technical review on constipation, Gastroenterology 144:218–238, 2013.
Gallagher PF, O’Mahony D, Quigley EM: Management of chronic constipation in
the elderly, Drugs Aging 25:807–821, 2008. CURRENT DIAGNOSIS
Gastroenterology: Rome criteria. Available at http://www.romecriteria.org/.
Higgins PD, Johanson JF: Epidemiology of constipation in North America: a system-
atic review, Am J Gastroenterol 99:750–759, 2004. • A
 cute Cough
Larkin PJ, Sykes NP, Centeno C, et al: The management of constipation in palliative • Noninfectious
care: Clinical practice recommendations, Palliat Med 22:796–807, 2008. • Chronic obstructive pulmonary disease exacerbation
McCallum IJ, Ong S, Mercer-­Jones M: Chronic constipation in adults, Br Med J
• Asthma exacerbation
338:b831, 2009.
Nee J, et al: Efficacy of treatments for opioid-­induced constipation: a systemic re- • Congestive heart failure exacerbation
view and meta-­analysis, Clin Gastroenterol Hepatol, 2018 Jan 25. • Pulmonary embolism
Schoenfeld P, et al: Low-­Dose linaclotide (72ug) for chronic idiopathic constipation: • Infectious
A 12-­week, randomized, double-­blind, placebo-­controlled trial, Am J Gastroen-
• Viral rhinosinusitis (the common cold)
terol, 2018, 113-105–114. https://doi.org/10.1038/ajg.2017.230.
Thomas J, Karver S, Cooney GA, et al: Methylnaltrexone for opioid-­induced consti- • Acute bacterial sinusitis
pation in advanced illness, N Engl J Med 358:2332–2343, 2008. • Acute bronchitis (chest cold)
Wald A: Management and prevention of fecal impaction, Curr Gastroenterol Rep • Pneumonia
10:299–501, 2008.
• Pertussis (whooping cough)
Wald A: Constipation: Advances in diagnosis and treatment, JAMA 315(2):185–
191, 2016 Jan 12. • Bronchiolitis (infants)
 TABLE 3  Drug Dosing and Adverse Effects—cont’d
CLASS DRUG NAME (BRAND) ADULT DOSING
Guanylate Plecanatide (Trulance) CIC and IBS-­C: 3 mg
cyclase-­C Linaclotide (Linzess) once daily
agonist CIC: 72–145 mcg
once daily
IBS-­C: 290 mcg once
daily
Chloride Lubiprostone (Amitiza) CIC and OIC: 24 mcg
channel twice daily
activator IBS-­C in women ≥18
y: 8 mcg twice daily
Stimulant Glycerin suppository 1 daily
Bisacodyl (Dulcolax) 10 mg suppository
Senna (Senokot, Perdiem) or 5–10 mg PO 3
Senna/docusate (Peri-­Colace) times a week
2–4 tabs twice daily
Enemas Mineral oil retention enema 199–250 mL daily PR
Tap water enema 500–1000 mL PR
Sodium phosphate enema 1 unit PR
(Fleet)
Opioid Methylnaltrexone (Relistor) 8–12 mg 1 dose SC
antagonist every other day as
needed for OIC
with advanced
illness.
450 mg PO once daily
or 12 mg SC once
daily for OIC with
chronic noncancer
pain.
Opioid Naloxegol (Movantik) 12.5–25 mg PO daily
antagonist
1Not US Food and Drug Administration (FDA) approved for this indication.
MECHANISM OF
ACTION TIME TO ONSET (H) ADVERSE EFFECT
Osmotic effect Cannot be calculated Diarrhea
increasing Abdominal pain,
intraluminal fluids, diarrhea
increase transit time
Increase intestinal Unknown Headache, nausea,
fluid secretion and diarrhea
improve fecal transit
Local rectal 8–12 Degeneration of
stimulation, Meissner and
secretory and Auerbach plexus
prokinetic effect
Evacuation induced by 6–8 for a mineral oil Mechanical trauma,
distended colon and enema incontinence, rectal
mechanical lavage 5–15 min for all damage
other enemas
Opioid mu receptor 4 Diarrhea, intestinal
antagonist in gut perforation
decreasing transit
time
Same as Relistor 6–36 Abdominal pain,
opioid withdrawal
reported

Cough
CIC, Chronic idiopathic constipation; IBS-­C, irritable bowel syndrome with constipation; OIC, opioid-­induced constipation; PEG-ES, polyethylene glycol and electrolyte
solution; PO, by mouth; PR, per rectum; SC, subcutaneously.

7
References COUGH
Arshad A, Powell C: Easily missed? Hirschsprung’s disease, Br Med J 345:e5521,
2012. Method of
Barish DF, Crozier RA, Griffin PH: Long-­term treatment with plecanatide was safe Emily Manlove, MD
and tolerable in patients with irritable bowel syndrome with constipation, Curr
Med Res Opin 1–5, 2018.
Bharucha AE, Pemberton JH, Locke GR: American Gastroenterological Association
technical review on constipation, Gastroenterology 144:218–238, 2013.
Gallagher PF, O’Mahony D, Quigley EM: Management of chronic constipation in
the elderly, Drugs Aging 25:807–821, 2008. CURRENT DIAGNOSIS
Gastroenterology: Rome criteria. Available at http://www.romecriteria.org/.
Higgins PD, Johanson JF: Epidemiology of constipation in North America: a system-
atic review, Am J Gastroenterol 99:750–759, 2004. • A
 cute Cough
Larkin PJ, Sykes NP, Centeno C, et al: The management of constipation in palliative • Noninfectious
care: Clinical practice recommendations, Palliat Med 22:796–807, 2008. • Chronic obstructive pulmonary disease exacerbation
McCallum IJ, Ong S, Mercer-­Jones M: Chronic constipation in adults, Br Med J
• Asthma exacerbation
338:b831, 2009.
Nee J, et al: Efficacy of treatments for opioid-­induced constipation: a systemic re- • Congestive heart failure exacerbation
view and meta-­analysis, Clin Gastroenterol Hepatol, 2018 Jan 25. • Pulmonary embolism
Schoenfeld P, et al: Low-­Dose linaclotide (72ug) for chronic idiopathic constipation: • Infectious
A 12-­week, randomized, double-­blind, placebo-­controlled trial, Am J Gastroen-
• Viral rhinosinusitis (the common cold)
terol, 2018, 113-105–114. https://doi.org/10.1038/ajg.2017.230.
Thomas J, Karver S, Cooney GA, et al: Methylnaltrexone for opioid-­induced consti- • Acute bacterial sinusitis
pation in advanced illness, N Engl J Med 358:2332–2343, 2008. • Acute bronchitis (chest cold)
Wald A: Management and prevention of fecal impaction, Curr Gastroenterol Rep • Pneumonia
10:299–501, 2008.
• Pertussis (whooping cough)
Wald A: Constipation: Advances in diagnosis and treatment, JAMA 315(2):185–
191, 2016 Jan 12. • Bronchiolitis (infants)

• C
 hronic cough
• First, evaluate/rule out
• Tobacco smoking and risk for lung cancer
• Angiotensin-­converting enzyme (ACE) inhibitor associ-
ated cough
• Next, evaluate for the three most common etiologies
• Chronic upper airway cough syndrome
• Cough variant asthma/nonasthmatic eosinophilic bron-
chitis
• Gastroesophageal reflux disease
• Last, consider other causes and more advanced testing
(bronchoscopy, high-­resolution computed tomography [CT]
scanning, referral) and consider earlier if history, physical,
or chest x-­ray suggests an alternative diagnosis
• Oral pharyngeal dysphagia
• Lung tumors
• Interstitial pulmonary diseases
• Bronchiectasis
• Occupational and environmental exposures
• Sarcoidosis
• Tuberculosis
• Somatic cough syndrome
• Tic cough
I Symptomatic Care Pending Diagnosis
CURRENT THERAPY
• A cute cough due to viral rhinosinusitis
• Dextromethorphan (Delsym) 30 mg PO every 6 to 8 hours ×
1 week
• Diphenhydramine (Benadryl) 25 mg PO every 4 hours × 1
week
• Nasal saline irrigation twice daily × 1 week
• Acute or subacute cough caused by Bordetella pertussis
• Azithromycin (Z-­Pak)1 500 mg PO on day 1 followed by
250 mg PO daily on days 2 to 5
• Treatment of unexplained chronic cough
• Multimodality speech pathology therapy
8 • Gabapentin (Neurontin) 300 mg PO daily, can be titrated up
to a maximum daily dose of 1800 mg a day in two divided
doses (off label use)
1Not
FDA approved for this indication.
Acute Cough
Acute cough is a cough that lasts fewer than 3 weeks. It is a com-
mon presenting complaint in the primary care physician’s office
and also in the emergency room. The key goal is to differentiate
between those patients whose cough has a benign cause and those
who may be at risk for more serious illness. Infectious causes of
cough are most common, but noninfectious causes should also be
considered. Exacerbations of preexisting pulmonary conditions
such as asthma and chronic obstructive pulmonary disease (COPD)
can be associated with cough, therefore a thorough medical history
should be obtained. Cough can also be associated with decompen-
sated heart failure; in fact, cough is present in 70% of congestive
heart failure (CHF) exacerbations. Also, 30% to 40% of patients
with acute pulmonary embolism (PE) have a new cough at presen-
tation of symptoms, and the classic signs and symptoms of chest
pain, dyspnea, and hypoxia may not always accompany the cough.
Upper respiratory tract infections are a common cause of
benign acute cough. The common cold, also known as viral rhi-
nosinusitis, is probably the most common cause of acute cough.
The lung exam is normal. If fever is present it is low grade and is
only present on the first or second day of illness. Most symptoms
begin to resolve by 7 to 10 days, but cigarette smokers may be
ill for twice as long. Symptomatic treatment is the mainstay of
therapy. First-­generation antihistamines combined with a decon-
gestant and naproxen have been proven to reduce the length of
cough. Second-­generation antihistamines are not effective in the
treatment of cough associated with viral rhinosinusitis; it is likely
that first-­generation antihistamines are effective because of their
anticholinergic properties. Other treatments that may be helpful
include nasal saline irrigation, nasal glucocorticoids, and nasal
decongestants. It is necessary to distinguish viral rhinosinusitis
from acute bacterial rhinosinusitis, which may also be associated
with cough. Less than 2% of all rhinosinusitis has a bacterial
cause. Acute bacterial rhinosinusitis should not be diagnosed
in the first week of symptoms unless the patient displays severe
symptoms such as high fever. Sinus imaging studies are unlikely
to be helpful, as both viral and bacterial sinusitis will have radio-
logic evidence of inflammation.
It is also necessary to distinguish an acute cough caused by an
upper respiratory tract infection and that caused by a lower respi-
ratory tract infection. Furthermore, it is necessary to distinguish
between acute bronchitis, which almost always has a viral cause,
versus pneumonia, which has a bacterial cause. Both illnesses
often have a presenting symptom of cough, which may be pro-
ductive. If there is any derangement in vital signs or evidence of
pulmonary consolidation on the lung exam, a chest x-­ray should
be performed. Infectious Diseases Society of America (IDSA)
guidelines require the presence of consolidation on chest x-­ray
to diagnose pneumonia. Influenza should also be considered for
those patients who have fever and cough during flu season. An
elevated procalcitonin level may help guide the physician in his
or her decision to prescribe antibiotics. Beta agonists should not
be routinely used to alleviate cough in acute viral bronchitis, but
may be helpful for the alleviation of wheezing and are more likely
to benefit patients with airflow obstruction at baseline.
In pediatric patients, bronchiolitis should be considered as a
cause of cough and fever. It is the most common cause of hospi-
talization in those less than 1 year old. The most recent guidelines
recommend abstaining from lab testing (including viral swabs),
radiographic imaging, and treatment with beta agonists, epineph-
rine, or glucocorticoids as these interventions do not change the
course of illness. Exclusive breastfeeding for the first 6 months of
infancy can decrease the morbidity of respiratory infections. Bor-
detella pertussis can cause severe illness with cough and apnea in
infants. However, adults have subtle symptoms and lack the clas-
sic “whooping cough” and posttussive emesis seen in children.
The physician should have suspicion for pertussis in patients
who have a cough lasting longer than 2 weeks and paroxysms of
coughing; the cough can last up to 2 months. The diagnosis can
be confirmed with polymerase chain reaction (PCR). Antibiotics
do not alter the course of illness but reduce the spread of infec-
tion; azithromycin (Zithromax)1 should be given for 3 to 5 days.
Vaccination rates remain low. Pregnant women should be vacci-
nated with each pregnancy and other adults should replace 1 dose
of Td at the earliest convenience.
Chronic Cough
A chronic cough is a cough lasting more than 8 weeks. Patients may
have a presenting symptom of a cough that has been present for
more than 3 but fewer than 8 weeks; this is considered a subacute
cough. In this case, the physician should illicit a history of respira-
tory infection; the patient is likely suffering from a postinfectious
cough, which is related to inflammation of the airway epithelium,
mucus hypersecretion, and/or increased cough reflex sensitivity.
Inhaled corticosteroids may provide some benefit. If there is no
history of recent infection, then the cough should be managed as
a chronic cough. Chest x-­ray can be considered during this time
frame, but if no red flags are present (fever, unintended weight loss,
night sweats, dysphagia, odynophagia, hemoptysis) the physician
and patient together can decide to wait on radiography.
Chronic cough must be approached in a systematic manner,
which is more likely to identify the causative agent of the cough
1Not FDA approved for this indication.
and provide alleviation of symptoms. All of the common causes
of chronic cough (see later) must be considered, as the associated
symptoms and the patient’s description of the cough do not alter
the diagnostic algorithm. It is important to confirm compliance
throughout the treatment course and identify barriers to compli-
ance with the patient. Failure to respond to empiric treatment
does not necessarily rule out a diagnosis, as the patient may have
two diagnoses. Therefore, it is prudent to continue any partially
effective treatment for chronic cough.
First, it must be determined if the patient smokes. If so, the
differential diagnosis is altered. The physician must determine if
the cough is a simple smoker’s cough, chronic bronchitis, or pos-
sibly lung cancer; cough is the most common presenting symptom
of lung cancer. Smokers are less likely to seek help for a cough
and may not see a physician until a more serious problem has
advanced. It is possible for a cough to worsen initially after smok-
ing cessation, but a cough persisting more than 1 month after ces-
sation should be investigated. Any change in a smoker’s cough,
a new cough, and cough with hemoptysis should be investigated.
Physicians should consider low dose CT scanning as screening for
lung cancer in qualifying smokers. The second factor to rule out
in all chronic cough cases is cough induced by an angiotensin-­
converting enzyme (ACE) inhibitor. All patients with chronic
cough should stop taking an ACE inhibitor. The medication is
more likely to cause a cough if it was started in the prior year,
and the cough should resolve within 1 month after cessation of
the ACE inhibitor. The next step to determining the cause of a
chronic cough is to rule out the three most common causes of
cough. Last, all patients with a cough lasting more than 8 weeks
should be evaluated with chest radiography to identify any obvi-
ous causative factors.
Upper Airway Cough Syndrome
Upper airway cough syndrome (UACS), previously called post-
nasal drip syndrome, is likely caused by activation of cough
receptors in the hypopharynx or larynx and increased sensitiv-
ity of these receptors. It is likely the most common cause of
chronic cough. UACS is almost always associated with rhino-
sinusitis, which can be caused by a number of factors (allergic
rhinitis, postinfectious rhinitis, perennial nonallergic rhinitis,
rhinitis resulting from chemical irritants, rhinitis medicamen-
tosa, pregnancy-­associated rhinitis, bacterial sinusitis, allergic
fungal sinusitis, etc.). The patient may complain of frequently
needing to clear the throat or a sensation of “dripping” in the
back of the throat; however, absence of these symptoms does
not rule out UACS, nor does a history of wheezing. Physi-
cal exam may reveal mucus in the posterior oropharynx and
cobblestoning of the mucosa. If the cause of rhinitis is obvi-
ous, it should be specifically treated. Otherwise, a trial of a
first-­generation antihistamine should be started; improvement
should be seen in 2 weeks. If the side effects of this therapy
are intolerable, a nasal antihistamine, nasal anticholinergic, or
nasal corticosteroid can be used. If the diagnosis of UACS is
highly suspected but the patient does not respond to empiric
therapy, sinus CT imaging may be necessary to guide diagnosis
and treatment.
Cough Variant Asthma and Nonasthmatic Eosinophilic
Bronchitis
Cough variant asthma and nonasthmatic eosinophilic bronchitis
(NAEB) both primarily present with a cough, and the patient may
have few other symptoms. Patients with cough variant asthma
will have abnormal spirometry, whereas those with NAEB will
not. When spirometry is performed, bronchoprovocation test-
ing with methacholine should be performed as it increases the
negative predicative value of the test. If spirometry is negative, the
sputum should be evaluated for eosinophils, which are present
in both diseases. Both diseases are treated as asthma; an inhaled
corticosteroid should be started and leukotriene receptor antago-
nists can be considered. A positive response should be expected
within 2 weeks.
Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD) is common, but not
all patients with GERD have an associated cough; therefore, the
presence of GERD does not ensure that it is the source of the
patient’s cough. However, those patients whose cough is clearly
not caused by UACS, cough variant asthma, or NAEB are very
likely to have a GERD-­induced cough. Cough can be caused by
acidic and nonacidic reflux, so a proton pump inhibitor (PPI) may
not always be of benefit. A pH probe can be performed in cases
when it is unclear whether reflux is occurring. All patients should
utilize lifestyle changes to attenuate reflux, such as smoking ces-
sation, avoidance of alcohol and acidic foods, weight loss, and
treatment of sleep apnea. It may take 3 to 6 months of treatment
to see improvement in cough. If the patient does not improve and
GERD is highly suspected, referral to a surgeon may be necessary
for fundoplication.
Other Causes of Chronic Cough
In those patients who still suffer from chronic cough and the
above causes have been ruled out, further investigation should be
sought. Referral to a pulmonologist may be necessary, in addition
to high-­ resolution CT scanning and bronchoscopy. Causative
factors may include oral pharyngeal dysphagia, lung tumors,
interstitial pulmonary diseases, bronchiectasis, occupational and
environmental exposures, sarcoidosis, and tuberculosis. Somatic
cough syndrome (previously referred to as psychogenic cough)
and tic cough (previously referred to as habit cough) may be
considered in some patients; hypnosis, suggestion therapy, and/
or counseling may be beneficial. In patients who remain symp-
tomatic, regardless of known or unknown causes, the diagnosis
of “difficult to treat” cough is made. Assessing cough severity
and quality of life with validated tools may be beneficial. Options
Dizziness and Vertigo
do remain for these patients, including speech language pathol-
ogy intervention, empiric gabapentin, and/or referral to a cough
clinic.
References
Benich III JJ, Carek PJ: Evaluation of the patient with chronic cough, Am fam physi-
cian 2011 Oct 15 84(8), 887–92.
Côté A, Russell RJ, Boulet LP, et al: Managing chronic cough due to asthma and
NAEB in adults and adolescents: CHEST guideline and expert panel report.
Chest. 2020 Jan 20.
Irwin RS, French CL, Chang AB, et al: Classification of cough as a symptom in
adults and management algorithms: CHEST guideline and expert panel report, 9
Chest 2018;153(1):196–209.
DIZZINESS AND VERTIGO
Method of
Jennifer Wipperman, MD, MPH
CURRENT DIAGNOSIS
• B enign paroxysmal positional vertigo
• Repeated, brief episodes lasting less than 1 minute
• Triggered by changes in head position
• Positive Dix-­Hallpike or Supine Roll Test
• Vestibular neuritis
• Single, severe, constant episode lasting days
• Subacute onset
• Positive head impulse test
• Nystagmus is unidirectional and horizontal
• Vestibular migraine
• Recurrent episodes lasting hours to days
• Includes features of migraine headache
• Responds to traditional migraine treatment
and provide alleviation of symptoms. All of the common causes
of chronic cough (see later) must be considered, as the associated
symptoms and the patient’s description of the cough do not alter
the diagnostic algorithm. It is important to confirm compliance
throughout the treatment course and identify barriers to compli-
ance with the patient. Failure to respond to empiric treatment
does not necessarily rule out a diagnosis, as the patient may have
two diagnoses. Therefore, it is prudent to continue any partially
effective treatment for chronic cough.
First, it must be determined if the patient smokes. If so, the
differential diagnosis is altered. The physician must determine if
the cough is a simple smoker’s cough, chronic bronchitis, or pos-
sibly lung cancer; cough is the most common presenting symptom
of lung cancer. Smokers are less likely to seek help for a cough
and may not see a physician until a more serious problem has
advanced. It is possible for a cough to worsen initially after smok-
ing cessation, but a cough persisting more than 1 month after ces-
sation should be investigated. Any change in a smoker’s cough,
a new cough, and cough with hemoptysis should be investigated.
Physicians should consider low dose CT scanning as screening for
lung cancer in qualifying smokers. The second factor to rule out
in all chronic cough cases is cough induced by an angiotensin-­
converting enzyme (ACE) inhibitor. All patients with chronic
cough should stop taking an ACE inhibitor. The medication is
more likely to cause a cough if it was started in the prior year,
and the cough should resolve within 1 month after cessation of
the ACE inhibitor. The next step to determining the cause of a
chronic cough is to rule out the three most common causes of
cough. Last, all patients with a cough lasting more than 8 weeks
should be evaluated with chest radiography to identify any obvi-
ous causative factors.
Upper Airway Cough Syndrome
Upper airway cough syndrome (UACS), previously called post-
nasal drip syndrome, is likely caused by activation of cough
receptors in the hypopharynx or larynx and increased sensitiv-
ity of these receptors. It is likely the most common cause of
chronic cough. UACS is almost always associated with rhino-
sinusitis, which can be caused by a number of factors (allergic
rhinitis, postinfectious rhinitis, perennial nonallergic rhinitis,
rhinitis resulting from chemical irritants, rhinitis medicamen-
tosa, pregnancy-­associated rhinitis, bacterial sinusitis, allergic
fungal sinusitis, etc.). The patient may complain of frequently
needing to clear the throat or a sensation of “dripping” in the
back of the throat; however, absence of these symptoms does
not rule out UACS, nor does a history of wheezing. Physi-
cal exam may reveal mucus in the posterior oropharynx and
cobblestoning of the mucosa. If the cause of rhinitis is obvi-
ous, it should be specifically treated. Otherwise, a trial of a
first-­generation antihistamine should be started; improvement
should be seen in 2 weeks. If the side effects of this therapy
are intolerable, a nasal antihistamine, nasal anticholinergic, or
nasal corticosteroid can be used. If the diagnosis of UACS is
highly suspected but the patient does not respond to empiric
therapy, sinus CT imaging may be necessary to guide diagnosis
and treatment.
Cough Variant Asthma and Nonasthmatic Eosinophilic
Bronchitis
Cough variant asthma and nonasthmatic eosinophilic bronchitis
(NAEB) both primarily present with a cough, and the patient may
have few other symptoms. Patients with cough variant asthma
will have abnormal spirometry, whereas those with NAEB will
not. When spirometry is performed, bronchoprovocation test-
ing with methacholine should be performed as it increases the
negative predicative value of the test. If spirometry is negative, the
sputum should be evaluated for eosinophils, which are present
in both diseases. Both diseases are treated as asthma; an inhaled
corticosteroid should be started and leukotriene receptor antago-
nists can be considered. A positive response should be expected
within 2 weeks.
Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD) is common, but not
all patients with GERD have an associated cough; therefore, the
presence of GERD does not ensure that it is the source of the
patient’s cough. However, those patients whose cough is clearly
not caused by UACS, cough variant asthma, or NAEB are very
likely to have a GERD-­induced cough. Cough can be caused by
acidic and nonacidic reflux, so a proton pump inhibitor (PPI) may
not always be of benefit. A pH probe can be performed in cases
when it is unclear whether reflux is occurring. All patients should
utilize lifestyle changes to attenuate reflux, such as smoking ces-
sation, avoidance of alcohol and acidic foods, weight loss, and
treatment of sleep apnea. It may take 3 to 6 months of treatment
to see improvement in cough. If the patient does not improve and
GERD is highly suspected, referral to a surgeon may be necessary
for fundoplication.
Other Causes of Chronic Cough
In those patients who still suffer from chronic cough and the
above causes have been ruled out, further investigation should be
sought. Referral to a pulmonologist may be necessary, in addition
to high-­ resolution CT scanning and bronchoscopy. Causative
factors may include oral pharyngeal dysphagia, lung tumors,
interstitial pulmonary diseases, bronchiectasis, occupational and
environmental exposures, sarcoidosis, and tuberculosis. Somatic
cough syndrome (previously referred to as psychogenic cough)
and tic cough (previously referred to as habit cough) may be
considered in some patients; hypnosis, suggestion therapy, and/
or counseling may be beneficial. In patients who remain symp-
tomatic, regardless of known or unknown causes, the diagnosis
of “difficult to treat” cough is made. Assessing cough severity
and quality of life with validated tools may be beneficial. Options
Dizziness and Vertigo
do remain for these patients, including speech language pathol-
ogy intervention, empiric gabapentin, and/or referral to a cough
clinic.
References
Benich III JJ, Carek PJ: Evaluation of the patient with chronic cough, Am fam physi-
cian 2011 Oct 15 84(8), 887–92.
Côté A, Russell RJ, Boulet LP, et al: Managing chronic cough due to asthma and
NAEB in adults and adolescents: CHEST guideline and expert panel report.
Chest. 2020 Jan 20.
Irwin RS, French CL, Chang AB, et al: Classification of cough as a symptom in
adults and management algorithms: CHEST guideline and expert panel report, 9
Chest 2018;153(1):196–209.
DIZZINESS AND VERTIGO
Method of
Jennifer Wipperman, MD, MPH
CURRENT DIAGNOSIS
• B enign paroxysmal positional vertigo
• Repeated, brief episodes lasting less than 1 minute
• Triggered by changes in head position
• Positive Dix-­Hallpike or Supine Roll Test
• Vestibular neuritis
• Single, severe, constant episode lasting days
• Subacute onset
• Positive head impulse test
• Nystagmus is unidirectional and horizontal
• Vestibular migraine
• Recurrent episodes lasting hours to days
• Includes features of migraine headache
• Responds to traditional migraine treatment

• M énière’s disease
• Recurrent episodes of vertigo lasting hours
• May have hearing loss, tinnitus, or ear fullness
• Red flags for stroke include:
• Sudden onset
• Risk factors for stroke
• Bidirectional or purely vertical nystagmus
• Abnormal HINTS exam
• Focal neurologic signs
• Inability to walk
CURRENT THERAPY
• B enign paroxysmal positional vertigo
• The canalith repositioning procedure (Epley maneuver) is
the most effective treatment.
• Avoid vestibular suppressant medications
• Observation with close follow-­up is optional if a patient
will not tolerate the canalith repositioning procedure and
I Symptomatic Care Pending Diagnosis
if symptoms are mild
• Vestibular neuritis
• Brief symptomatic care with benzodiazepines, antiemetics,
and antihistamines
• Early vestibular rehabilitation speeds recovery.
• Use of corticosteroids is controversial.
The “dizzy” patient is often a frustrating phenomenon in clinical
medicine. However, after a careful history and physical examina-
tion, most patients can be diagnosed and serious causes excluded.
Peripheral causes of vertigo are usually benign and include ves-
tibular neuritis and benign paroxysmal positional vertigo (BPPV).
Life-­threatening central causes include stroke, demyelinating dis-
ease, and an intracranial mass. The first step in evaluating vertigo
is differentiating among the four types of dizziness: near syncope
or light-­headedness, disequilibrium, psychogenic dizziness, and
10 true vertigo. True vertigo is a false sense of motion, and patients
often report that “the room is spinning.” This chapter will focus
on the two most common causes of episodic vertigo: BPPV and
vestibular neuritis.
Epidemiology
Vertigo is a common office complaint. Every year, millions of
Americans are evaluated for dizziness in ambulatory care settings,
and approximately 50% of these cases are vertigo. BPPV and ves-
tibular neuritis are two of the most common causes of vertigo
seen in the office setting.
Risk Factors
BPPV is seven times more likely in individuals over age 60, and it
is also more common in women. A history of prior head trauma
and other vestibular disorders increases risk of BPPV. There are
no identified risk factors for vestibular neuritis.
Pathophysiology
BPPV is thought to occur when calcium carbonate debris (oto-
conia) are dislodged and float freely in the semicircular canals
of the inner ear. The posterior canal is most often involved.
During head movement, loose otoconia move in the canal and
cause a continued sense of motion for a few seconds until they
settle. The pathophysiology of vestibular neuritis is uncertain.
Limited evidence supports a viral infection, most likely HSV-­1,
which causes inflammation of the eighth cranial nerve. When
hearing loss accompanies vertigo, the condition is called acute
labrynthitis.
Clinical Manifestations
The history and physical examination are fundamental in the eval-
uation of vertigo. Key questions include the frequency and dura-
tion of attacks, triggers such as positional or pressure changes,
prior head trauma, associated neurologic symptoms, hearing
loss, and headache. A personal history of diabetes, hypertension,
and hyperlipidemia are risk factors for stroke. BPPV, stroke, and
migraine can have a familial preponderance. Many medications,
including anticonvulsants and antihypertensives, cause dizziness.
BPPV causes brief, recurrent episodes that last less than 1 min-
ute and are brought on by changes in head movement or position.
Nausea and vomiting may be associated. Vestibular neuritis usu-
ally has a subacute onset over several hours, peaks in intensity for
1 to 2 days, and then gradually subsides over the next few weeks.
Symptoms of vertigo are constant, and nausea and vomiting can
be severe during the first few days. Patients with vestibular neuri-
tis may have difficulty standing and veer toward the affected side.
Although changes in position worsen the vertigo in vestibular
neuritis, vertigo is always present at baseline. In BPPV, patients
have no vertigo between attacks.
General physical examination should include a thorough car-
diovascular, ear, nose, throat, and neurologic examination. The
neurologic examination can differentiate between benign (periph-
eral) and life-­threatening (central) causes based on the ability to
walk, type of nystagmus, results of the head impulse test, and
presence of associated neurologic signs (Table 1).
Patients with vestibular neuritis may have difficulty walking,
but the inability to walk is a red flag for a central lesion. Nys-
tagmus is unidirectional (always beats in the same direction) and
horizontal in vestibular neuritis, and is suppressed by visual fixa-
tion. Having a patient focus on an object in the room will stop
the nystagmus, which reappears if a blank sheet of paper is placed
a few inches in front of the patient’s face. Nystagmus in central
causes is not suppressed by visual fixation and may be direction-­
changing (nystagmus beats to the right when the patient looks
right, and beats to the left when the patient looks left) or purely
vertical. The head impulse test (Figure 1) is positive in peripheral
causes like vestibular neuritis. The examiner holds the patient’s
head while the patient fixes her eyes on the examiner’s nose, and
then the examiner quickly moves the patient’s head 10 degrees
to the right and left. If a saccade (the eyes look away and then
re-­fixate on the examiner’s nose) is found, this indicates a periph-
eral lesion on the side that the head is turned toward. Central
lesions will not cause saccades, and the head impulse test will be
negative. HINTS (Head Impulse test, Nystagmus, Test of Skew),
which combines three physical examination findings, has been
found to have a 97% sensitivity and 99% specificity for a cen-
tral cause of vertigo in the acute setting and to be more accurate
than MRI in the initial 24 hours after symptom onset. If one or
more of the tests indicate a central cause, (e.g., a negative head
impulse test, direction-­changing horizontal nystagmus, or vertical
eye misalignment grossly observed or detected on cover-­uncover
test), then the HINTS test is considered positive for a central
cause and imaging should be obtained. A negative HINTS exam
is an excellent rule-­out test for stroke, with a negative likelihood
ratio of 0.02.
The Dix-­Hallpike maneuver is diagnostic of posterior canal
BPPV (Figure 2). The patient should be warned that nausea
and vomiting may occur. After the patient is placed in the head-­
hanging position, there is a 5-­to 20-­second latency period before
the nystagmus and symptoms appear. Both the nystagmus and
vertigo will increase in severity and then resolve within 60 sec-
onds. The nystagmus observed is up-­beating and torsional. If
nystagmus is constant for as long as the head is in the hanging
position, the patient should be evaluated for a central cause. The
maneuver should be repeated with the head held to the opposite
side. The side that elicits the symptoms and nystagmus diagno-
ses BPPV in the ipsilateral ear. If both sides elicit symptoms, the
patient may have bilateral BPPV. If the test is negative and BPPV
is strongly suspected, the patient should lie supine and the exam-
iner can turn the head to each side (supine roll test; Figure 3).
 TABLE 1  Differentiating Peripheral and Central Causes of Vertigo
PERIPHERAL CAUSES
BPPV VESTIBULAR NEURITIS CENTRAL CAUSES
History Brief, recurrent attacks of vertigo Subacute onset Sudden onset
lasting less than 1 minute Constant and severe vertigo lasting Risk factors for stroke
Triggered by positional changes days May have severe headache
No vertigo between attacks Nausea and vomiting may be
severe
Nystagmus Up-­beating and torsional Horizontal and unidirectional Bidirectional
Pure vertical
Pure torsional
Gait Unaffected between episodes May veer towards affected side Unable to walk
Specialized physical examination Positive Dix-­Hallpike or Positive head impulse test HINTS exam abnormal
tests Positive supine roll test Visual fixation stops nystagmus Visual fixation does not stop
nystagmus
Additional neurologic signs Rare Rare Common (e.g., dysarthria,
aphasia, incoordination,
weakness, or numbness)

Abbreviation: BPPV = benign paroxysmal positional vertigo.

Dizziness and Vertigo

PSC
E D C B
UT E
A

C 11
D

Figure 1 Head impulse test. Top panel shows a positive head impulse
test. The examiner moves the patient’s head quickly 10 degrees to the
side, in this case to the patient’s left. A catch-­up saccade is observed when
the patient looks away and then refixes on the visual target, indicating
a peripheral lesion on the left. Lower figure shows a normal head im-
pulse test. The patient maintains visual fixation during head movement.
Adapted from Seemungal BM, Bronstein AM. A practical approach to
acute vertigo. Pract Neurol 2008; 8:211–21.
This maneuver will cause vertigo and nystagmus in patients with
horizontal canal BPPV.
Diagnosis
BPPV and vestibular neuritis are diagnosed clinically. Further
diagnostic testing is indicated if the diagnosis is uncertain or a cen-
tral cause is suspected. Audiometry may be abnormal in Ménière’s
disease. MRI is the best imaging test for central lesions because it
includes the posterior fossa and is most sensitive for stroke. Ves-
tibular function testing is useful if the diagnosis is unclear or in
cases of refractory vertigo. Vestibular function testing evaluates
the ocular and vestibular response to position changes and caloric
stimulation. Video-­ oculographic recordings of nystagmus can
magnify the eye and allow for repeated viewings for further study.
Some patients with BPPV may have additional vestibular disorders
causing vertigo that vestibular function testing can elucidate.
Figure 2 Treatment maneuver for posterior canal benign paroxysmal po-
sitional vertigo affecting the right ear. To treat the left ear, the procedure
is reversed. The drawing of the labyrinth in the center shows the position
of the particle as it moves around the posterior semicircular canal (PSC)
and into the utricle (UT). The patient is seated upright, with head fac-
ing the examiner, who is standing on the right. A, The patient is rapidly
moved to head-­hanging right position (Dix-­Hallpike test). This position
is maintained until the nystagmus ceases. B, The examiner moves to the
head of the table, repositioning hands as shown. C, The head is rotated
quickly to the left with right ear upward. This position is maintained for
30 seconds. D, The patient rolls onto the left side while the examiner rap-
idly rotates the head leftward until the nose is directed toward the floor.
This position is then held for 30 seconds. E, The patient is rapidly lifted
into the sitting position, now facing left. The entire sequence should be re-
peated until no nystagmus can be elicited. After the maneuver, the patient
is instructed to avoid head-­hanging positions to prevent the particles from
reentering the posterior canal. Reprinted with permission from Rakel RE.
Conn’s Current Therapy 1995. Philadelphia, WB Saunders, 1995, p 839.
Differential Diagnosis
Ménière’s disease is suspected in patients with the triad of tinni-
tus, fluctuating hearing loss, and vertigo. Episodes usually last
hours, are disabling, and are recurrent over years, over time
leading to permanent dysfunction. Migrainous vertigo features
episodes lasting hours to days in patients with other migraine
symptoms such as headache, photophobia, phonophobia, or
 1

2 3
I Symptomatic Care Pending Diagnosis

Figure 3 Supine roll test. Patient begins lying supine facing upward. The patient’s head is rotated to one side laterally 90 degrees and the examiner
observes for nystagmus and vertigo. Once symptoms resolve, the patient’s head is rotated back to midline. Next, the patient’s head is rotated 90 degrees
laterally to the opposite side and the examiner observes for nystagmus and vertigo. The side with the worst symptoms indicates the involved ear. (From
Kerber KA, et al: Benign paroxysmal positional vertigo in the acute care setting. NCL, Elsevier, 2015.)

aura. Central lesions such as stroke or intracranial mass are
most concerning. Red flags for stroke include sudden onset,
risk factors for stroke, associated neurologic signs, inability
to walk, abnormal HINTS exam, severe associated headache,
and characteristic nystagmus. Posttraumatic vertigo may occur
in patients after head trauma who present with vertigo, tinni-
tus, and headache. A perilymphatic fistula is rare, but may be
suspected in a patient with episodic vertigo after head trauma,
heavy lifting, or barotrauma. Pressure changes with sneez-
12 ing or coughing trigger vertigo attacks. Postural hypotension
should be ruled out in all patients. An acoustic neuroma pres-
ents with slowly progressive, unilateral sensorineural hearing
loss and tinnitus. Many patients may have an unsteady gait,
but true vertigo is rare.
Treatment
Posterior canal BPPV is best treated with the canalith reposition-
ing procedure (CRP), such as the Epley maneuver (Figure 2).
Studies have shown the procedure is safe and effective with an
odds ratio of 4.2 (95% CI. 2.3-­11.4) for symptom resolution.
Patients should be warned that nausea or vomiting may occur
during the procedure, and may be pretreated with an antiemetic
medication. The procedure can be repeated immediately if unsuc-
cessful, and the majority of patients will respond after three
attempts. Posttreatment activity restrictions are unnecessary.
Horizontal canal BPPV can be treated with the barbeque roll
maneuver (Figure 4). Vestibular rehabilitation (VR) is a treatment
option for BPPV but is significantly less effective than the canalith
repositioning procedure. VR is helpful in patients with chronic,
nonspecific dizziness after successful treatment with CRP and for
improving gait stability in those with increased fall risk, such as
the elderly. Observation is an option if symptoms are mild and if
a patient will not tolerate the canalith repositioning procedure.
However, time to resolution with observation is 1–3 months, and
recurrence rates are higher compared to treatment with CRP.
Vestibular-­suppressant medications such as antihistamines and
benzodiazepines are discouraged because they increase fall risk
and treatment with CRP is effective. Surgery is rarely needed for
BPPV, but may be helpful in refractory cases.
Vestibular neuritis is primarily treated with rest, vestibular sup-
pressant medications, and vestibular rehabilitation. Patients may
initially be hospitalized if symptoms, such as nausea and vomiting,
are severe or if stroke is suspected. Treatment with antihistamines
(dimenhydrinate [Dramamine]1 50 mg every 6 hours), antiemetics
(promethazine [Phenergan]1 25 mg every 6 hours), or benzodiaz-
epines (lorazepam [Ativan]1 1 to 2 mg every 4 hours) may be used
to treat severe symptoms. However, these should not be continued
for more than 2 to 3 days because they inhibit central compensa-
tion. In vestibular neuritis, patients’ vertigo improves not due to
return of vestibular nerve function, but due to central compensa-
tion for the peripheral deficit. Using vestibular suppressants blocks
central compensation and lengthens the course of the disease. The
use of corticosteroids is controversial; a 2011 Cochrane review
concluded that there is insufficient evidence to recommend corti-
costeroids for the treatment of vestibular neuritis. Finally, antiviral
medications have not been proven effective for vestibular neuritis.
For patients with vestibular neuritis, vestibular rehabilitation
should be started as soon as symptoms improve and a patient can
tolerate the exercises. Exercises include balance and gait training
as well as coordination of head and eye movements. Vestibular
rehabilitation hastens recovery and improves balance, gait, and
vision by increasing central compensation for vestibular dysfunc-
tion. Exercises may be home-­based for compliant patients with
mild symptoms, whereas formal referral may be more beneficial
for patients with severe symptoms, or for the elderly.
Monitoring
Patients diagnosed with BPPV should be reassessed in 1 month
regardless of treatment. Failure to improve warrants further eval-
uation for other etiologies, including central causes. Similarly,
patients with vestibular neuritis should slowly improve over sev-
eral weeks, and failure to do so suggests alternative diagnoses.
1Not FDA approved for this indication.
 A B

C D

Dizziness and Vertigo

13

E
Figure 4 Barbecue roll (Lempert maneuver). Patient begins lying supine facing upward (A). Head is rotated laterally 90 degrees toward the affected
ear (B). Next, the head is rotated another 90 degrees laterally back to midline (B). Next, the head is rotated laterally 90 degrees toward the opposite side
(C). Next, the head is rotated laterally 90 degrees in the same direction (D). Finally, with the patient’s head in the same position, the patient is brought
into a seated position (E). Each position is held 30 to 60 seconds, long enough for symptoms to occur and then resolve. Once resolved, the patient is
moved into the next position. (From Moseley L, Cueco RT: Essential guide to the cervical spine -­Volume 2: Clinical Syndromes and Manipulative
Treatment. Elsevier, 2016.)

Complications at increased risk for BPPV and Ménière’s disease. Vestibular

Patients with BPPV are at increased risk for falls. Thirty per-
cent of elderly patients with BPPV have multiple falls in a
year. Thus patients should be assessed for fall risk, functional
mobility, and balance. Home safety evaluation and home
supervision should be considered. BPPV often recurs, with an
estimated rate of 15% per year. Counseling patients about
recurrence can lead to earlier recognition, earlier treatment,
and avoidance of falls. Patients with vestibular neuritis are
neuritis rarely recurs.
References
Baloh RW: Vestibular neuritis, N Engl J Med 348:1027–1032, 2003.
Bhattacharyya N, Gubbels SP, Schwartz SR, et al: Clinical practice guideline: benign
paroxysmal positional vertigo (update), Otolaryngol Head Neck Surg. 156(3_
suppl):S1–S47, 2017.
Chan Y: Differential diagnosis of dizziness, Otolaryngol Head Neck Surg 17:200–
203, 2009.
 Epley JM: The canalith repositioning procedure: for treatment of benign paroxysmal
positional vertigo, Otolaryngol Head Neck Surg 107:399–404, 1992.
Fishman JM, Burgess C, Waddell A: Corticosteroids for the treatment of idiopathic
acute vestibular dysfunction (vestibular neuritis), Cochran Database Syst Rev 5,
2011, CD008607. Review.
Hilton MP, Pinder DK: The Epley (canalith repositioning) manoeuvre for benign par-
oxysmal positional vertigo, Cochrane Database Syst Rev. 12, 2014, CD003162.
Kerber KA: Vertigo and dizziness in the emergency department, Emerg Med Clin
North Am 27:39–50, 2009.
McDonnell MN, Hillier SL: Vestibular rehabilitation for unilateral peripheral ves-
tibular dysfunction, Cochrane Database Syst Rev. 1, 2015, CD005397.
Newman-­Toker DE, Kerber KA, Hsieh YH, et al: HINTS outperforms ABCD2 to
screen for stroke in acute continuous vertigo and dizziness, Acad Emerg Med
20(10):986–996, 2013.
Seemungal BM, Bronstein AM: A practical approach to acute vertigo, Pract Neurol
8:211–221, 2008.
FATIGUE
Method of
Janet C. Lindemann, MD, MBA
CURRENT DIAGNOSIS
I Symptomatic Care Pending Diagnosis
• T he clinical evaluation of fatigue begins with a thorough
medical and psychosocial history.
• Consider monitoring for a month before beginning a labora-
tory evaluation, because it usually does not yield a diagnosis.
Initial evaluation should include a complete blood count
(CBC), electrolytes, glucose, liver and kidney function tests,
thyroid function tests, and urinalysis.
• Among the many possible causes of fatigue, the most com-
mon include depression, environmental stress, anemia, and
diabetes. In many cases, a cause is not determined.
CURRENT THERAPY
• A ny underlying cause discovered in the history, examination,
or laboratory evaluation should be treated.
14 • If depression, anxiety, or environmental stress is suspected,
early assessment and treatment is important.
• Symptom relief includes exercise, regular sleep habits, family
discussion about the impact of fatigue, and a symptom and
sleep diary.
Epidemiology
Fatigue or tiredness is a common complaint in the general popu-
lation, representing the chief complaint in nearly 10% of patients
presenting to a primary care physician and reported as a symp-
tom in 21% of all patient encounters. While acute, prolonged,
and chronic fatigue are relatively common, chronic fatigue syn-
drome is relatively rare.
Risk Factors
Risk factors for fatigue in adolescence include having depressive
symptoms, being highly sedentary, and, conversely, being highly
physically active. In adults, risk factors include age over 65 years,
presence of one or more chronic medical conditions, and female
gender. Precipitating factors include physical stresses such as
infectious mononucleosis and psychological stresses such as job-­
related problems. Perpetuating factors include physical inactivity,
emotional disorders, and disturbances of sleep.
Prevention
Because physical inactivity, psychological stress, and lack of sleep
are predisposing and perpetuating factors for fatigue, it is helpful
to advise patients about stress reduction, regular exercise, and
proper sleep habits.
BOX 1  Common Causes of Fatigue: DEAD TIRED
D Depression T Thyroid, Tumors
E Environment/lifestyle I Infection, Insomnia
A Anxiety, Anemia R Rheumatologic
D Diabetes/endocrine E Endocarditis/cardiovascular
D Drugs (medications or
substance abuse)
Clinical Manifestations
Fatigue is characterized by general malaise, vague physical discom-
fort, and an inability to perform routine activities. Acute fatigue
is short-­lived and generally attributable to physical exertion or an
acute illness. Prolonged fatigue is defined as self-­reported, persis-
tent fatigue lasting 1 month or longer, whereas chronic fatigue is
defined as similar symptoms lasting 6 months or more.
Diagnosis
The clinical evaluation begins with a thorough medical and psy-
chosocial history. It is important to allow the patient to speak
uninterrupted for the first minute or two of the interview, because
this often provides pertinent clues. The history should include
exploration of all medically unexplained symptoms, inquiry into
work and life stressor issues, questions regarding alcohol and
other substance use, and the current use of prescription, over-­the-­
counter, and alternative therapies. A mental status examination
and screening for depression and anxiety should follow. The Beck
Depression Inventory or SIG-­ E-­CAPS mnemonic (Sleep, Inter-
est, Guilt, Energy, Concentration, Appetite, Psychomotor retar-
dation, Suicidal) are useful screening tools. The challenge with
the diagnostic workup for fatigue is that most laboratory tests
do not yield a significant diagnosis. Repeated studies show that
only about 15% of patients in primary care settings will have an
organic cause for their fatigue (Harrison, Ponka), and laboratory
results affect management in as little as 5% of patients (Rosen-
thal). The following recommendations for the laboratory investi-
gation of fatigue are adapted from guidelines developed by Dutch,
Canadian, and Australian general practice groups (Harrison):
• Consider monitoring for a month after initial presentation,
while initiating conservative management.
• CBC, electrolytes, glucose, liver and kidney function tests, thy-
roid function tests, urinalysis.
• Clues from the history and examination may indicate the need
for erythrocyte sedimentation rate, monospot, antinuclear an-
tigen testing, or chest radiography.
Differential Diagnosis
The common causes of fatigue are represented in the mnemonic
DEAD TIRED (Box 1). Depression, environmental factors such
as lifestyle, anxiety, and anemia are among the most common
causes of fatigue. Diabetes and other endocrine disorders, includ-
ing thyroid disease, should be considered, as well as an undis-
covered tumor. Many infections, especially those of viral origin,
cause fatigue, as well as insomnia and sleep disorders such as
obstructive sleep apnea. Rheumatologic disorders, such as rheu-
matoid arthritis, systemic lupus erythematosus, and fibromyalgia,
are often accompanied by fatigue. Endocarditis, while rare, is a
must-­not-­miss diagnosis, as are other cardiac conditions such as
coronary artery disease. Finally, drugs, either prescription or of
personal use or abuse, should be considered.
Chronic fatigue syndrome is a specific clinical diagnosis charac-
terized by unexplained persistent or relapsing fatigue, not relieved
by rest, that substantially limits daily activity. In addition, there
must be at least four of the following: memory or concentration
impairment, sore throat, tender cervical or axillary lymph nodes,
muscle pain, multijoint pain without swelling or tenderness, new
headaches, unrefreshing sleep, or postexertional malaise lasting
more than 24 hours.
 Epley JM: The canalith repositioning procedure: for treatment of benign paroxysmal
positional vertigo, Otolaryngol Head Neck Surg 107:399–404, 1992.
Fishman JM, Burgess C, Waddell A: Corticosteroids for the treatment of idiopathic
acute vestibular dysfunction (vestibular neuritis), Cochran Database Syst Rev 5,
2011, CD008607. Review.
Hilton MP, Pinder DK: The Epley (canalith repositioning) manoeuvre for benign par-
oxysmal positional vertigo, Cochrane Database Syst Rev. 12, 2014, CD003162.
Kerber KA: Vertigo and dizziness in the emergency department, Emerg Med Clin
North Am 27:39–50, 2009.
McDonnell MN, Hillier SL: Vestibular rehabilitation for unilateral peripheral ves-
tibular dysfunction, Cochrane Database Syst Rev. 1, 2015, CD005397.
Newman-­Toker DE, Kerber KA, Hsieh YH, et al: HINTS outperforms ABCD2 to
screen for stroke in acute continuous vertigo and dizziness, Acad Emerg Med
20(10):986–996, 2013.
Seemungal BM, Bronstein AM: A practical approach to acute vertigo, Pract Neurol
8:211–221, 2008.
FATIGUE
Method of
Janet C. Lindemann, MD, MBA
CURRENT DIAGNOSIS
I Symptomatic Care Pending Diagnosis
• T he clinical evaluation of fatigue begins with a thorough
medical and psychosocial history.
• Consider monitoring for a month before beginning a labora-
tory evaluation, because it usually does not yield a diagnosis.
Initial evaluation should include a complete blood count
(CBC), electrolytes, glucose, liver and kidney function tests,
thyroid function tests, and urinalysis.
• Among the many possible causes of fatigue, the most com-
mon include depression, environmental stress, anemia, and
diabetes. In many cases, a cause is not determined.
CURRENT THERAPY
• A ny underlying cause discovered in the history, examination,
or laboratory evaluation should be treated.
14 • If depression, anxiety, or environmental stress is suspected,
early assessment and treatment is important.
• Symptom relief includes exercise, regular sleep habits, family
discussion about the impact of fatigue, and a symptom and
sleep diary.
Epidemiology
Fatigue or tiredness is a common complaint in the general popu-
lation, representing the chief complaint in nearly 10% of patients
presenting to a primary care physician and reported as a symp-
tom in 21% of all patient encounters. While acute, prolonged,
and chronic fatigue are relatively common, chronic fatigue syn-
drome is relatively rare.
Risk Factors
Risk factors for fatigue in adolescence include having depressive
symptoms, being highly sedentary, and, conversely, being highly
physically active. In adults, risk factors include age over 65 years,
presence of one or more chronic medical conditions, and female
gender. Precipitating factors include physical stresses such as
infectious mononucleosis and psychological stresses such as job-­
related problems. Perpetuating factors include physical inactivity,
emotional disorders, and disturbances of sleep.
Prevention
Because physical inactivity, psychological stress, and lack of sleep
are predisposing and perpetuating factors for fatigue, it is helpful
to advise patients about stress reduction, regular exercise, and
proper sleep habits.
BOX 1  Common Causes of Fatigue: DEAD TIRED
D Depression T Thyroid, Tumors
E Environment/lifestyle I Infection, Insomnia
A Anxiety, Anemia R Rheumatologic
D Diabetes/endocrine E Endocarditis/cardiovascular
D Drugs (medications or
substance abuse)
Clinical Manifestations
Fatigue is characterized by general malaise, vague physical discom-
fort, and an inability to perform routine activities. Acute fatigue
is short-­lived and generally attributable to physical exertion or an
acute illness. Prolonged fatigue is defined as self-­reported, persis-
tent fatigue lasting 1 month or longer, whereas chronic fatigue is
defined as similar symptoms lasting 6 months or more.
Diagnosis
The clinical evaluation begins with a thorough medical and psy-
chosocial history. It is important to allow the patient to speak
uninterrupted for the first minute or two of the interview, because
this often provides pertinent clues. The history should include
exploration of all medically unexplained symptoms, inquiry into
work and life stressor issues, questions regarding alcohol and
other substance use, and the current use of prescription, over-­the-­
counter, and alternative therapies. A mental status examination
and screening for depression and anxiety should follow. The Beck
Depression Inventory or SIG-­ E-­CAPS mnemonic (Sleep, Inter-
est, Guilt, Energy, Concentration, Appetite, Psychomotor retar-
dation, Suicidal) are useful screening tools. The challenge with
the diagnostic workup for fatigue is that most laboratory tests
do not yield a significant diagnosis. Repeated studies show that
only about 15% of patients in primary care settings will have an
organic cause for their fatigue (Harrison, Ponka), and laboratory
results affect management in as little as 5% of patients (Rosen-
thal). The following recommendations for the laboratory investi-
gation of fatigue are adapted from guidelines developed by Dutch,
Canadian, and Australian general practice groups (Harrison):
• Consider monitoring for a month after initial presentation,
while initiating conservative management.
• CBC, electrolytes, glucose, liver and kidney function tests, thy-
roid function tests, urinalysis.
• Clues from the history and examination may indicate the need
for erythrocyte sedimentation rate, monospot, antinuclear an-
tigen testing, or chest radiography.
Differential Diagnosis
The common causes of fatigue are represented in the mnemonic
DEAD TIRED (Box 1). Depression, environmental factors such
as lifestyle, anxiety, and anemia are among the most common
causes of fatigue. Diabetes and other endocrine disorders, includ-
ing thyroid disease, should be considered, as well as an undis-
covered tumor. Many infections, especially those of viral origin,
cause fatigue, as well as insomnia and sleep disorders such as
obstructive sleep apnea. Rheumatologic disorders, such as rheu-
matoid arthritis, systemic lupus erythematosus, and fibromyalgia,
are often accompanied by fatigue. Endocarditis, while rare, is a
must-­not-­miss diagnosis, as are other cardiac conditions such as
coronary artery disease. Finally, drugs, either prescription or of
personal use or abuse, should be considered.
Chronic fatigue syndrome is a specific clinical diagnosis charac-
terized by unexplained persistent or relapsing fatigue, not relieved
by rest, that substantially limits daily activity. In addition, there
must be at least four of the following: memory or concentration
impairment, sore throat, tender cervical or axillary lymph nodes,
muscle pain, multijoint pain without swelling or tenderness, new
headaches, unrefreshing sleep, or postexertional malaise lasting
more than 24 hours.
Treatment
The treatment of fatigue begins with acknowledging the
patient’s concern and providing reassurance and information
about the natural course and most frequent causes of fatigue.
Any underlying cause discovered in the history, examination,
or laboratory evaluation should be treated. If depression,
anxiety, or environmental stress is suspected, early assessment
and treatment is important. In fatigue that remains unex-
plained, therapy should emphasize symptom relief and include
exercise, regular sleep habits, family discussion about the
impact of fatigue, and a symptom and sleep diary. These same
therapies, along with cognitive behavioral therapy, have been
shown to have moderate benefit in chronic fatigue syndrome.
Monitoring
Ongoing fatigue can be monitored through a three question
assessment:
• Are you experiencing fatigue?
• If so, how severe has it been, on average, during the past week?
(0–3 is mild fatigue, 4–6 moderate, and 7–10 severe)
• How does fatigue interfere with your ability to function?
References
Beck A, Ward C, Mendelson M, et al: An inventory for measuring depression, Arch
Gen Psychiatry 4:561, 1961.
Gialamas A, Beilby JJ, Pratt NL, et al: Investigating tiredness in Australian general
practice, Aust Fam Physician 32:663, 2003.
Harrison M: Pathology testing in the tired patient: a rational approach, Aust Fam
Physician 37:908, 2008.
Poluri A, Mores J, Cook DB, et al: Fatigue in the elderly population, Phys Med
Rehabil Clin N Am 16:91, 2005.
Ponka D, Kirlew M: Top 10 differential diagnoses in family medicine: Fatigue, Can
Fam Physician 53:892, 2007.
Rosenthal TC, Majeroni BA, Pretorius R, Malik K: Fatigue: An overview, Am Fam
Physician 78:1173, 2008.
Sharpe M, Wilks D: Fatigue, BMJ 325:480, 2002.
Viner RM, Clark C, Taylor SJ, et al: Longitudinal risk factors for persistent fatigue
in adolescents, Arch Pediatr Adolesc Med 162:469, 2008.
FEVER
Method of
Alan R. Roth, DO; and Gina M. Basello, DO
CURRENT DIAGNOSIS
• N umerous endogenous and exogenous factors play a role
in determining body temperature. Current standards define
fever as an oral temperature of ≥100.4 °F (≥38 °C).
• Though temperature varies with measurement technique, in
clinical practice, most recommendations refer to oral, rectal,
and axillary temperature measurements, with rectal tempera-
ture being the standard of care in infants and young children.
• Tympanic thermometers should not be used in young chil-
dren.
• Fever is not an illness. It is the body’s physiologic response to
a disease process and has beneficial effects in fighting infec-
tion.
• All neonates with a fever should be admitted to the hospi-
tal for a full sepsis evaluation. For infants between 1 and 3
months of age, evidence-­based guidelines, along with clinical
evaluation, determine the diagnostic and therapeutic ap-
proach.
• With widespread immunization use, the incidence of bacte-
remia and bacterial meningitis in young infants has signifi-
cantly decreased, and UTI is now the most prevalent bacterial
infection, with the most common etiologic pathogen being E.
coli.
• U rine leukocyte esterase has emerged as a highly accurate
diagnostic test for UTI in febrile infants with greater than
95% sensitivity.
• FUO requires a systematic, thoughtful, and thorough evalua-
tion based on the age of the patient and the existing clinical
evidence, with repeated clinical assessments being essential.
• Hyperthermia is an unregulated, significant elevation of core
body temperature above the normal diurnal range due to
failure of thermoregulation from a hypothalamic insult, not
a pyogenic source, and is considered a medical emergency.
It is not synonymous with fever and often requires immedi-
ate intervention to avoid deleterious central nervous system
(CNS) effects.
CURRENT THERAPY
• T reating a fever significantly increases the patient’s level of
comfort, activity, and oral feeding and fluid intake, in addi-
tion to decreasing the body temperature.
• Multiple randomized, controlled trials reveal that treating fe-
ver does not shorten or prolong the overall duration of illness
or reduce the occurrence of febrile seizures.
• Many clinical recommendations state that a temperature
less than 102.2 °F (39 °C) in healthy children does not require
treatment. Antipyretics are known to provide comfort to
children and their caregivers.
• Antipyretic treatment for children includes acetaminophen
(Tylenol) 10 to 15 mg/kg every 4 to 6 hours or ibuprofen (Ad-
vil, Motrin) 10 mg/kg every 6 hours.
• Ibuprofen and acetaminophen have both been shown to reduce
fever effectively and safely. Combination therapy has been
shown in some studies to have an added benefit in both reduc-
tion of temperature and comfort without an increase in side
effects, though caution should be taken to avoid dosing errors.
Fever
• Antipyretic therapy for adults and adolescents includes
acetaminophen 650 to 1000 mg orally (PO) every 6 hours
to a maximum of 3 g per day, ibuprofen 200 to 400 mg PO
every 6 hours, or aspirin (ASA) 325 to 650 mg every 6 hours as
needed (PRN) for fever. 15
• ASA should not be used in children due to the risk of Reye’s
syndrome.
• Sponge bathing should be done with tepid water and no
alcohol. Recommendation: sponge bathing and other home
remedies should not be used as sole treatment.
Fever is one of the most common clinical presentations encoun-
tered by primary care physicians and the most common com-
plaint of acute visits for children in the ambulatory or emergency
department setting. Fever is a symptom and one of the most
reliable signs of illness rather than a disease process itself. Most
causes of fever are secondary to acute viral illnesses such as upper
respiratory infections (URIs), which account for 50 million vis-
its to primary care providers annually. Less commonly, bacterial
infections may cause pharyngitis, otitis, sinusitis, pneumonia, and
urinary tract infections (UTIs). A cost-­effective, evidence-­based
approach using clinical protocols, guidelines, and consensus rec-
ommendations to the diagnosis and management of febrile ill-
ness, including the appropriate use of antibiotic therapy, is the
cornerstone of quality medical care for this presentation. Fever
produces significant anxiety for patients, parents, and health care
providers, which can lead to overtreatment. Typically, fever is
transient and only requires treatment to provide patient comfort.
Another random document with
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“We got her back to bed, and when we were alone she said to me:
‘Flora, I must tell you something. I can tell you now, for I am going to
die, and God has forgiven me! I could not give life to any other soul,
Flora, and I could not die knowing that my sins would be visited on a
poor little baby! No, no—I could not bear that.
“‘They told me, the doctor told me at the hospital—or I dreamed it, on
that terrible night of the operation’, she said. ‘Flora, did you know
that I thought I had a child that night? No, or they told me I did——’
she said, beginning to be frightened again.
“‘Don’t bother your head about it now, Cecily,’ I said. ‘Just get well,
so that when Roger comes back——’
“She shuddered at Roger’s name, and began to get excited.
“‘I will be dead before that, and God will have forgiven me, Flora,’
she said. ‘Ah, you don’t think I was a sinner, but I was! Before I ever
took my marriage vow, I had taken another, when I was only fourteen
years old! Another girl and I at the convent had taken a solemn oath
to God that we would never marry!’”
“Poor child!” breathed Gabrielle’s pale lips, involuntarily.
“Poor child,” Flora echoed, without opening her eyes. Her voice was
so weak that David held water to her mouth, and she drank with
difficulty. “Poor little Cecily! She said that when she had first come to
Wastewater she had no thought of lovers or love in her mind. That
she had been bewildered and astonished at the emotion Roger had
almost at once roused in her, but that she had never thought of it as
love. That all her thoughts and senses had been in a wild confusion,
culminating on the day that he and she drove in to Minford, beyond
Tinsalls, quite simply, and that Roger, who knew the Justice there,
got a special license and they were married.
“That night she went quite simply away from her mother’s room,
expecting to be questioned in the morning. But her mother did not
miss her; Cecily was quietly dressing when her mother awakened
the next day. She said she remembered her vow that day. And when
she came to this part, I thought she was going to die. She said quite
seriously that she had had not one single happy moment since, and I
suppose when Roger laughed at her scruples—as he did laugh—he
broke her heart.
“I told her that no minor child could take a valid vow of that sort, and
that indeed her very marriage might be questioned, since her age
had been given as nineteen. No use! She believed me only enough
to say that no irregularity in her license could possibly make her child
more accursed than she would feel a child of hers to be.
“‘But I understand now—I never had a child—it’s Lily’s child!’ she
said, over and over again, with so much deep thankfulness that I
could only be thankful, too. ‘Lily told me all about it,’ she said, so
humbly and tenderly, ‘and she is no worse a sinner than I—less,
perhaps, for she loved and I did not!’
“I dismissed the nurse that afternoon, as it chanced, and sent for a
nurse we had had from Crowchester, Hannah Rosecrans, a fine girl.
She came the next day, and I told her, naturally, the whole truth, but
that both my poor Lily and Mrs. Fleming must be treated with the
utmost consideration until Mr. Fleming came home.
“Cecily was now all anxiety to get back to Wastewater. She said that
she never wanted to see again the cruel old doctor who had
frightened her so. I explained the situation to him, and presently we
all came back to Wastewater, leaving Carrie behind us simply
because she did not want to come.
“Hannah Rosecrans was engaged to be married, she was with us
only a few weeks, and then went to Australia, where her husband
has become well-to-do. She idolized the baby, and loved Lily, too,
but I suppose, servant-fashion, she gave the other servants to
believe that there was something amiss. Anyway, it was always ‘Miss
Lily’s baby,’ from the very first. Lily had told Margret about her
troubles months before, and I was never in any doubt what Margret
thought.
“As for Cecily, she seemed to think it settled. Our Crowchester
doctor was recalled, but there was nothing he could do except keep
her quiet. She was sinking very fast; she died when Gabrielle was
only seven or eight weeks old.
“Roger got home too late—the day before the funeral—but even then
I thought that any accident might show him the truth. I told myself
that in all this confusion it would only sadden him more. I—I don’t
know now what I thought, or why I did what I did! But Lily and the
baby and Margret had their own suite of rooms, and Roger naturally
paid little attention to them—in his grief for his wife. He saw the baby,
took it for granted she was Lily’s. And I told myself that sometime I
would of course tell him the whole story, or somebody would. He
would meet the old doctor who had attended Cecily, or the doctor
who had attended Lily, in Boston. Or he might run across Carrie, or
Hannah Rosecrans——
“Cecily was buried here where we buried Lily only last spring. Roger
went off on his searches, came home—gray-headed and so
changed!—went off again. And I never told him.
“I had begun it to protect Cecily, to comfort Lily—I never had planned
it; it all seemed to come about of itself, and for the first six years of
her life Gabrielle called Lily ‘Mamma.’ Then Lily became very bad,
and we put her in a sanitarium, and she never knew. And then Will
Fleming, my husband, died, and I thought——
“Fool that I was,” Flora added, after a pause, with infinite fatigue and
a sort of self-contempt in her voice, “I cared for Roger even then—I
cared for him even then. I was widowed, and he twice a widower. He
loved my child, but he loved Gabrielle as well. I could not—I could
not put Cecily Fleming’s child ahead of mine. Roger needed me, he
turned to me for everything. I could not see his little girl—placed
ahead of me—pushing me out of his life——
“I couldn’t!” she said more loudly, choking. “I had given my life to him
—my whole life! He had trampled me under his feet. Gabrielle was
fair—she was like Cecily’s mother—she was a beautiful baby. I knew
he would give his whole heart to her, live for her——
“One day he said that he was going to change his will, make a
generous provision for Lily’s poor little girl, and I was glad. It wasn’t
money that mattered—to me. I would have starved for him. He said
that in case his boy never came back, the little girls should share and
share alike, like sisters, and I was glad. There was never any plan in
what I did—I used to think that any hour might change it, any chance
word! I knew that Roger had written a will in Janet’s day, when Tom
was a baby, and when he might have had half-a-dozen other
children, but after this talk he had a good many interviews with his
lawyer, and I supposed that he had done what he said.
“He was not here very much; I came to believe that he hated the old
place, and me, and Lily, and everything that reminded him that he
had once been young and free with the world at his feet. I used to
think that even if he had found Tom, he would have gone on
wandering. But at last, when he came home, it was to die. He died—
you remember, David, quite quietly and without pain, one summer
day—he had been warned of his heart. He was packing to go off to
Panama, a doctor there had written that there was a young fellow
just answering Tom’s description—with—with whatever it is when a
man loses all memory—amnesia——
“A few days later we read the will. You remember, David, on such a
hot morning, in the library? Sylvia and Gabrielle were playing outside
on the terrace where the hydrangeas are; old Judge Baron had
come down from the city.
“We read the will, and I knew then what I had done. Gabrielle was
not mentioned. Gabrielle was not mentioned! The will stood as it had
stood when he wrote it, when Tom was a baby. Everything,
everything to his child, or children. And there was a codicil, dated
about the time of his last return home, giving everything, everything,
to Sylvia, in case Tom did not come back!
“My God, my God——” Flora whispered, under her breath, and lay
still.
“I had wanted it all my life, and now I had it,” she said, after a while,
in a voice that was weakening, weakening from moment to moment,
and yet full of passion and fire still. “I had it all. Judge Baron went
away, David went away, I was alone with Sylvia and little Gabrielle,
and Wastewater was mine. I remember, in the first long warm
afternoon, that I walked slowly through it, from room to room, and
thought that I had survived them all—Uncle Tom, Roger, Janet,
Cecily, Will—all, all the Black Flemings gone except me! I had only to
keep silent, and my child would be rich.
“I think that’s all,” she added, opening her sunken dark eyes and
fixing them steadily upon David’s face. “That explains it all, doesn’t
it? I have lived in fear. I knew the old doctor was dead, but I used to
lie in the nights imagining that he had happened to tell someone—
someone who was drawing nearer and nearer to my life every
moment. Hannah Rosecrans, the Carrie we had in Boston, the
doctor Lily had, whose very name I can’t remember—they all knew!
Any day might have brought them back to me with their questions.
“I used to imagine that I might go to jail! But I never was anything
else but in jail all my life long!”
 CHAPTER XIX
She stopped. And after a long minute of silence the young persons
looked at each other. Tom had been sitting throughout in a low chair
with his hands locked; now he merely grinned nervously and
shrugged. David’s face was stern and grave; he had folded his arms
and had been staring ahead of him with a faint frown. Now his eyes
moved about the circle and returned to space. Sylvia’s vivid dark
face with its white, white skin was drained of colour, her eyes looked
tortured, and she was breathing fast. As she knelt beside the bed,
she half supported her mother upon her arm, her anxious and
stricken face close to the leaden, ghastly face upon the pillow.
Gabrielle had been kneeling, too, as she listened. But at the end she
rose and walked to the little window.
Outside, in the winter dusk, lay the soaked, blackened ruins of the
old stables, those clean big airy stables that Gabrielle had so loved
as a little girl. Nearer, against the angle of the house, lay the wreck
of the windmill, the great rusty hoops and singed wood piled almost
as high as the window. Beyond all were the bare winter woods,
looking desolate and forlorn in the cool gray light, and on the right
brimmed and lowered the steely surface of a cold and unfriendly sea.
As Gabrielle stood there, her weary heart and mind whirled hither
and thither by a hundred conflicting thoughts, in a very storm of pity
and pain, the island lights suddenly pricked through the dove-gray of
the gloom and flashed their pinkish radiance against the gaining and
prevailing shadows. The girl’s thoughts travelled to them idly—she
thought of little ships cutting their way through the trackless waters,
and dark-faced, rough men twisting the spokes of the little wheels
and peering out across the waves to find that steadily pulsating flash.
Somebody had lighted a light in the room behind her; she saw her
own reflection, slender, aureoled, against the dark night. David
touched her arm.
A sudden bitter need of tears possessed her, and her breast swelled.
But she only raised heavy eyes to his questioningly, and bit her lip to
steady it.
“Aunt Flora wants to speak to you, Gay.” The girl could tell by David’s
tone that he had said it before. He gently turned her toward the bed.
She looked bewilderedly at Tom, who was busy at the lamp, and at
Sylvia, who stood at the foot of the bed. Like a person in a dream
she went slowly toward Flora, and knelt down beside her.
Flora reached out hard and anxious fingers and gripped the girl’s
hand.
“I told David this yesterday—he told you and Tom—he was to tell you
—when the fire came——” Flora whispered.
“He did tell us.” Gabrielle’s beautiful voice sounded childish and
husky in contrast to the other weak voice. “But I thought—I thought
that—my mother—Lily was still my mother, and that Uncle Roger
was my father—that I had no right to call him father. It seems”—her
lips shook again—“it seems that I might have had—a father——” she
faltered. Her voice thickened and stopped. She raised her eyes
appealingly, almost apologetically to David, who was watching
closely. “I never—had—any one,” she said, with suddenly brimming
eyes.
Flora spoke, and immediately afterward, in a strange muse that was
not hearing, Gabrielle heard Sylvia give a sort of cry, and then David
leaned over her and said tenderly:
“Gay—she is very ill, dear. If you can——?”
“If I can—what—David?” she repeated, confused, her beautiful eyes
wide and anxious.
“She wants you to forgive her, Gabrielle,” David answered.
Gabrielle still appeared bewildered; she looked from one face to
another.
“Yes, I will, of course I will,” she said, quickly and simply.
“Then tell her so, Gabrielle.”
Gabrielle bent her gaze upon her aunt’s sunken face, a blot against
the white pillows, and Flora fixed upon her the tragic look of her
darkening eyes.
“I am sorry, Aunt Flora,” Gabrielle stammered, in tears. “I know—I
know how hard it must have been for you. I am so sorry.”
“You will forgive me, Gabrielle?” Flora whispered, feverishly. “In all
the years to come you will not hate me? You have grown to be a
lovely woman—I did not harm you. I might have harmed you—but it
was Sylvia, in the end, who paid for what I did.”
“I will never hate you,” Gabrielle said, slowly and steadily, like a child
repeating a lesson.
“It was because I loved him so,” said Flora’s drawn, dark mouth, in a
whisper. She sank back, seemed to be sinking away from earth and
the things of earth altogether. “God bless you, Gabrielle, you have
made it easy for me to die,” she added, in the mere breath of a
voice.
“I’m—so—sorry!” Gay said, with a great sob. And she buried her
face against the coverlet and burst into crying. “I’m so sorry that he
was unkind to you—and that you could not forgive him and forgive
me!” she sobbed. “We might have been—we might all have been so
happy!”
“We might have been so happy,” Flora’s lips repeated. No other
muscle of her bloodless face and shut eyes moved. “God bless you,
Gabrielle,” she whispered again, as Gabrielle, drawn away by
David’s hand, stopped to lay a wet cheek against hers and kiss her
in farewell.
The girl, halfway to the door, and hardly conscious of what she was
doing, suddenly wrenched herself free and went back to the bed.
She fell on her knees, and catching the languid dark hand, put it to
her lips.
“Aunt Flora, indeed I forgive you!” she said, weeping, “from my heart.
I am so sorry you were so unhappy—that they all hurt you and failed
you so! Dear Aunt Flora——”
Sylvia was on her knees on the other side, and crying as bitterly as
Gabrielle, when David led the younger girl away. He and Margret
established her upon a downstairs sofa, with cushions and covers
before the fire, and she lay there in a dreamy state, not talking,
hardly thinking, as the strange panorama of the last twenty-four
hours wheeled through her weary head. She saw Flora only once
again, and that was at the end, at seven o’clock.
At ten Tom drove them to Crowchester and they boarded the Boston
train; Sylvia veiled and clinging tightly to Tom’s arm, Gabrielle and
old Margret guiding them through the interested, warm train to the
privacy of their drawing room.
Gabrielle’s last look at Wastewater had shown her only bare trees,
blackened masses of ruins darker than the prevailing dark, open
levels where the stately walls had been. A cold moon had been
shining brightly upon the sea, had thrown the shadows of leafless
bushes in a lacework across the bare brown space of the lawn, and
against the steady rush and retreat of the short waves she had heard
the tumbling cascading sound of some bit of wall collapsing upon the
general collapse. Toward the distant west wall, beyond the woods,
the changed perspective had left a long vista free, and Gabrielle
could see the white gravestones in the moonlight.
Graves and ruins, ashes and bare branches, and beside them the
unchanged, restless sea, and above them the unfeeling moonlight.
The child of Wastewater looked back with a great gravity, a great
solemnity in her heart. There had been laughter here, music and
voices. Wastewater had had a housewarming, more than a hundred
years before, when beautiful women, in the capes and high-waisted
gowns of the Empire days, had been driven in jingling great coaches
all the way from Boston City to dance and rejoice with the young
master of the mansion.
There had been a first Roger, in the buff and blue of the Revolution,
Colonel Fleming, as black and as handsome as any of them, and
there had been his son Tom, the good-hearted Tom who had come
all the way to Brookline to find a cousin’s disconsolate little widow,
with her sewing machine, and her girl babies, and offer them a
home.
And there had been Tom’s son Roger, handsomest and most
dashing of them all—David’s young mother, who was to win his
heart, and that shadowy little Cecily, who must now be “mother” in
Gabrielle’s thoughts.
Aunt Flora always watching jealously; Aunt Lily tearful and singing
her romantic little songs; gallant little Tom reading his sea stories on
the old nursery window-sill; dark little proud Sylvia with her glossy
curls; baby Gay herself, wistful and alone; they all seemed to pass
before the girl’s eyes in a long and haunting procession, crying as
they went that they had always failed, even here, in all this wealth
and beauty, to find happiness and peace!
“I will be happy,” Gabrielle had sworn to herself solemnly, frightened
at the history of the place. “I will try never to be proud or jealous or
cruel. We are Flemings, we four—and I as much a Fleming as any
one of them now, and we must not make their mistakes! God helping
us,” she thought, remembering the little nun who had years ago read
the Sermon on the Mount to a class of inattentive little girls so many
times, “we will all be good, and meek, and merciful, and some day—
years and years from now—we will come back to Wastewater again
and rebuild it.
“Good-bye, Wastewater!” she had whispered, leaning back to look
through the glass window of the motor car. And from beyond the
ruins, the ashes, the bare garden, and the moonlit sea, the island
lights had flashed her an answer.
 CHAPTER XX
It was more than a long year later that David Fleming, driving the
car that Sylvia had ordered with such happy confidence before that
long-awaited twenty-first birthday, left Crowchester, and followed the
familiar road along the cliffs.
The spring was early, and the sweetness of it was already in the air;
there were patches of emerald grass in sheltered places, and all the
rich warm milky odours of turned earth and fruit blossoms, new
leaves and the first hardy lilacs. Babies in sheltered coaches were
airing along the little streets of Keyport, and if the restless little
breezes and the sunless shadows were chilly, in the sunlight there
was a delicious warmth.
The familiar dips and turns of the road were all like so many
welcoming faces to David, and when he reached the boundaries of
Wastewater he might almost have fancied, for a moment, that the old
order of things had remained unchanged, that back of that barrier of
great trees, now trembling into tiny dots of palest green, he might
indeed find the grim dark building, the shuttered windows, the dank
unhealthy shrubs and paths that had been the first home of his
recollection.
The brick walls and the iron gates, more deeply bedded than ever in
fallen leaves and mould, were unchanged, but the road between
them, so many years unused, had been somewhat cut by wheels,
and had been churned into mud. It stood open, but David left his car
outside, got out and turned his back to the land for a moment,
standing staring out to sea, as he had done upon that autumn day
more than two years ago, that dreary, dark October day when
Gabrielle had first come home.
He remembered, as his eyes idly followed the scrambling path down
between the rocks and the bare mallow bushes to the shore, the
muggy smells that had always assaulted his nostrils when the big
side door of Wastewater had been opened, the smell of distant soup
bones, dust, horsehair furniture, decaying wood, stifling coal fires
that smoked. He remembered his aunt, rigid and stern, before the
fire, her apprehensive, nervous eyes always moving behind him
when he entered the room, and searching there for some menace
always feared and never realized. He remembered the lamps, the
antimacassars, the booming voices of the maids in the gloomy halls.
And then Gabrielle, in her velvet gown, with her big, starry eyes.
Gabrielle, so young and so alone, met by such staggering blows,
such bitter truths. Gabrielle watching Sylvia’s youth and happy
fortune so wistfully, bearing her own sorrows and burdens with her
own inimitable childish courage and dignity.
What a time—what a time! the man mused, his breast rising on a
great sigh, as he shook his head slowly. Sylvia’s majority, and then
Tom’s return, Aunt Flora’s stupefying revelation as to Gay’s
parentage, and then the last scene—or almost the last—when he
had gone upstairs to tell them—Gabrielle and Tom, that they were
brother and sister, and the great wind and the fire had trapped them
there.
So that had been the end of Wastewater, with these four young
persons, all Flemings, flying for their lives through the night, and
Aunt Flora, who had spent all her life there, killed by the falling of all
her moral and material walls in one terrible crash. She had lain for
almost twenty-four hours in John’s dismantled house, without pain of
body, and in a lulled state even of mind, but she had been dying
none the less. David had reviewed a hundred times the dark and
forbidding afternoon, the ugly red of the sunset, as it shone upon the
walls, and the memory of Aunt Flora’s sunken face against the
pillows, the memory of her monotonous, weary voice.
The last of her generation, that stormy and ill-governed generation
whose passions and weaknesses had filled the whole house with
tragedies for so many years, she had died very quietly, quite as if
going to sleep, before the ashes of the old place had been cold.
Sylvia, beautiful, twenty-one, her own life as truly in ruins and ashes
about her, had been kneeling beside her mother at the end, the
doctor standing gravely near, and David himself watching them all
with that strange quality of responsibility that seemed to be his
destiny where each and every one of them was concerned.
Afterward, Tom had taken the girls in to Boston, where Sylvia, ill from
shock and sorrow, had been left in the care of Gabrielle and a nurse,
while Tom and David came back to Wastewater for the funeral.
David, reaching this point, turned back and looked across the old
garden, to find the glint of headstones far up the northwest corner of
the estate, beyond the woods, and under a fountain of delicate blue-
green willow-whips.
Much of the garden was left after only one season’s neglect, he
mused, and could be reclaimed. There were healthy-looking roses,
and the splendid hedge of lilacs was already bursting from hard
brown buds into white and lavender plumes. The conifers looked
clean and fresh in their new tips, even the maples and elms were
magnificent as ever.
An odd new look of something like pioneer roughness had been
given the place, however, by the raw wood-piles. Gay’s one
stipulation, David smiled to remember, in one of the few allusions
she had made to the subject, had been in reference to the heavy
evergreen shrubbery close to the house. Mightn’t—she had put it so,
although all this land was hers now—mightn’t a lot of those ugly old
pines and cypresses come down?
Down they had accordingly come, to be chopped and piled into
substantial stacks against some coming winter. Also stacked and
piled were the bricks that had been Wastewater, the thousands and
hundreds of thousands of bricks, that had been scraped and aligned
into long solid blocks.
Some day, David mused, there would be a home here again. But
when, the young persons most concerned had not yet definitely
stated. He sighed as he thought of them, and smiled above the sigh.
A start had been made, at least. There was a handsome building
already standing; a long low barn of friendly warm clinkered brick,
with the wide new doors of a garage at one end, and at the other,
across an arch, beyond which cows and horses might be fenced
some day, was a homely, comfortable cottage, of the type that faces
a thousand English lanes, steep roof cut by white-curtained dormers,
latticed deep windows against which vines were already trained, and
a hooded doorway with a brass knocker.
An Airedale, whirling about the corner of the building with a wild
flourish, leaped upon David in welcome, and immediately curled
himself rapturously in the short film of the grass, with all four feet in
the air, writhing in puppy ecstasies.
“Here, here, Ben!” David said, laughing. “Grow up! It’s ridiculous to
see a dog of your age acting that way!”
But he was rubbing and tousling the rough head affectionately, none
the less, as he called, “Etta! John!”
In answer Etta, John’s wife, appeared with an undisturbed smile. For
the months of building last fall, and again this spring, Mr. David had
been living in his little Keyport farmhouse and might be expected
here at almost any minute to inspect and approve. Etta herself had
watched so much of the re-building with secret contempt. It seemed
odd, when one could afford a nice square plastered house, and a
corrugated iron barn, to waste twice as much money on what John
considered “monkey shines.” But Miss Gabrielle and Miss Sylvia and
Mr. Tom had all been away for more than a year now, in California
and Mexico and Panama, and now it was Central America, and dear
knows what it’d be next, and consequently Mr. David and his friend
Mr. Rucker had had it all their own way.
Etta had no objection to Mr. Rucker, who was always so kind and
polite, and funny, too, if you always understood just what he meant,
but she could not understand why he should drag in talk about
Swedish farmhouses and Oxford.
“I don’t know anything about Oxford,” Etta had more than once
commented to her husband, “but I do know that the Swedes all get
here as fast as they can, and why any one’d want to bring their
clumsy-looking old barns after them beats me! Mr. Rucker was
showing me the pitchers in a book; ‘It looks like something a child
would make with blocks, if you’d ask me!’ I told him.”
“I hope when they build a house it’s going to look decent,” John
might answer, uneasily. “I don’t know what better they’d want than
three stories with plenty of bay windows and porches. I seen one
pitcher Mr. David had in a book with all the roofs kinder sloping down
into the garden, and the windows all different sizes and levels. Mr.
Rucker says he has some old leaded windows from a bar-room—
that’s what he said—for the liberry. I had Davis, over to the Lumber
Company, send him a catalogue, and mark all the new doors and
windows with a blue pencil, but I don’t know if he got it.”
To-day David gave Etta an opportunity for criticism when he said
cheerfully, as she somewhat reluctantly accompanied him about the
place:
“How’s the house, Etta—comfortable?”
“Oh, we’re quite comfortable, thank you,” Etta answered, primly, in a
faintly complaining tone, “and John’s got the Eyetalians engaged to
start the side garden anyway before the folks get back. But here’s
the thing that I’ll never get through my head,” Etta added, with the
readiness of an already well-aired grievance, as she looked up at the
wide archway and its casement windows above; “it don’t seem
sensible to have that arch, or gate, or whatever you call it, making
the barn and the house into one. As far as needing the room goes,
we’ll never need it, for John would no more think of going through
that way for the hay than flying over the moon. I was thinking it would
look handsomer to have the barn separate—and while the men are
right here, and before Miss Gabrielle gets home to look at the plans
for a house, and dear knows when that will be now!—why, they could
tear out that arch real easy, and smooth the brick up so that it’d
never show—and it does seem as if it’d be more Christian—more
like the way other places look—places like the Smiths’, over to
Tinsalls, that have millions of dollars, but their house looks so neat
and square——”
“Ah, they’ve got the stable foundations started,” David said, in
satisfaction, paying no attention to Etta’s remarks.
“Oh, yes, sir, they got the cement in day before yesterday,” Etta,
diverted, answered, in the same placid whine.
“That’s fine,” David said, nodding to the various workmen as he
walked about. “Room for four cows and about that many horses, and
some day we’ll put a chicken run on that end.”
“Do they say when they’ll be coming back, sir?” Etta asked.
“Any time this summer, I suppose,” David said. “Mr. Tom is quite
himself again—too well, in fact, Miss Sylvia wrote. I think she and
Miss Gabrielle would have been glad to come straight home from
San Francisco, but Mr. Tom saw the masts of ships again, and that
was enough. He wired they wanted me to go around the world with
them, but eventually they seemed to have compromised on Panama.
I’ve not had letters yet, but in a telegram a few days ago—I told you
that?—there was some talk of Central America.”
“Dear me,” said Etta, who always made this remark in any pause,
“haven’t there been changes? That grand old house—John says it’d
cost a million dollars to rebuild it now—it does seem such a pity it
had to burn down!”
“The insurance,” David said, consolingly, “will more than build a
much prettier and more homelike Wastewater.”
“Oh, I don’t know,” Etta said, with the relished pessimism of an old
servant. “I was wondering if Mr. Rucker had seen them pretty
plastered houses over to the Crowchester Manor Estates?” she
asked, adroitly.
David did not answer. He looked at the mud-spattered and torn blue-
print that was anchored from the coquettish spring breezes upon a
plank with two brick-bats, murmured to the contractor, suggested,
approved.
It was easy for his thoughts to find Gabrielle at Wastewater, for they
were almost all of her in these days, and it was here that she had
spent her life, except her school years. David had no recollection of
her in any other setting. To-day, as always, she seemed to be beside
him, walking through the strangely altered spring garden, talking with
him of the changes to be.
She had borne herself, he had thought, with his affectionate quiet
pride in her carrying as ever an undercurrent of pain—she had borne
herself in the trying time of readjustments and changes better than
all of them. There was a native dignity, a fineness about her, that
made it possible for her apparently to forget herself entirely.
As he remembered her, in the few weeks that had intervened
between her departure with Tom and Sylvia for the West, in old
Margret’s care, it was difficult to recall any special demonstration of
her own feelings at all. Sylvia had been actually if not seriously ill,
Tom had suffered a dangerous relapse after the strain and exposure
of the night, but Gay had been just her usual self. David had had a
thousand cares: first to establish them temporarily in a comfortable
hotel, then to commence the endless business of placing Gabrielle in
her rightful position, with all it involved in the matter of taxes,
transfers, legal delays of every sort.
He had written to the far-away Hannah Rosecrans in Australia, and
had had a prompt and satisfactory reply. Hannah was Mrs. Tarwood,
now, with children of her own. She gladly and unsuspiciously
supplied a hundred details: the Fleming baby’s first nurse’s name at
the big hospital, the name of a young doctor who had more than
once come to see little Gabrielle in her first delicate weeks of life.
Through these and Flora’s other clues David established the matter
legally beyond all doubt, and Tom simplified the question of property
division by being eager to reserve about only one fifth of his father’s
estate for himself, giving his half-sister everything else. Wastewater,
the jewels, this piece of property, that other, this stock and those
bonds, everything, in short, about which division might have
presented the slightest difficulty, Tom would have impatiently
discarded in her favour. He was going to die anyway, he would
remind them.
Beyond all this, David had Sylvia’s inheritance to handle. Flora had
left a will, but it was superseded by an urgent note to her daughter,
written at the time when Sylvia was supposed heiress to the whole
Fleming fortune, begging her to make over her own money to
Gabrielle.
Sylvia, hysterical and sensitive and unreasonable, had still persisted
that this must be done; Gay—she protested in floods of shamed
tears—had been wronged long enough! No, it must be all, all Gay’s,
and she, Sylvia, would go forth into the world penniless, and make
her own way—she would be happier so.
It had been Gay, patient and serious, in her new black, who had
talked her into a healthier frame of mind. Gay had sat beside her
cousin’s bed, smiling, talking occasionally, interesting Sylvia in the
various phases of the business as they had come up, had managed
both invalids and the whole comfortable suite, and had joined David,
to affix a signature or witness a deed, as quietly as if this earthquake
had touched her personally not at all.
Most admirable, he thought, had been her attitude with Tom. From
the strange, disorganized winter day of Aunt Flora’s death, Gay had
been quite simply, affectionately, and appreciatively Tom’s little sister.
There had been no scenes, no hysteria, no superfluous words; David
did not even suppose that the sister and brother had discussed the
subject. Immediately, and with a youthful and almost childish grace
that David, remembering, would recall with suddenly blinking eyes,
she had adopted big, clumsy, unpolished Tom. In three days, quite
without awkwardness, if with a sometimes slightly heightened colour,
he had heard her speak of “my brother” to doctors, nurses, waiters in
the hotel.
She had carried Tom, he realized now, by storm, by the sheer force
of her own extraordinary personality. If Tom had ever been in any
doubt as to the fashion of recommencing their friendship along these
wholly altered lines, Gabrielle had instantly dispelled it.
More, she had given Tom as a brother ten times the visible affection
and confidence that she had been willing to give him in any other
relationship. Gabrielle had been afraid to be too friendly before. Now
she was free to laugh with him, to spoil him, to tease him, to sit on
the edge of his bed and hold his big, hard hand while she recounted
to him her daily adventures.
And Tom had proved quite unconsciously, by his pathetically eager
and proud acceptance of this new state of affairs, that it was her
companionship, her sympathy he had wanted. He had wanted to be
a little needed, a little admired, to be of some consequence to David,
to the admirable Sylvia, and lastly, to inconsiderable and neglected
little Gabrielle.
He had seized upon his half-brotherhood with her as he had never
developed exactly the same relationship with David. Indeed, so
consummately wise had been this child’s—for David thought of her
as scarcely more than a child—this child’s handling of the situation,
that within a week of the change Tom’s tone had actually taken on
the half-proud, half-chiding note of an adoring elder brother, and
David had seen in his eyes the pleased recognition of the fact that at
least no one else was, or could be, Gabrielle’s “family” but himself.
Tom’s condition appearing to be supremely unsatisfactory, there had
immediately been talk of southern California or Florida for the winter.
For Sylvia, who was strangely shaken, quiet, and unlike herself even
when physically well again, it seemed a wise solution, too. Gabrielle
was of course to accompany her brother, and David must follow as
soon as all their complicated affairs permitted.
Saying good-bye to the little black-clad group, when he had escorted
them as far as Chicago, David had returned somewhat sadly to his
duties as doubly, trebly an executor, his canvases, and the lonely
painting of the first snows. And after that the months had somehow
slipped by in a very chain of delays and complications: upon the only
occasion when David had actually been packed and ready to start
for the West, a telegram from his closest friend, Jim Rucker, or rather
from Jim’s wife, in Canada, relative to an accident, illness, and the
need of his help, had taken him far up into the Winnipeg woods
instead.
Had the three Flemings been in La Crescenta, high and dry above
ocean and the valleys of southern California, where they had at first
quite established themselves, with a piano and a garden and a
telephone, David might have joined them during the second summer.
But by this time Tom was entirely well again, perfectly able to live in
the East, winter and summer if he liked, “but catch me doing it,”
wrote Tom, in his large sprawling hand, and the travellers had gone
into Mexico.
“Do for Heaven’s sake be careful, Gay,” David had written anxiously.
“You appear to be the brains of the expedition. You may get into hot
water down there!”
“Sylvia, on the contrary, is the brains of the expedition, as you so
elegantly phrase it,” Gabrielle had answered, cheerfully, “and as to
getting into trouble—no such luck!”
Then they were in San Francisco again, and David, with a muffled
hammering going on steadily in his heart when he thought of seeing
Gay again, had been expectant of a wire saying that any day might
find them turning eastward. But no, for Tom had caught sight of all
the huddled masts in the San Francisco harbour, the mysterious
thrilling hulls that say “Marseilles” and “Sydney” and “Rio de
Janeiro,” and he had been all for Australia—all for South America—
had compromised finally upon Panama.
That was two months ago. Now, perhaps still feeling that the late
New England spring would be chilly, they were apparently off for
Guatemala and Honduras.
David could school his heart the better to patience because he had
no hope. No hope even in her obscure little friendless days really of
winning Gabrielle, and less hope now. His attitude toward all women,
as he himself sometimes vaguely sensed, was one of an awed
simplicity; they seemed miraculous to David, they interested him
strangely and deeply, as beings whose lightest word had a
mysterious significance.
If he had once loved Sylvia dearly, loyally, admiringly—and he knew
that for almost all her life he had—then what he felt toward Gabrielle
was entirely different. There was no peace in it, no sanity, no
pleasure. It burned, an uncomfortable and incessant pain, behind
every other thought; it penetrated into every tiniest event and act of
his life.
The mail to David, nowadays, meant either nothing or everything.
Usually it was nothing. Once a month perhaps it glowed and