conn's current therapy 2012 - e. bope, r. kellerman (saunders, 2012)

Aring, MD Associate Program Director, Family Medicine Residency, TheOhio State University College of Medicine; Assistant ProgramDirector, Family Medicine Residency, Riverside MethodistHo

CURRENT THERAPY

2012

CURRENT THERAPY

2012

EDWARD T BOPE, MD

Chief of Primary Care

Columbus VAAssistant Dean for VA Medical Studentsand Clinical Professor, Family Medicine

The Ohio State UniversityFaculty, Riverside Family Practice Residency Program

Riverside Methodist Hospital

Columbus, Ohio

RICK D KELLERMAN, MD

Professor and ChairDepartment of Family and Community MedicineUniversity of Kansas School of Medicine–Wichita

Wichita, Kansas

Latest Approved Methods of Treatment for the Practicing Physician

1600 John F Kennedy Blvd.

Ste 1800Philadelphia, PA 19103-2899

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NoticesKnowledge and best practice in this field are constantly changing As new research andexperience broaden our understanding, changes in research methods, professional

practices, or medical treatment may become necessary

Practitioners and researchers must always rely on their own experience and knowledge inevaluating and using any information, methods, compounds, or experiments describedherein In using such information or methods they should be mindful of their own safetyand the safety of others, including parties for whom they have a professional responsibility.With respect to any drug or pharmaceutical products identified, readers are advised tocheck the most current information provided (i) on procedures featured or (ii) by themanufacturer of each product to be administered, to verify the recommended dose orformula, the method and duration of administration, and contraindications It is theresponsibility of practitioners, relying on their own experience and knowledge of theirpatients, to make diagnoses, to determine dosages and the best treatment for eachindividual patient, and to take all appropriate safety precautions

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ISBN: 978-1-4557-0738-6

Acquisitions Editor: Kate Dimock

Developmental Editor: Joan Ryan

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Designer: Steven Stave

Printed in the United States

Charles S Abrams, MD

Associate Chief, Division of Hematology-Oncology, University of

Pennsylvania School of Medicine; Staff Physician, Division of

Hematology-Oncology, University of Pennsylvania Medical

Center, Philadelphia, Pennsylvania

Platelet-Mediated Bleeding Disorders

Mark J Abzug, MD

Professor of Pediatrics (Infectious Diseases), University of

Colorado–Denver School of Medicine; Medical Director, The

Children’s Hospital Clinical Trials Organization, The Children’s

Hospital, Aurora, Colorado

Viral Meningitis and Encephalitis

Horacio E Adrogue´, MD

Medical Director, Pancreas Transplant Program and Medical

Director, Methodist Transplant Network, The Methodist

Hospital Transplant Center, Houston, Texas

Hypertension

Tod C Aeby, MD

Residency Program Director, Generalist Division Chief,

Department of Obstetrics, Gynecology, and Women’s Health,

University of Hawaii John A Burns School of Medicine,

Honolulu, Hawaii

Uterine Leiomyomas

Lee Akst, MD

Assistant Professor, Department of Otolaryngology, Johns

Hopkins University, Baltimore, Maryland

Hoarseness and Laryngitis

Mahboob Alam, MD

Staff Cardiologist, Kennedy Veterans Affairs Medical Center;

Assistant Professor, University of Tennessee Health Sciences

Center, Memphis, Tennessee

Section on Endocrinology and Genetics, Program on

Developmental Endocrinology and Genetics, Eunice Kennedy

Shriver National Institute of Child Health and Human

Development, National Institutes of Health, Bethesda,

Heart Block

Emmanuel Andre`s, MD, PhD

Service de Me´decine Interne, Diabe`te et Maladies Me´taboliques,Clinique Me´dicale B, Hoˆpital Civil–Hoˆpitaux Universitaires deStrasbourg, Strasbourg, France

Pernicious Anemia and Other Megaloblastic Anemias

Gregory M Anstead, MD

Associate Professor of Medicine, University of Texas HealthScience Center at San Antonio School of Medicine; Director,Immunosuppression and Infectious Diseases Clinics, SouthTexas Veterans Healthcare System, San Antonio, TexasCoccidioidomycosis

Aydin Arici, MD

Professor, Department of Obstetrics, Gynecology, andReproductive Sciences, Yale University School of Medicine,New Haven, Connecticut

Abnormal Uterine Bleeding

Ann M Aring, MD

Associate Program Director, Family Medicine Residency, TheOhio State University College of Medicine; Assistant ProgramDirector, Family Medicine Residency, Riverside MethodistHospital, Columbus, Ohio

Fever

Isao Arita, MD

Chair, Agency for Cooperation in International Health–

Kumamoto, Kumamoto City, JapanSmallpox

Cecilio Azar, MD

Associate in Medicine, Division of Gastroenterology, Department

of Internal Medicine, American University of Beirut MedicalCenter, Beirut, Lebanon

Bleeding Esophageal Varices

Masoud Azodi, MD

Associate Professor, Division of Gynecology/Oncology, YaleUniversity School of Medicine, New Haven, ConnecticutEndometrial Cancer

Adrianne Williams Bagley, MD

Pediatrician, Lincoln Community Health Center, Inc., Durham,

North Carolina

Pelvic Inflammatory Disease

Justin Bailey, MD, FAAFP

Clinical Instructor, Department of Family Medicine, University of

Washington, Seattle, Washington; Family Medicine Residency

of Idaho, Boise, Idaho

Nausea, Vomiting, Gaseousness, and Dyspepsia

Federico Balague´, MD

Privat Docent, Rheumatology, Medical School, Geneva

University, Geneva, Switzerland; Adjunct Associated Professor,

Orthopedics, New York University, New York, New York;

Me´decin Chef Adj Service de Rhumatologie, HFR-Hoˆpital,

Cantonal Fribourg, Switzerland

Spine Pain

Ashok Balasubramanyam, MD

Professor of Medicine, Division of Diabetes, Endocrinology, and

Metabolism, Baylor College of Medicine, Houston, Texas

Diabetes Insipidus

Arna Banerjee, MD

Assistant Professor of Anesthesiology and Surgery, Department of

Anesthesiology and Critical Care and Department of Surgery,

Vanderbilt University Medical Center, Nashville, Tennessee

Delirium

Nurcan Baykam, MD

Associate Professor of Infectious Diseases, University of Ankara

Faculty of Medicine; Staff, Infectious Diseases and Clinical

Microbiology Clinic, Ankara Numune Education and Research

Hospital, Ankara, Turkey

Brucellosis

Meg Begany, RD, CSP, LDN

Neonatal Nutritionist; Nutrition Support Service Coordinator,

Newborn/Infant Intensive Care Unit, The Children’s Hospital of

Philadelphia, Philadelphia, Pennsylvania

Normal Infant Feeding

David I Bernstein, MD

Professor of Medicine and Environmental Health, University of

Cincinnati College of Medicine, Cincinnati, Ohio

Hypersensitivity Pneumonitis

John P Bilezikian, MD

Professor, Department of Medicine, Columbia University College

of Physicians and Surgeons; Attending Physician, New

York-Presbyterian Hospital, New York, New York

Primary Hyperparathyroidism and Hypoparathyroidism

Federico Bilotta, MD, PhD

University of Rome La Sapienza, Rome, Italy

Hiccups

Natalie C Blevins, PhD

Assistant Professor of Clinical Psychology in Clinical Psychiatry,

Department of Psychiatry, Indiana University School of

Medicine, Indianapolis, Indiana

Cancer of the Skin

Mary Ann Bonilla, MD

Assistant Clinical Professor, Columbia University College ofPhysicians and Surgeons, New York, New York; AttendingPhysician, St Joseph’s Regional Medical Center, Paterson, NewJersey

Neutropenia

Zuleika L Bonilla-Martinez, MD

Wound Healing Fellow, Department of Dermatology andCutaneous Surgery, University of Miami Miller School ofMedicine, Miami, Florida

Reproductive Endocrinology, University of Cincinnati MedicalCenter, Cincinnati, Ohio

Menopause

Mark E Brecher, MD

Adjunct Professor, Department of Pathology and LaboratoryMedicine, University of North Carolina at Chapel Hill School ofMedicine, Chapel Hill, North Carolina; Chief Medical Officerand Senior Vice President, Laboratory Corporation of AmericaHoldings, Burlington, North Carolina

Therapeutic Use of Blood Components

Pyelonephritis

Patrick Brown, MD

Assistant Professor of Oncology and Pediatrics, The JohnsHopkins University School of Medicine; Director, PediatricLeukemia Program, Sidney Kimmel Comprehensive CancerCenter at Johns Hopkins, Baltimore, Maryland

Acute Leukemia in Children

Richard B Brown, MD

Professor of Medicine, Tufts University School of Medicine,Boston; Senior Clinician, Baystate Medical Center, Springfield,Massachusetts

Toxic Shock Syndrome

vi

Instructor, Department of Obstetrics and Gynecology, University

of Pennsylvania School of Medicine; Staff, Hospital of the

University of Pennsylvania, Philadelphia, Pennsylvania

Menopause

Diego Cadavid, MD

Consultant in Immunology and Inflammatory Diseases,

Massachusetts General Hospital, Boston, Massachusetts

Relapsing Fever

Grant R Caddy, MD

Consultant Physician and Gastroenterologist, Ulster Hospital,

Belfast, Northern Ireland

Cholelithiasis and Cholecystitis

Thomas R Caraccio, PharmD

Associate Professor of Emergency Medicine, Stony Brook

University Medical Center School of Medicine, Stony Brook,

New York; Assistant Professor of Pharmacology and

Toxicology, New York College of Osteopathic Medicine, Old

Westbury, New York

Medical Toxicology: Ingestions, Inhalations, and Dermal and Ocular

Absorptions

Enrique V Carbajal, MD

Associate Clinical Professor of Medicine, University of California–

San Francisco School of Medicine, San Francisco, California;

Department of Medicine, Veterans Affairs Central California

Health Care System, Fresno, California

Premature Beats

Steve Carpenter, MD

Associate Professor, Baylor College of Medicine, St Luke’s

Episcopal Hospital, Houston, Texas

Hodgkin’s Disease: Radiation Therapy

Petros E Carvounis, MD, FRCSC

Assistant Professor, Cullen Eye Institute, Baylor College of

Medicine; Chief of Ophthalmology (interim), Ben Taub General

Hospital, Harris County Hospital District, Houston, Texas

Uveitis

Donald O Castell, MD

Professor of Medicine, Division of Gastroenterology and

Hepatology, Medical University of South Carolina, Charleston,

South Carolina

Gastroesophageal Reflux Disease

Alvaro Cervera, MD

University of Barcelona, Barcelona, Spain; National Stroke

Research Institute, Heidelberg Heights, Victoria, Australia

Ischemic Cerebrovascular Disease

Lawrence Chan, MD

Professor of Medicine, Rutherford Chair, and Division Chief,

Diabetes, Endocrinology, and Metabolism, Baylor College of

Medicine; Chief, Diabetes, Endocrinology, and Metabolism,

St Luke’s Episcopal Hospital, Houston, Texas

Dyslipoproteinemias; Primary Aldosteronism

Miriam M Chan, BSc Pharm, PharmD

Clinical Assistant Professor of Family Medicine, College ofMedicine and Public Health, The Ohio State University,Columbus, Ohio; Clinical Assistant Professor of Pharmacy, TheOhio State University College of Pharmacy, Columbus, Ohio;

Adjunct Professor of Pharmacy, Ohio Northern University, Ada,Ohio; Program Director of Research and EBM Education,Medical Education, Riverside Methodist Hospital, Columbus,Ohio

Herbal Products; New Drugs in 2010 and Agents Pending FDA Approval

Emery L Chen, MD

Endocrine Surgeon, Woodland Clinic, Woodland, CaliforniaThyroid Cancer

Venkata Sri Cherukumilli, MD

Pediatric Resident, University of California–San Diego School ofMedicine, La Jolla, California

Rheumatoid Arthritis

Meera Chitlur, MD

Associate Professor of Pediatrics, Division of Hematology/

Oncology, Children’s Hospital of Michigan, Detroit, MichiganHemophilia and Related Bleeding Disorders

Nonimmune Hemolytic Anemia

John F Coyle, II, MD

Clinical Professor, Department of Medicine, University ofOklahoma College of Medicine–Tulsa, Tulsa, OklahomaDisturbances Caused by Heat

vii

Lester M Crawford, PhD

Formerly Research Professor, Georgetown University School of

Medicine, Washington, DC; Head, Department of Physiology,

University of Georgia College of Medicine, Athens, Georgia

Foodborne Illness

Burke A Cunha, MD

Professor of Medicine, Stony Brook University Medical Center

School of Medicine, Stony Brook, New York; Chief, Infectious

Disease Division, Winthrop–University Hospital, Mineola,

New York

Bacterial Infection of the Urinary Tract In Women; Viral and

Mycoplasmal Pneumonias

F William Danby, MD, FRCPC

Adjunct Assistant Professor of Surgery (Dermatology), Dartmouth

Medical School, Hanover, New Hampshire

Anogenital Pruritus

Ralph C Daniel, MD

Department of Dermatology, St Dominic-Jackson Memorial

Hospital, Jackson, Mississippi

Diseases of the Nails

Athena Daniolos, MD

Associate Professor, Department of Dermatology, University of

Wisconsin School of Medicine and Public Health; Attending

Physician, University Health Services, University of Wisconsin,

Madison, Wisconsin

Condyloma Accuminata (Genital Warts)

Stella Dantas, MD

Physician, Department of Obstetrics and Gynecology, Beaverton

Medical Office, Northwest Permanente PC Physicians and

Surgeons, Beaverton, Oregon

Uterine Leiomyomas

Andre Dascal, MD, FRCPC

Associate Professor, Departments of Medicine, Microbiology, and

Immunology, McGill University Faculty of Medicine; Senior

Infectious Disease Physician, Sir Mortimer B Davis-Jewish

General Hospital, Montreal, Quebec, Canada

Acute Infectious Diarrhea

Susan Davids, MD, MPH

Associate Professor of Medicine, Medical College of Wisconsin;

Associate Program Director, Internal Medicine Residency,

Clement J Zablocki Veterans Affairs Medical Center,

Milwaukee, Wisconsin

Acute Bronchitis

Susan A Davidson, MD

Associate Professor, University of Colorado–Denver School of

Medicine; Chief, Gynecologic Oncology, University of

Colorado Hospital, Aurora, Colorado

Neoplasms of the Vulva

Melinda V Davis-Malesevich, MD

Resident, Bobby R Alford Department of Otolaryngology – Head

& Neck Surgery, Baylor College of Medicine, Houston, Texas

Obstructive Sleep Apnea

Francisco J.A de Paula, MD, PhD

Assistant Professor, Department of Internal Medicine, School of

Medicine of Ribeirao Preto, USP, Ribeirao Preto, Brazil

Osteoporosis

Prakash C Deedwania, MD

Professor of Medicine, University of California–San FranciscoSchool of Medicine, San Francisco, California; Chief,Cardiology Section, Veterans Affairs Central California HealthCare System, Fresno, California

Premature Beats

Phyllis A Dennery, MD

Professor of Pediatrics, University of Pennsylvania School ofMedicine; Werner and Gertrude Henle Chair and Chief,Division of Neonatology, Children’s Hospital of Philadelphia,Philadelphia, Pennsylvania

Hemolytic Disease of the Fetus and Newborn

Stephen R Deputy, MD

Assistant Professor of Neurology, Louisiana State UniversitySchool of Medicine; Staff Neurologist, Children’s Hospital,New Orleans, Louisiana

Traumatic Brain Injury in Children

Richard D deShazo, MD

Professor of Medicine and Pediatrics and Billy S GuytonDistinguished Professor, University of Mississippi College ofMedicine; Chair, Department of Medicine, University ofMississippi Medical Center, Jackson, MississippiPneumoconiosis

Clio Dessinioti, MD, MSc

Attending Dermatologist, Andreas Sygros Hospital, Athens,Greece

Parasitic Diseases of the Skin

Gretchen M Dickson, MD, MBA

Assistant Professor, Department of Family and CommunityMedicine, University of Kansas School of Medicine–Wichita,Wichita, Kansas

Otitis Media

Douglas DiOrio, MD

Adjunct Clinical Professor, The Ohio State University College ofMedicine; Fellowship Director, Riverside Sports Medicine,Riverside Methodist Hospital, Columbus, Ohio

Common Sports Injuries

Sunil Dogra, MD, DNB, MNAMS

Associate Professor, Department of Dermatology, Venereology &Leprology, Postgraduate Institute of Medical Education &Research, Chandigarh, India

Leprosy

Basak Dokuzoguz, MD

Chief, Infectious Diseases and Clinical Microbiology Clinic,Ankara Numune Education and Research Hospital, Ankara,Turkey

Brucellosis

Joseph Domachowske, MD

Professor of Pediatrics, Microbiology, and Immunology, StateUniversity of New York Upstate Medical University, Syracuse,New York

Infectious Mononucleosis

Geoffrey A Donnan, MD

Department of Neurology, University of Melbourne Faculty ofMedicine, Dentistry, and Health Sciences; Florey NeuroscienceInstitutes, Carlton South, Victoria, Australia

Ischemic Cerebrovascular Disease

viii

Craig L Donnelly, MD

Dartmouth Medical School, Hanover, New Hampshire; Chief,

Child and Adolescent Psychiatry, Dartmouth-Hitchcock

Medical Center, Lebanon, New Hampshire

Attention Deficit/Hyperactivity Disorder

John Dorsch, MD

Associate Professor, Family and Community Medicine, University

of Kansas School of Medicine–Wichita, Wichita, Kansas

The Red Eye

Douglas A Drevets, MD, DTM&H

Professor and Chief, Section of Infectious Diseases, University of

Oklahoma Health Sciences Center; Staff Physician, Veterans

Affairs Medical Center, Oklahoma City, Oklahoma

Plague

Jean Dudler, MD

Me´decin-chef, Service de Rhumatologie, HFR Fribourg–Hoˆpital

Cantonal, Fribourg, Switzerland; Privat Docent, Division of

Rheumatology, University of Lausanne, Lausanne,

Switzerland

Rat-Bite Fever

Peter R Duggan, MD

Associate Clinical Professor of Medicine, University of Calgary,

Calgary, Alberta, Canada

Polycythemia Vera

Kim Eagle, MD

Albion Walter Hewlett Professor of Internal Medicine, Chief of

Clinical Cardiology, and Director, Cardiovascular Center,

University of Michigan Health System, Ann Arbor, Michigan

Julian Elliott, MB, BS, FACP

Conjoint Senior Lecturer, National Centre in HIV Epidemiology

and Clinical Research, University of New South Wales,

Sydney; Infectious Diseases Physician, Alfred Hospital,

Melbourne; HIV Clinical Advisor, International Health

Research Group, Macfarlane Burnet Institute for Medical

Research and Public Health, Melbourne, New South Wales,

Australia

Psittacosis

Sean P Elliott, MD, MS

Associate Professor of Urology and Director of Urologic

Reconstruction, University of Minnesota School of Medicine,

Associate Professor of Internal Medicine (Section of Infectious

Diseases) and Medical Microbiology, University of Manitoba,

Winnipeg, Manitoba, Canada

Blastomycosis

Tobias Engel, MD

Pediatric and Reproductive Endocrinology Branch, NationalInstitute of Child Health and Human Development, NationalInstitutes of Health, Bethesda, Maryland

Pheochromocytoma

Scott K Epstein, MD

Dean for Educational Affairs and Professor of Medicine, TuftsUniversity School of Medicine, Boston, MassachusettsAcute Respiratory Failure

Andrew M Evens, DO, MSc

Associate Professor of Medicine; Deputy Director for Clinical andTranslational Research and CRO Medical Director, UMassMemorial Cancer Center, Division of Hematology/Oncology;

Director, Lymphoma Program, The University of MassachusettsMedical School, Worcester, Massachusetts

Non-Hodgkin’s Lymphoma

Walid A Farhat, MD

Associate Professor, Department of Surgery and PediatricUrologist, The Hospital for Sick Children, Toronto, Ontario,Canada

Childhood Incontinence

Dorianne Feldman, MD, MSPT

Instructor of Physical Medicine and Rehabilitation, The JohnsHopkins University School of Medicine, Baltimore, MarylandRehabilitation of the Stroke Patient

Polymyalgia Rheumatica and Giant Cell Arteritis

Terry D Fife, MD

Associate Professor of Clinical Neurology, University of Arizona;

Director, Arizona Balance Center, Barrow NeurologicalInstitute, Phoenix, Arizona

Alan B Fleischer, Jr., MD

Professor and Chair, Department of Dermatology, Wake Forest

University School of Medicine, Winston-Salem, North Carolina

Acne Vulgaris and Rosacea

Raja Flores, MD

Professor and Chief, Division of Thoracic Surgery, Mount Sinai

Medical Center, New York, New York

Pleural Effusions and Empyema Thoracis

Brian J Flynn, MD

Associate Professor of Urology, University of Colorado–Denver

School of Medicine, Aurora, Colorado

Urethral Strictures

Nathan B Fountain, MD

Professor of Neurology and Director, Dreifuss Comprehensive

Epilepsy Program, University of Virginia, Charlottesville,

Clinical Associate Professor, Department of Family and

Community Medicine, University of Kansas School of

Medicine–Wichita, Wichita, Kansas; Program Director, Smoky

Hill Family Medicine Residency Program, Salina, Kansas

Nongonococcal Urethritis

Ellen W Freeman, PhD

Research Professor, Departments of Obstetrics/Gynecology and

Psychiatry, University of Pennsylvania School of Medicine,

Philadelphia, Pennsylvania

Premenstrual Syndrome

Theodore M Freeman, MD

San Antonio Asthma and Allergy Clinic, San Antonio, Texas

Allergic Reaction to Stinging Insects

Aaron Friedman, MD

Ruben Bentson Professor and Chair, Pediatrics, University of

Minnesota, Minneapolis, Minnesota

Parenteral Fluid Therapy in Children

R Michael Gallagher, DO

Director, Headache Center of Central Florida, Melbourne, Florida

Headache

John Garber, MD

Instructor in Medicine, Harvard Medical School; Fellow in

Gastroenterology, Massachusetts General Hospital, Boston,

Massachusetts

Acute and Chronic Viral Hepatitis

Khalil G Ghanem, MD, PhD

Associate Professor of Medicine, The Johns Hopkins University

School of Medicine, Baltimore, Maryland

Gonorrhea

Donald L Gilbert, MD, MS

Professor of Pediatrics and Neurology, Cincinnati Children’s

Hospital Medical Center and University of Cincinnati,

Mark T Gladwin, MD

Professor of Medicine, University of Pittsburgh School ofMedicine; Chief; Division of Pulmonary, Allergy and CriticalCare Medicine, University of Pittsburgh, Pittsburgh,

PennsylvaniaSickle Cell Disease

Robert Goldstein, MD

Director of Cardiac Device Clinic, Assistant Professor ofMedicine, Division of Cardiology, Case Medical Center,Cleveland, Ohio

E Ann Gormley, MD

Professor of Surgery (Urology), Dartmouth Medical School,Hanover, New Hampshire; Staff Urologist, Dartmouth-Hitchcock Medical Center, Lebanon, New HampshireUrinary Incontinence

Eduardo Gotuzzo, MD

Principal Professor of Medicine, Universidad Peruana CayetanoHeredia; Chief, Department of Infectious, Tropical, andDermatologic Diseases, Hospital National Cayetano Heredia,Lima, Peru

Melanocytic Nevi

x

Professor of Pediatrics, Stony Brook University Medical Center

School of Medicine, Stony Brook, New York; Medical Director

and Associate Chair, Department of Pediatrics, Long Island

Regional Poison and Drug Information Center,

Winthrop-University Hospital, Mineola, New York

Medical Toxicology: Ingestions, Inhalations, and Dermal and Ocular

Absorptions

David Gregory, MD

Assistant Clinical Professor of Family Medicine, University of

Virginia School of Medicine, Charlottesville, Virginia; Assistant

Clinical Professor of Family Medicine, Virginia Commonwealth

University School of Medicine, Richmond, Virginia; Director of

Didactic Curriculum, Lynchburg Family Medicine Residency;

Staff Physician in Family Medicine and Obstetrics, Lynchburg

General Hospital and Virginia Baptist Hospital, Lynchburg,

Virginia

Resuscitation of the Newborn

Priya Grewal, MD

Assistant Professor, Division of Liver Diseases, Mount Sinai

School of Medicine, New York, New York

Cirrhosis

Charles Grose, MD

Professor of Pediatrics, University of Iowa Carver College of

Medicine; Director of Infectious Diseases Division, Children’s

Hospital of Iowa, Iowa City, Iowa

Varicella (Chickenpox)

Robert Grossberg, MD

Assistant Professor of Medicine, Infectious Diseases, Albert

Einstein College of Medicine, Bronx, New York

Fungal Diseases of the Skin

Michael Groves, MD

Resident, Bobby R Alford Department of Otolaryngology–Head

& Neck Surgery, Baylor College of Medicine, Houston, Texas

Nonallergic Perennial Rhinitis

Eva C Guinan, MD

Associate Professor of Pediatrics and Director, Linkages Program,

Harvard Catalyst, Harvard Medical School, Boston,

Massachusetts

Aplastic Anemia

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

Juliet Gunkel, MD

Assistant Professor, University of Wisconsin School of Medicine

and Public Health; Staff Physician, University of Wisconsin

Hospitals and Clinics and Meriter Hospital, Madison,

Ronald Hall, II, PharmD

Associate Professor, Texas Tech University Health Sciences CenterSchool of Pharmacy, Dallas, Texas

Tuberculosis and Other Mycobacterial Diseases

Nicola A Hanania, MD, MS

Associate Professor of Medicine, Section of Pulmonary, CriticalCare, and Sleep Medicine; Director, Asthma Clinical ResearchCenter, Baylor College of Medicine, Houston, Texas

Chronic Obstructive Pulmonary Disease

Associate Professor, Department of Family Medicine, University

of Nebraska Medical Center, Omaha, NebraskaDysmenorrhea

George D Harris, MD, MS

Professor and Dean, Year 1 and 2 Medicine, University ofMissouri–Kansas City School of Medicine; Faculty, FamilyMedicine Residency Program at Truman Medical Center–

Lakewood, Kansas City, MissouriOsteomyelitis

Emily J Herndon, MD

Assistant Professor, Department of Family and PreventiveMedicine, Emory University School of Medicine; StaffPhysician, Department of Community Medicine, Grady HealthSystem, Atlanta, Georgia

Contraception

David G Hill, MD

Assistant Clinical Professor, Yale University School of Medicine,New Haven, Connecticut; Waterbury Pulmonary Associates,Waterbury, Connecticut

President and CEO, New York Blood Center; Professor, Division

of Hematology, Department of Medicine, Weill Cornell MedicalCollege, New York, New York

Adverse Effects of Blood Transfusion

xi

Stacey Hinderliter, MD

Clinical Assistant Professor of Family Medicine, University of

Virginia School of Medicine, Charlottesville, Virginia; Clinical

Assistant Professor of Family Medicine, Virginia

Commonwealth University School of Medicine, Richmond,

Virginia; Pediatric Faculty, Lynchburg Family Medicine

Residency; Staff Physician, Lynchburg General Hospital,

Lynchburg, Virginia

Resuscitation of the Newborn

Molly Hinshaw, MD

Assistant Professor of Dermatology, University of Wisconsin

School of Medicine and Public Health, Madison, Wisconsin;

Dermatopathologist, Dermpath Diagnostics, Brookfield,

Professor of Internal Medicine and Pharmacology, University of

Iowa Carver College of Medicine, Iowa City, Iowa

Thalassemia

Sarah A Holstein, MD, PhD

Assistant Professor, Department of Internal Medicine, University

of Iowa Carver College of Medicine, Iowa City, Iowa

Thalassemia

Marisa Holubar, MD

Clinical Teaching Fellow, Warren Alpert Medical School of Brown

University, Providence, Rhode Island

Severe Sepsis and Septic Shock

M Ekramul Hoque, MBBS, MPH (Hons), PhD

Lecturer in Community Health, School of Medicine, Deakin

University, Geelong, Victoria, Australia

Giardiasis

Ahmad Reza Hossani-Madani, MD

Department of Dermatology, Howard University College of

Scientist, Institute of Immunology, Laboratoire National de Sante´/

Centre de Recherche Public-Sante´, Luxembourg

Rubella and Congenital Rubella

Christine Hudak, MD

Summa Health System, Akron, Ohio

Vulvovaginitis

William J Hueston, MD

Professor and Chair, Department of Family Medicine, Medical

University of South Carolina, Charleston, South Carolina

Hyperthyroidism; Hypothyroidism

Joseph M Hughes, MD

Associate Professor of Clinical Medicine, Columbia UniversityCollege of Physicians and Surgeons, New York, New York;Attending Physician, Department of Medicine, Division ofEndocrinology, Bassett Healthcare, Cooperstown, New YorkAdrenocortical Insufficiency

Scott A Hundahl, MD

Professor of Surgery, University of California–Davis School ofMedicine, Sacramento, California; Chief of Surgery, VeteransAffairs Northern California Health Care System, Mather,California

Tumors of the Stomach

Stephen P Hunger, MD

Professor of Pediatrics, University of Colorado–Denver School ofMedicine; Section Chief, Center for Cancer and Blood Disordersand Ergen Family Chair in Pediatric Cancer, The Children’sHospital, Aurora, Colorado

Acute Leukemia in Children

Alan C Jackson, MD, FRCPC

Professor of Medicine (Neurology) and Medical Microbiology,University of Manitoba Faculty of Medicine; Head, Section ofNeurology, Winnipeg Regional Health Authority, Winnipeg,Manitoba, Canada

Rabies

Danny O Jacobs, MD, MPH

David C Sabiston, Jr., Professor and Chair, Department ofSurgery, Duke University School of Medicine, Durham, NorthCarolina

Diverticula of the Alimentary Tract

Kurt M Jacobson, MD

Cardiovascular Medicine Consultant, Billings Clinic, Billings,Montana; Interventional Cardiovascular Fellow, University ofWisconsin Hospital and Clinics, Madison, WisconsinMitral Valve Prolapse

Robert M Jacobson, MD

Professor of Pediatrics, College of Medicine, Mayo Clinic; Chair,Department of Pediatric and Adolescent Medicine, MayoClinic, Rochester, Minnesota

Immunization Practices

James J James, MD, DrPH, MHA

Director, Center for Public Health Preparedness and DisasterResponse; Editor-in-Chief, Journal of Disaster Medicine andPublic Health Preparedness, American Medical Association,Chicago, Illinois

Biologic Agents Reference Chart: Symptoms, Tests, and Treatment; ToxicChemical Agents Reference Chart: Symptoms and Treatment

xii

Children’s Medical Research Institute/Arthritis Foundation

Oklahoma Chapter Endowed Chair, Professor of Pediatrics and

Section Chief, Pediatric Rheumatology, University of Oklahoma

College of Medicine, Oklahoma City, Oklahoma

Juvenile Idiopathic Arthritis

Nathaniel Jellinek, MD

Department of Dermatology, Warren Alpert Medical School of

Brown University, Providence, Rhode Island

Diseases of the Nails

Roy M John, MD, PhD

Clinical Assistant Professor, Harvard Medical School; Associate

Director, Cardiac Electrophysiology Laboratory, Brigham and

Women’s Hospital, Boston, Massachusetts

Cardiac Arrest: Sudden Cardiac Death

James F Jones, MD

Research Medical Officer, Chronic Viral Diseases Branch, National

Center for Zoonotic, Vector-Borne, and Enteric Diseases, Centers

for Disease Control and Prevention, Atlanta, Georgia

Chronic Fatigue Syndrome

Marc A Judson, MD

Professor of Medicine, Medical University of South Carolina,

Charleston, South Carolina

Sarcoidosis

Tamilarasu Kadhiravan, MD

Assistant Professor of Medicine, Department of Medicine,

Jawaharlal Institute of Postgraduate Medical Education and

Research–Puducherry, Puducherry, India

Typhoid Fever

Harmit Kalia, DO

Division of Gastroenterology, University of Medicine and

Dentistry-New Jersey Medical School, Newark, New Jersey

Cirrhosis

Walter Kao, MD

Associate Professor of Medicine, University of Wisconsin School

of Medicine and Public Health; Attending Cardiologist, Heart

Failure and Transplant Program, University of Wisconsin

Hospitals and Clinics, Madison, Wisconsin

Professor of Dermatology, Department of Dermatology,

University of Athens School of Medicine; Andreas Sygzos

Hospital, Athens, Greece

Parasitic Diseases of the Skin

Philip O Katz, MD

Clinical Professor of Medicine, Jefferson Medical College of

Thomas Jefferson University; Chairman, Division of

Gastroenterology, Albert Einstein Medical Center, Philadelphia,

Pennsylvania

Dysphagia and Esophageal Obstruction

Arthur Kavanaugh, MD

Professor of Medicine, University of California–San Diego, School

of Medicine, La Jolla, CaliforniaRheumatoid Arthritis

Clive Kearon, MRCPI, FRCPC, PhD

Professor of Medicine, McMaster University Faculty of HealthSciences; Attending Physician, Henderson General Hospital,Hamilton, Ontario, Canada

Venous Thromboembolism

B Mark Keegan, MD, FRCPC

Associate Professor and Section Chair, Multiple Sclerosis andAutoimmune Neurology, Department of Neurology, MayoClinic, Rochester, Minnesota

Anaphylaxis and Serum Sickness

Hematology-Thrombotic Thrombocytopenic Purpura

Joel D Klein, MD, FAAP

Professor of Pediatrics, Jefferson Medical College of ThomasJefferson University, Philadelphia, Pennsylvania; Division ofPediatric Infectious Diseases, Alfred I duPont Hospital forChildren, Wilmington, Delaware

Gerald B Kolski, MD, PhD

Clinical Professor of Pediatrics, Temple University School of

Medicine; Adjunct Clinical Professor of Pediatrics, Drexel

University College of Medicine, Philadelphia, Pennsylvania;

Attending Physician, Crozer Chester Medical Center, Upland,

Pennsylvania

Asthma in Children

Frederick K Korley, MD

Robert E Meyerhoff Assistant Professor of Emergency Medicine,

Johns Hopkins University School of Medicine; Staff, The Johns

Hopkins Medicine Institutions, Baltimore, Maryland

Disturbances Caused by Cold

Kristin Kozakowski, MD

Pediatric Urology Senior Fellow, The Hospital for Sick Children,

Toronto, Ontario, Canada

Childhood Incontinence

Robert A Kratzke, MD

John Skoglund Chair of Lung Cancer Research, University of

Minnesota Medical School; Associate Professor, University of

Minnesota Medical Center, Minneapolis, Minnesota

Primary Lung Cancer

Jeffrey A Kraut, MD

Professor of Medicine, David Geffen School of Medicine at UCLA;

Chief of Dialysis, Veterans Affairs Greater Los Angeles

Healthcare System, Los Angeles, California

Chronic Renal Failure

Jacques Kremer, PhD

Postdoctoral Program, Institute of Immunology, National

Laboratory of Health, Luxembourg

Measles (Rubeola)

John N Krieger, MD

Professor of Urology, University of Washington School of

Medicine; Chief of Urology, Veterans Affairs Puget Sound

Health Care System, Seattle, Washington

Bacterial Infections of the Male Urinary Tract

Leonard R Krilov, MD

Chief, Pediatric Infectious Diseases and International Adoption,

Winthrop University Hospital, Pediatric Specialty Center,

Mineola, New York

Travel Medicine

Lakshmanan Krishnamurti, MD

Department of Medicine, Vascular Medicine Institute, University

of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Sickle Cell Disease

Roshni Kulkarni, MD

Professor, Department of Pediatrics and Human Development,

Michigan State University College of Medicine, East Lansing,

Michigan

Hemophilia and Related Bleeding Disorders

Bhushan Kumar, MD, MNAMS, FRCP (Edin), FRCP

(London)

Former Professor and Head, Department of Dermatology,

Venerology & Leprology, Postgraduate Institute of Medical

Education & Research, Chandigarh, India

Leprosy

Seema Kumar, MD

Assistant Professor of Pediatrics, Mayo Clinic College ofMedicine; Consultant, Division of Pediatrics, Endocrinology,and Metabolism, Department of Pediatrics, Mayo Clinic,Rochester, Minnesota

Severe Sepsis and Septic Shock

Andrew B Lassman, MD

Department of Neurology and Brain Tumor Center, MemorialSloan-Kettering Cancer Center, New York, New YorkBrain Tumors

Barbara A Latenser, MD

Clara L Smith Professor of Burn Treatment, Department ofSurgery, University of Iowa Carver College of Medicine;Medical Director, Burn Treatment Center, University of IowaHospitals and Clinics, Iowa City, Iowa

Burn Treatment Guidelines

Christine L Lau, MD

Assistant Professor of Surgery, Division of Thoracic andCardiovascular Surgery, University of Virginia School ofMedicine, Charlottesville, Virginia

Pericarditis and Pericardial Effusions

xiv

Paul J Lee, MD

Winthrop University Hospital, Pediatric Specialty Center,

Mineola, New York

Travel Medicine

Jerrold B Leikin, MD

Professor of Emergency Medicine, Northwestern University

Feinberg School of Medicine, Chicago, Illinois; Professor of

Medicine, Rush Medical College, Chicago, Illinois; Director of

Medical Toxicology, Evanston Northwestern

Healthcare-Omega, Glenbrook Hospital, Glenview, Illinois

Disturbances Caused by Cold

Assistant Professor, Ophthalmology, Baylor College of Medicine;

Staff Physician, Eye Care Line, Michael E DeBakey VA Medical

Center, Houston, Texas

Glaucoma

Morten Lindbaek, MD

Professor of General Practice, University of Oslo, Oslo, Norway

Sinusitis

Janet C Lindemann, MD, MBA

Professor of Family Medicine and Dean of Medical Student

Education, Sanford School of Medicine, University of South

Dakota, Sioux Falls, South Dakota

Fatigue

Jeffrey A Linder, MD, MPH, FACP

Assistant Professor of Medicine, Harvard Medical School;

Associate Physician, Division of General Medicine and Primary

Care, Brigham and Women’s Hospital, Boston, Massachusetts

Influenza

Gary H Lipscomb, MD

Professor and Director, Division of General Obstetrics and

Gynecology, Department of Obstetrics and Gynecology,

Northwestern University Feinberg School of Medicine,

Chicago, Illinois

Ectopic Pregnancy

James A Litch, MD, DTMH

Clinical Assistant Professor, University of Washington School of

Medicine and School of Public Health and Community

Medicine, Seattle, Washington

High-Altitude Illness

James Lock, MD

Professor of Child Psychiatry and Pediatrics, Stanford University

School of Medicine; Medical Director, Eating Disorder

Program, Lucile Packard Children’s Hospital, Stanford,

California

Bulimia Nervosa

Robert C Lowe, MD

Associate Professor of Medicine, Boston University School of

Medicine, Boston, Massachusetts

Gastritis and Peptic Ulcer Disease

Benjamin J Luft, MD

Edmund D Pellegrino Professor of Medicine, Stony Brook

University Medical Center School of Medicine, Stony Brook,

James M Lyznicki, MS, MPH

Associate Director, Center for Public Health Preparedness andDisaster Response, American Medical Association, Chicago,Illinois

Biologic Agents Reference Chart: Symptoms, Tests, and Treatment; ToxicChemical Agents Reference Chart: Symptoms and Treatment

Diverticula of the Alimentary Tract

Woraphong Manuskiatti, MD

Professor of Dermatology, Department of Dermatology, Faculty ofMedicine, Siriraj Hospital, Mahidol University, Bangkok,Thailand

Keloids

Lynne Margesson, MD, FRCPC

Adjunct Assistant Professor of Surgery (Dermatology) andObstetrics and Gynecology, Dartmouth Medical School,Hanover, New Hampshire

Anogenital Pruritus

Paul Martin, MD

Chief, Division of Hepatology, Schiff Liver Institute/Center forLiver Diseases, University of Miami Miller School of Medicine,Miami, Florida

Normal Infant Feeding

xv

Pinckney J Maxwell, IV, MD

Assistant Professor of Surgery, Division of Colon and Rectal

Surgery, Jefferson Medical College of Thomas Jefferson

University, Philadelphia, Pennsylvania

Tumors of the Colon and Rectum

Ali Mazloom, MD

University of Texas School of Public Health, Houston, Texas

Hodgkin’s Disease: Radiation Therapy

Anthony L McCall, MD, PhD

James M Moss Professor of Diabetes, University of Virginia

School of Medicine; Endocrinologist, University of Virginia

Health Care System, Charlottesville, Virginia

Diabetes Mellitus in Adults

Jill D McCarley, MD

Assistant Professor of Psychiatry, Quillen College of Medicine,

East Tennessee State University, Johnson City, Tennessee

Mood Disorders: Depression and Mood Instability

Laura J McCloskey, PhD

Assistant Professor of Pathology, Anatomy, and Cell Biology,

Jefferson Medical College of Thomas Jefferson University;

Associate Director, Clinical Laboratories, Thomas Jefferson

University Hospitals, Philadelphia, Pennsylvania

Reference Intervals for the Interpretation of Laboratory Tests

Michael McGuigan, MD

Medical Director, Long Island Regional Poison and Drug

Information Center, Winthrop-University Hospital, Mineola,

New York

Medical Toxicology: Ingestions, Inhalations, and Dermal and Ocular

Absorptions

Donald McNeil, MD

Associate Professor of Clinical Medicine, Department of

Immunology, The Ohio State University College of Medicine

and Public Health, Columbus, Ohio

Allergic Reactions to Drugs

Professor, Department of Neurology and Department of

Psychiatric and Biobehavioral Sciences, David Geffen School of

Medicine at UCLA; Attending Physician, Neurobehavior Unit,

Veterans Affairs Greater Los Angeles Healthcare System, Los

Angeles, California

Alzheimer’s Disease

Moises Mercado, MD

Professor of Medicine, Faculty of Medicine, Universidad Nacional

Autonoma de Mexico; Head, Endocrine Service, and

Experimental Endocrinology Unit, Hospital de Especialidades,

Centro Medico Nacional Siglo XXI, Institute Mexicano del

Segero Social, Mexico City, Mexico

Acromegaly

Jeffrey Wm Milks, MD

Director, Geriatric Fellowship, Riverside Methodist Hospital;

Medical Director, Senior Independence Hospice–Ohio, Ohio

Presbyterian Retirement Services, Columbus, Ohio

Disseminated Intravascular Coagulation

Timothy I Morgenthaler, MD

Associate Professor of Medicine, Pulmonary and Critical CareMedicine, Center for Sleep Medicine, Mayo Clinic andFoundation, Rochester, Minnesota

Sleep Disorders

Warwick L Morison, MD

Professor of Dermatology, The Johns Hopkins University School

of Medicine, Baltimore, MarylandSunburn

Psychocutaneous Medicine

Judd W Moul, MD

Professor and Chief, Division of Urology; Director, Duke ProstateCenter, Department of Surgery, Duke University MedicalCenter, Durham, North Carolina

Benign Prostatic Hyperplasia

Melanocytic Nevi

xvi

Diya F Mutasim, MD

Chair, Department of Dermatology and Professor of Dermatology

and Pathology, University of Cincinnati College of Medicine,

Cincinnati, Ohio

Bullous Diseases

Nicole Nader, MD

Instructor, Mayo Clinic College of Medicine; Fellow, Division of

Pediatric Endocrinology and Metabolism, Department of

Pediatrics, Mayo Clinic, Rochester, Minnesota

Obesity

Alykhan S Nagji, MD

Resident, Department of Surgery, University of Virginia School of

Medicine, Charlottesville, Virginia

Atelectasis

Tara J Neil, MD

Clinical Assistant Professor, Department of Family and

Community Medicine, University of Kansas School of

Medicine–Wichita; Associate Director, Via Christi Family

Medicine Residency Program, Wichita, Kansas

Postpartum Care

David G Neschis, MD

Clinical Associate Professor of Surgery, University of Maryland

School of Medicine, Baltimore, Maryland; Vascular Surgeon,

The Maryland Vascular Center, Glen Burnie, Maryland

Acquired Diseases of the Aorta

David H Neustadt, MD

Clinical Professor of Medicine, University of Louisville School of

Medicine; Senior Attending, University Hospital, Jewish

Hospital, Louisville, Kentucky

Osteoarthritis

Douglas E Ney, MD

Assistant Professor, University of Colorado–Denver School of

Medicine; Attending Physician, University of Colorado

Hospital, Aurora, Colorado

Brain Tumors

Lucybeth Nieves-Arriba, MD

Case Western Reserve University School of Medicine; Gynecologic

Oncology, Women’s Health Institute, Cleveland Clinic,

Cleveland, Ohio

Cervical Cancer

Enrico M Novelli, MD

Department of Medicine, Vascular Medicine Institute, University

of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Sickle Cell Disease

Jeffrey P Okeson, DMD

Professor and Chair, Oral Health Science; Director, Orofacial Pain

Program, College of Dentistry, University of Kentucky,

Lexington, Kentucky

Temporomandibular Disorders

David L Olive, MD

Professor of Obstetrics and Gynecology, University of Wisconsin

School of Medicine and Public Health, Madison, Wisconsin

Endometriosis

Peck Y Ong, MD

Assistant Professor of Clinical Pediatrics, Department of

Pediatrics, Keck School of Medicine of the University of

Southern California; Attending Physician, Division of Clinical

Immunology and Allergy, Children’s Hospital Los Angeles, Los

Pheochromocytoma

Richard L Page, MD

George R and Elaine Love Professor and Chair, Department ofMedicine, University of Wisconsin School of Medicine andPublic Health, Madison, Wisconsin

Pratik Pandharipande, MD, MSCI

Anesthesiology Service, Veterans Administration Tennessee ValleyHealthcare Systems; Associate Professor of Anesthesiology/

Critical Care, Vanderbilt University Medical Center, Nashville,Tennessee

Paul Paulman, MD

Assistant Dean for Clinical Skills and Quality, Family Medicine,

University of Nebraska College of Medicine, Omaha, Nebraska

Iron Deficiency

Alexander Perez, MD

Assistant Professor of Surgery, Duke University School of

Medicine, Durham, North Carolina

Diverticula of the Alimentary Tract

Allen Perkins, MD, MPH

Professor and Chairman, Department of Family Medicine,

University of South Alabama College of Medicine, Mobile,

Alabama

Marine Poisonings, Envenomations, and Trauma

William A Petri, Jr., MD, PhD

Chief, Division of Infectious Disease and International Health,

University of Virginia Medical Center, Charlottesville, Virginia

Amebiasis

Vesna Petronic-Rosic, MD, MSc

Associate Professor and Clinic Director, University of Chicago

Section of Dermatology, Chicago, Illinois

Melanoma

Michael E Pichichero, MD

Director of Research, Department of Immunology and Center for

Infectious Disease, Rochester General Hospital Research

Institute, Rochester, New York

Whooping Cough (Pertussis)

Claus A Pierach, MD

Professor of Medicine, University of Minnesota Medical School,

Abbott Northwestern Hospital, Minneapolis, Minnesota

Porphyrias

Antonello Pietrangelo, MD, PhD

Professor of Internal Medicine, Department of Internal Medicine,

University of Modena and Reggio Emilia, Modena, Italy

Hemochromatosis

Daniel K Podolsky, MD

Professor of Internal Medicine, University of Texas Southwestern

Medical School; Philip O’Bryan Montgomery Jr., MD,

Distinguished Presidential Chair in Academic Administration

and Doris and Bryan Wildenthal Distinguished Chair in

Medical Science, University of Texas Southwestern Medical

Center, Dallas, Texas

Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative Colitis

Michael A Posencheg, MD

Medical Director, Newborn Nursery; Associate Medical Director,

Intensive Care Nursery; Assistant Professor of Clinical

Pediatrics, Division of Neonatology and Newborn Services,

Hospital of the University of Pennsylvania, Philadelphia,

Pennsylvania

Hemolytic Disease of the Fetus and Newborn

Manuel Praga, MD

Associate Professor of Medicine, Universidad Complutense; Head,

Nephrology Department, Hospital 12 de Octubre, Madrid,

Acute and Chronic Viral Hepatitis

Richard A Prinz, MD

Helen Shedd Keith Professor and Chair, Department of GeneralSurgery, Rush Medical College; Chair, Department of GeneralSurgery, Rush University Medical Center, Chicago, IllinoisThyroid Cancer

David Puchalsky, MD

Associate Professor of Dermatology, University of WisconsinSchool of Medicine and Public Health, Madison, WisconsinPapulosquamous Eruptions—Psoriasis

David M Quillen, MD

Associate Professor, Department of Community Health andFamily Medicine, University of Florida College of Medicine,Gainesville, Florida

Allergic Rhinitis Caused by Inhalant Factors; Epididymitis

Beth W Rackow, MD

Assistant Professor, Department of Obstetrics, Gynecology, andReproductive Sciences, Yale University School of Medicine,New Haven, Connecticut

Abnormal Uterine Bleeding

Peter S Rahko, MD

Professor of Medicine, University of Wisconsin School ofMedicine and Public Health; Director of Echocardiography,University of Wisconsin Hospitals and Clinics, Madison,Wisconsin

Mitral Valve Prolapse

S Vincent Rajkumar, MD

Professor of Medicine and Chair, Myeloma AmyloidosisDysproteinemia Group, Division of Hematology, Mayo Clinic,Rochester, Minnesota

Multiple Myeloma

Kirk D Ramin, MD

Associate Professor and Director, Maternal-Fetal MedicineFellowship Program, Department of Obstetrics andGynecology, University of Minnesota Medical School,Minneapolis, Minnesota

xviii

Elizabeth Reddy, MD

Fellow, Department of Medicine, Division of Infectious Disease,

Duke University, Durham, North Carolina

Professor of Medicine and Endocrinology, University of Auckland

Faculty of Medical and Health Sciences School of Medicine,

Auckland, New Zealand

Paget’s Disease of Bone

Robert L Reid, MD

Professor, Department of Obstetrics and Gynecology, Queen’s

University Faculty of Medicine; Chair, Division of Reproductive

Endocrinology and Infertility, Kingston General Hospital,

Kingston, Ontario, Canada

Amenorrhea

John D Reveille, MD

Professor of Internal Medicine and Director, Rheumatology and

Clinical Immunogenetics, The University of Texas Medical

School, Houston, Texas

Ankylosing Spondylitis

Robert W Rho, MD

Associate Professor of Medicine, Division of Cardiology,

University of Washington Medical Center, Seattle, Washington

Atrial Fibrillation

Jason R Roberts, MD

Gastrointestinal Fellow, Medical University of South Carolina,

Charleston, South Carolina

Gastroesophageal Reflux Disease

Malcolm K Robinson, MD

Assistant Professor of Surgery, Harvard Medical School;

Metabolic Support Service, Department of Surgery, Brigham

and Women’s Hospital, Boston, Massachusetts

Parenteral Nutrition in Adults

Nidra Rodriguez, MD

Assistant Professor of Pediatric Hematology, University of Texas

Medical School at Houston and University of Texas M D

Anderson Cancer Center, Houston Texas

Autoimmune Hemolytic Anemia

Giovanni Rosa, MD

University of Roma La Sapienza, Rome, Italy

Hiccups

Jonathan Rosand, MD, MSc

Director, Division of Neurocritical Care and Emergency

Neurology, Massachusetts General Hospital; Independent

Faculty, Center for Human Genetic Research, Massachusetts

General Hospital, Boston, Massachusetts

Intracerebral Hemorrhage

Peter G Rose, MD

Case Western Reserve University School of Medicine;

Section Head, Gynecologic Oncology, Women’s Health

Institute, Cleveland Clinic, Cleveland, Ohio

Cervical Cancer; Ovarian Cancer

Clifford J Rosen, MD

Professor of Medicine, Tufts University School of Medicine,Boston, Massachusetts; Senior Scientist, Maine Medical CenterResearch Institute, Maine Medical Center, Portland, MaineOsteoporosis

Richard N Rosenthal, MD

Arthur J Antenucci Professor of Clinical Psychiatry, ColumbiaUniversity College of Physicians and Surgeons; Chair,Department of Psychiatry, St Luke’s-Roosevelt Hospital Center,New York, New York

Alcoholism

Anne E Rosin, MD

Associate Professor of Dermatology, University of Wisconsin School

of Medicine and Public Health; Attending Physician, University

of Wisconsin Hospital and Clinics, Madison, WisconsinWarts (Verruca)

Spider Bites and Scorpion Stings

Susan L Samson, MD, PhD

Assistant Professor, Department of Medicine, Baylor College ofMedicine; Attending Physician, Ben Taub General Hospital,Houston, Texas

Hyponatremia

J Terry Saunders, PhD

Assistant Professor of Medical Education in Internal Medicine,University of Virginia School of Medicine, Charlottesville,Virginia

Diabetes Mellitus in Adults

Barry M Schaitkin, MD

Professor of Otolaryngology, University of Pittsburgh School ofMedicine; Residency Program Director, University of PittsburghMedical Center, Pittsburgh, Pennsylvania

Acute Peripheral Facial Paralysis (Bell’s Palsy)

Ralph M Schapira, MD

Professor and Vice Chair, Department of Medicine, MedicalCollege of Wisconsin; Staff Physician, Milwaukee VeteransAffairs Medical Center, Milwaukee, Wisconsin

Menopause

Lawrence R Schiller, MD

Clinical Professor of Internal Medicine, University of TexasSouthwestern Medical School; Attending Physician, DigestiveHealth Associates of Texas; Program Director,

Gastroenterology Fellowship, Baylor University MedicalCenter, Dallas, Texas

Malabsorption

xix

Janet A Schlechte, MD

Professor, Department of Internal Medicine, University of Iowa

Hospital, Iowa City, Iowa

Hyperprolactinemia

Kerrie Schoffer, MD, FRCPC

Assistant Professor in Neurology, Dalhousie University Faculty of

Medicine; Neurologist, QEII Health Sciences Centre, Halifax,

Nova Scotia, Canada

Peripheral Neuropathies

Kevin Schroeder, MD

Program Director, Transitional Year, and Medical Director of

Acute Dialysis, Riverside Methodist Hospital, Columbus, Ohio

Acute Renal Failure

Dan Schuller, MD

Professor of Medicine and Chief, Pulmonary-Critical Care and

Sleep Medicine Division, Creighton University, Omaha,

Nebraska

Primary Lung Abscess

Carlos Seas, MD

Associate Professor of Medicine, Universidad Peruana Cayetano

Jeredia; Chief, Inservice Department, Hospital National

Cayetano Heredia, Lima, Peru

Cholera

Steven A Seifert, MD, FAACT, FACMT

Professor, University of New Mexico School of Medicine; Medical

Director, New Mexico Poison Center, Albuquerque, New

Mexico

Venomous Snakebite

Edward Septimus, MD

Affiliated Professor, George Mason University School of Public

Policy, Fairfax, Virginia; Medical Director, Infection

Prevention, HCA Healthcare System, Nashville, Tennessee

Bacterial Pneumonia

Daniel J Sexton, MD

Professor of Medicine, Duke University School of Medicine,

Durham, North Carolina

Rickettsial and Ehrlichial Infections (Rocky Mountain Spotted Fever and

Typhus)

Beejal Shah, MD

Assistant Professor, Department of Medicine, Baylor College of

Medicine; Attending Physician, Ben Taub General Hospital,

Houston, Texas

Hyponatremia; Primary Aldosteronism

Jamile M Shammo, MD

Associate Professor of Medicine and Pathology, Division of

Hematology/Oncology, Rush University Medical Center,

Chicago, Illinois

Myelodysplastic Syndromes

Amir Sharafkhaneh, MD, PhD

Associate Professor of Medicine, Section of Pulmonary, Critical

Care, and Sleep Medicine; Director, Sleep Fellowship Program,

Baylor College of Medicine, Houston, Texas

Chronic Obstructive Pulmonary Disease

Ala I Sharara, MD

Professor of Medicine and Head, Division of Gastroenterology,American University of Beirut Medical Center; ConsultingProfessor, Duke University Medical Center, Durham, NorthCarolina

Bleeding Esophageal Varices

Michael J Smith, MD, MSCE

Assistant Professor, Department of Pediatrics, University

of Louisville School of Medicine; Attending Physician, Division

of Pediatric Infectious Diseases, Kosair Children’s Hospital,Louisville, Kentucky

Cat-Scratch Disease

Suman L Sood, MD

Assistant Professor of Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MichiganPlatelet-Mediated Bleeding Disorders

Panic Disorder

Todd Stephens, MD

Clinical Instructor, Family and Community Medicine, University

of Kansas School of Medicine–Wichita; Associate Director, ViaChristi Family Medicine Residency Program, Wichita, KansasGenital Ulcer Disease: Chancroid, Granuloma Inguinale, and Lympho-granuloma

Dennis L Stevens, MD, PhD

Professor of Medicine, University of Washington School ofMedicine, Seattle, Washington; Chief, Infectious Diseases,Veterans Affairs Medical Center, Boise, Idaho

Bacterial Diseases of the Skin

Brenda Stokes, MD

Assistant Clinical Professor of Family Medicine, InstructionalFaculty, University of Virginia School of Medicine,Charlottesville, Virginia; Assistant Clinical Professor,Department of Family Medicine, Virginia CommonwealthUniversity School of Medicine, Richmond, Virginia; MedicalStaff, Central Health-Lynchburg General and Virginia BaptistHospitals, Lynchburg, Virginia

Hypertensive Disorders of Pregnancy

xx

Constantine A Stratakis, MD, PhD

Program Head, Program on Developmental Endocrinology

and Genetics and Director, Pediatric Endocrinology

Training Program, National Institutes of Health, Bethesda,

Maryland

Cushing’s Syndrome

Harris Strokoff, MD

Child and Adolescent Psychiatrist, Northwestern Counseling and

Support Services, Saint Albans, Vermont

Attention Deficit/Hyperactivity Disorder

Prabhakar P Swaroop, MD

Assistant Professor of Internal Medicine, University of Texas

Southwestern Medical Center at Dallas, Dallas, Texas

Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative Colitis

Jessica P Swartout, MD

Fellow in Maternal-Fetal Medicine, Department of Obstetrics and

Gynecology, University of Minnesota Medical School,

Minneapolis, Minnesota

Antepartum Care

Masayoshi Takashima, MD

Director, The Sinus Center, and Director, Sleep Medicine

Fellowship–OTO Section, Bobby R Alford Department of

Otolaryngology–Head and Neck Surgery, Baylor College of

Medicine, Houston, Texas

Nonallergic Perennial Rhinitis; Obstructive Sleep Apnea

Matthew D Taylor, MD

Resident, Department of Surgery, University of Virginia Medical

Center, Charlottesville, Virginia

Atelectasis

Edmond Teng, MD, PhD

Assistant Professor, Department of Neurology, David Geffen

School of Medicine at UCLA; Neurobehavioral Unit and

Geriatric Research Education and Clinical Center, Veterans

Affairs Greater Los Angeles Healthcare System, Los Angeles,

California

Alzheimer’s Disease

Joyce M.C Teng, MD, PhD

Assistant Professor of Dermatology and Pediatrics, University of

Wisconsin School of Medicine and Public Health; Attending

Physician, University of Wisconsin Hospital and Clinics,

Professor of Medicine, Division of Geriatric Medicine, Saint Louis

University School of Medicine; Attending Physician, Saint Louis

University Hospital, St Louis, Missouri

Pressure Ulcers

Kenneth Tobin, DO

Clinical Assistant Professor and Director, Chest Pain Center,

University of Michigan Medical Center, Department of Internal

Medicine, Division of Cardiovascular Disease

Angina Pectoris

David E Trachtenbarg, MD

Medical Director, Methodist Diabetes Care Center; Clinical

Professor, Family and Community Medicine, University of

Illinois College of Medicine, Peoria, Illinois

Diabetic Ketoacidosis

Maria Trent, MD, MPH

Assistant Professor of Pediatrics, The Johns Hopkins UniversitySchool of Medicine; Active Staff, The Johns Hopkins HospitalChildren’s Center, Baltimore, Maryland

Pelvic Inflammatory Disease

Parenteral Nutrition in Adults

Arvid E Underman, MD, FACP, DTMH

Clinical Professor of Medicine and Microbiology, Keck School ofMedicine of the University of Southern California, Los Angeles,California; Director of Graduate Medical Education,

Huntington Hospital, Pasadena, CaliforniaSalmonellosis

Utku Uysal, MD

Epilepsy and EEG Fellow, University of Virginia, Charlottesville,Virginia

Seizures and Epilepsy in Adolescents and Adults

David van Duin, MD, PhD

Assistant Professor, Medicine, Cleveland Clinic Lerner College ofMedicine; Staff Physician, Infectious Diseases, Cleveland ClinicFoundation, Cleveland, Ohio

Histoplasmosis

Mary Lee Vance, MD

Professor of Internal Medicine and Neurosurgery and AssociateDirector, General Clinical Research Center, Department ofMedicine, Division of Endocrinology and Metabolism,University of Virginia Health System

Department of Urology, University of Chicago Pritzker School

of Medicine, Chicago, IllinoisRenal Calculi

Blastomycosis

xxi

Todd W Vitaz, MD

Assistant Professor, Department of Neurological Surgery,

University of Louisville School of Medicine; Director of

Neurosurgical Oncology and Co-Director, Neurosciences ICU,

Norton Hospital, Louisville, Kentucky

Management of Head Injuries

Thomas W Wakefield, MD

S Martin Lindenauer Professor of Surgery, Section of Vascular

Surgery, Department of Surgery, University of Michigan, Ann

Arbor, Michigan

Venous Thrombosis

Ellen R Wald, MD

Professor and Chair, Department of Pediatrics, University of

Wisconsin School of Medicine and Public Health;

Pediatrician-in-Chief, American Family Children’s Hospital, Madison,

Wisconsin

Urinary Tract Infections in Infants and Children

Anne Walling, MB, ChB, FFPHM

Professor, Department of Family and Community Medicine,

University of Kansas School of Medicine–Wichita, Wichita,

Kansas

Migraine Headache

Andrew Wang, MD

Associate Professor of Medicine/Cardiology, Duke University

Medical Center, Durham, North Carolina

Infective Endocarditis

Bryan K Ward, MD

Resident Physician, The Johns Hopkins University School of

Medicine, Baltimore, Maryland

Acute Peripheral Facial Paralysis (Bell’s Palsy)

Ruth Weber, MD, MSEd

Clinical Assistant Professor, Department of Family and

Community Medicine, University of Kansas School of

Medicine–Wichita; Associate Program Director, Wesley Family

Medicine Residency, Wichita, Kansas

Pharyngitis

Anthony P Weetman, MD, DSc

Professor of Medicine, The Medical School, University of

Sheffield; Honorary Consultant Endocrinologist, Sheffield

Teaching Hospitals, Sheffield, United Kingdom

Thyroiditis

Arthur Weinstein, MD, FACP, FACR

Professor of Medicine, Georgetown University School of

Medicine; Associate Chairman, Department of Medicine, and

Director, Section of Rheumatology, Washington Hospital

Center, Washington, DC

Lyme Disease

David N Weissman, MD

Adjunct Professor of Medicine and Microbiology (Immunology),

West Virginia University School of Medicine; Director, Division

of Respiratory Disease Studies, National Institute for

Occupational Safety and Health, Morgantown, West Virginia

Pneumoconiosis

Robert C Welliver, Sr., MD

Professor, State University of New York at Buffalo School of

Medicine; Co-Director, Division of Infectious Diseases, Women

and Children’s Hospital of Buffalo, Buffalo, New York

Viral Respiratory Infections

Ryan Westergaard, MD

Postdoctoral Fellow, Division of Infectious Diseases, The JohnsHopkins University School of Medicine, Baltimore, MarylandThe Patient with HIV Disease

Meir Wetzler, MD, FACP

Professor of Medicine and Chief, Leukemia Section, Roswell ParkCancer Institute, Buffalo, New York

Acute Leukemia in Adults

Kimberly Williams, MD

Clinical Assistant Professor, Department of Family andCommunity Medicine, University of Kansas School ofMedicine–Wichita, Wichita, Kansas; Smoky Hill FamilyMedicine Residency, Salinas, Kansas

Otitis Externa

Steven R Williams, MD

Clinical Assistant Professor, Department of Obstetrics andGynecology, The Ohio State University College of Medicine andPublic Health, Columbus, Ohio

Infertility

Tracy L Williams, MD

Clinical Assistant Professor, Department of Family andCommunity Medicine, University of Kansas School ofMedicine–Wichita; Associate Program Director, Via ChristiFamily Medicine Residency, Wichita, Kansas

Chlamydia trachomatis

Elaine Winkel, MD

Associate Professor of Medicine, University of Wisconsin School

of Medicine and Public Health; Attending Cardiologist, HeartFailure and Transplant Program, University of WisconsinHospital and Clinics, Madison, Wisconsin

Heart Failure

Jennifer Wipperman, MD

Assistant Professor, Department of Family and CommunityMedicine, University of Kansas School of Medicine–Wichita,Wichita, Kansas

Dizziness and Vertigo

Michael Wolfe, MD

The Charles H Rammelkamp Jr Professor of Medicine, CaseWestern Reserve University; Chair, Department of Medicine,MetroHealth Medical Center, Cleveland, Ohio

Gastritis and Peptic Ulcer Disease

Gary S Wood, MD

Professor and Chair, Department of Dermatology, University ofWisconsin School of Medicine and Public Health; AttendingPhysician, Veterans Affairs Medical Center, Madison,Wisconsin

Cutaneous T-Cell Lymphomas, Including Mycosis Fungoides and Se´zarySyndrome

Jamie R.S Wood, MD

Instructor in Pediatrics, Harvard Medical School; ResearchAssociate, Sections on Genetics and Epidemiology and VascularCell Biology; Staff Physician, Pediatric, Adolescent, and YoungAdult Section, Joslin Diabetes Center, Boston, MassachusettsDiabetes Mellitus in Children and Adolescents

Jon B Woods, MD

Associate Professor of Pediatrics, Uniformed Services University ofthe Health Sciences, F Edward Hebert School of Medicine,Bethesda, Maryland; Pediatric Infectious Diseases, Wilford HallMedical Center, Lackland Air Force Base, San Antonio, TexasAnthrax

xxii

Steve W Wu, MD

Assistant Professor, University of Cincinnati College of Medicine;

Assistant Professor, Cincinnati Children’s Hospital Medical

Center, Cincinnati, Ohio

Gilles de la Tourette Syndrome

Elizabeth Yeu, MD

Assistant Professor of Ophthalmology, Cullen Eye Institute,

Baylor College of Medicine, Houston, Texas

Vision Correction Procedures

James A Yiannias, MD

Associate Professor and Chair, Department of Dermatology, Mayo

Clinic Scottsdale, Scottsdale, Arizona

Contact Dermatitis

Ronald F Young, MD

Medical Director, Swedish Radiosurgical Center, Swedish Medical

Center and Swedish Neuroscience Institute, Seattle, Washington

Trigeminal Neuralgia

Jami Star Zeltzer, MD

Associate Professor, Department of Obstetrics and Gynecology,Division of Maternal-Fetal Medicine, University of

Massachusetts Medical School, Worcester, MassachusettsVaginal Bleeding in Late Pregnancy

Epilepsy in Infants and Children

xxiii

A colleague recently said that when he finished medical school

many years ago, his father, also a physician, gave him two pieces

of advice: “If you remember the art of medicine and use this

text-book, you will stay out of trouble!” The book: Conn’s Current

Therapy

Whether this advice is altogether sage today is doubtful But

Conn’s Current Therapy remains a bestselling source of desktop

and online information for the busy practicing physician Family

physicians and general internists use Conn’s Current Therapy

for easy-to-access practical information about day-to-day

prob-lems in patient care, for a quick review of advances in clinical

med-icine, and to study for their maintenance of certification Surgical

specialists such as general surgeons, orthopedic surgeons, and

oph-thalmologists buy the book as a comprehensive reference for

up-to-date background information on a wide variety of medical

topics

In its 64 years of publication, there have been only four editors

When Dr Thomas Conn died suddenly in 1994, Robert Rakel,

MD, signed on as editor He was joined by co-editors Edward T

Bope, MD, in 2001 and Rick D Kellerman, MD, in 2010 This

64th edition marks the first that has not been co-edited by either

Dr Conn or Dr Rakel We are honored to continue the tradition

established by Dr Conn and Dr Rakel

Recent changes in the book include expanded online options

such as electronic access to previous editions and convenient

key-word searchability, new topics, a revised table of contents,

time-saving tables and graphs, figures that highlight important

in-formation, and quick-reference Current Diagnosis and Current

Therapy boxes

What will not change is the melding of evidence-based medicinewith the best practices of expert clinicians This makes the bookunique Each chapter is updated every year by authors who are rec-ognized for their expertise Each author explains his or her

“method,” bringing a practical tone to each chapter The authorsare committed to providing up-to-date information Each chapter

is, indeed, an “expert consult.”

Miriam Chan, Pharm D, is an invaluable help in reviewing themanuscripts that go into this book Dr Chan checks each drugdosage and formulation The book uses both generic and tradenames so they are familiar to the clinician Footnotes are addedwhen a drug has not been FDA approved for an indication Dosagesoutside the usual FDA-approved range are similarly footnoted.The editorial staff at Elsevier, particularly Kate Dimock, JoanRyan, and the copy editors, are the best in the business We thankthem for their help with this project

We sincerely appreciate the authors who write each chapter.Many have become friends, oftentimes over e-mail, during theediting process We are amazed at how an invitation to write forConn’s Current Therapy is met with a distinct and proud “Ofcourse, I will!” response Authors are chosen based on recommen-dations from other experts for their clinical expertise as well astheir scholarly activity and research

Finally, we want to thank our families for their patience while

we devote time to making Conn’s Current Therapy a clinicallyvaluable “go-to” book

Edward T Bope, MDRick D Kellerman, MD

1 Symptomatic Care Pending

• A thorough history and physical examination are needed to

exclude secondary medical causes of constipation

• Review the patient’s medication lists to evaluate for

medica-tions that can cause constipation

• Patients with alarm symptoms such as weight loss,

gastrointes-tinal bleeding, and anemia and patients 50 years and older need

a thorough evaluation with radiography or endoscopy

• Patients who fail conservative medical management should

be referred to a specialist for further diagnostic evaluation

inclu-ding colonic motility, anorectal manometry, defacography, and

balloon expulsion test to assess colonic transit and anorectal

function

CURRENT THERAPY

• If a secondary cause of constipation is identified, eliminating

the offending medication or treating the underlying medical

condition can relieve the constipation

• Counseling on normal bowel habits and simple lifestyle

changes such as increasing dietary fiber can improve bowel

regularity

• Empiric treatment with fiber and laxatives can increase bowel

movement frequency and improve symptoms of constipation

• Biofeedback therapy is the treatment of choice for pelvic floor

dysfunction

• Surgery is reserved for patients proved to have slow colonic

transit constipation without small bowel motility delay or pelvic

floor dysfunction

Constipation is a common complaint and accounts for about

2.5 million physician visits annually The estimates of the

preva-lence of constipation vary widely from 2% to 28%, with

increas-ing prevalence in older adults, women, and persons from lower

socioeconomic levels

Definition

Physicians generally define constipation as having fewer than three

bowel movements per week; however, patients might also consider

hard stools, excessive straining, or a sense of incomplete

evacua-tion to be constipaevacua-tion An internaevacua-tional working group of experts

has revised a consensus definition of constipation, known as the

Pathophysiology

Constipation can be divided into primary or secondary disorder Athorough medical history and physical examination are needed toexclude constipation secondary to an underlying medical condi-

can be classified into three groups: normal-transit constipation,slow-transit constipation, and pelvic floor dysfunction Normaltransit constipation, also known as functional constipation, occursmost commonly In functional constipation, stool passes throughthe colon at a normal rate Slow-transit constipation, colonic iner-tia, is a colonic motor disorder characterized by prolonged delay inthe passage of stool through the colon Pelvic floor dysfunction isthe inefficient coordination of the pelvic musculature in the emp-tying of stool from the rectum The cause for pelvic floor dysfunc-tion is unclear, but is likely multifactorial

Clinical Features and Diagnosis

Secondary medical conditions may be excluded with a thoroughhistory and physical examination, as well as specific laboratorytests such as metabolic panel and thyroid function test A bariumenema or colonoscopy may be indicated to exclude structuraldiseases such as colon cancer, especially in patients age 50 yearsand older Alarm symptoms such as weight loss, gastrointestinalbleeding, and anemia also necessitate a thorough evaluationwith radiography or endoscopy A comprehensive review of thepatient’s medication lists, including prescription and over-the-counter medications, is important Medications are a commonsecondary cause of constipation, especially those that affect thecentral nervous system, nerve conduction, and smooth musclefunction

Patients with normal or slow-transit constipation might plain of abdominal bloating and infrequent bowel movements

com-A colonic transit marker study is useful once secondary causesare excluded to differentiate normal transit, slow transit, or pelvicfloor dysfunction Slow transit is characterized by markedlydelayed colonic transit time Pelvic floor dysfunction is character-ized by normal transit time but stagnant markers in the rectum

Patients with pelvic floor dysfunction are more likely to complain

of a feeling of incomplete evacuation, a sense of obstruction, and aneed for digital manipulation Additional studies to diagnosepelvic floor dysfunction are anal manometry demonstratinginappropriate contraction of the anal sphincter during straining,impaired expulsion of barium in defecography, and impairedballoon expulsion from the rectum

TreatmentGeneral Measures for Treating Constipation

If a secondary cause of constipation is identified, treating theunderlying medical condition or eliminating certain medicationsmight relieve the constipation Otherwise, initial managementshould begin with nonpharmacologic methods to improvebowel regularity but may proceed to the use of laxatives torelieve constipation Patients who fail conservative medical man-agement should be referred to a specialist for further diagnosticevaluation

1

Nonpharmacologic Treatments

Counseling on normal bowel habits and simple lifestyle changes

might improve bowel regularity Having a bowel movement may

be partly a conditioned reflex, and patients should be educated

on recognizing and responding to the urge to defecate Patients

should be encouraged to attempt to stimulate defecation first thing

in the morning when the bowel is 2 to 3 times more active and 30minutes after meals to take advantage of the gastrocolic reflex

In Western society, inadequate fiber intake is a common reason forconstipation The daily recommended fiber intake is 20-35 g perday If fiber intake is substantially less, patients should be encour-aged to increase their intake of fiber-rich foods such as bran, fruits,vegetables, and nuts The recommendation is to increase fiber by 5 gper day until reaching the daily recommended intake Adding fiber

to the diet too quickly can cause excessive gas and bloating.Adequate hydration and physical activity is considered impor-tant in maintaining bowel motility, but there has been inconsistentevidence that hydration and regular exercise relieves constipation

Pharmacologic Treatment

There are few studies comparing specific treatment approaches forconstipation There are limited data about the superiority amongthe various treatments and the long-term benefits and harms of lax-atives and fiber preparations There are no evidence-based guide-

Bulk laxatives can contain soluble (psyllium [Metamucil],

[Citrucel]) products Both types absorb water from the intestinallumen and increase stool mass and soften the stool consistency.Patients with normal-transit constipation have the most benefit,but slow-transit constipation or functional outlet problems mightnot be relieved with bulking agents Similar to increasing fiber-richfoods, bloating and excessive gas production may be a complica-tion of bulk laxatives

Emollient laxatives or stool softeners such as docusates (Colace,Surfak) act by lowering surface tension, allowing water to pene-trate and soften the stool They are generally well tolerated butare not as effective in the treatment of constipation Stool softenersmay be more useful for patients with anal fissures or hemorrhoids

Box 2 Medical Causes of Secondary Constipation

Endocrine and Metabolic Diseases

Colonic mass lesions, strictures

Anal fissures, strictures, hemorrhoids

Inflammatory bowel disease

Rectal prolapsed or rectocele

Box 3 Medications Commonly Associated

with Secondary Constipation

Antacids: aluminum, calcium, bismuth

Methylcellulose (Citrucel) 1 tbsp, qd-tid Polycarbophil (Fibercon, Konsyl) 2–4 tabs/day Wheat dextrin (Benefiber) 1–2 tsp, qd-tid Guar gum7

Stool Softner Docusate sodium (Colace) 100 mg bid Docusate calcium (Surfak) 240 mg daily Osmotic Laxatives

Magnesium hydroxide (Milk of Magnesia)

30–60 mL daily Magnesium citrate 296 mL (0.5–1 bottle) daily

Polyethylene glycol 3350 (MiraLax) 3 17 g qd-bid Stimulant Laxatives

Bisacodyl (Ducolax, Correctol) 5–15 mg qd

Prokinetic Agents Tegaserod (Zelnorm) *

New Agent

3 Exceeds dosage recommended by the manufacturer.

7 Available as a dietary supplement.

*Suspended from marketing in March 2007.

tab, tablet.

7 Available as dietary supplement.

Box 1 ROME III Criteria for Functional Constipation

Must include 2 or more of the following:

• Straining during at least 25% of defecations

• Lumpy or hard stools in at least 25% of defecations

• Sensation of incomplete evacuation for at least 25% of

defecations

• Sensation of anorectal obstruction or blockage for at least

25% of defecations

• Manual maneuvers to facilitate at least 25% of defecations

• Fewer than three defecations per week

• Loose stools are rarely present without the use of laxatives

There are insufficient criteria for irritable bowel syndrome

Note: Criteria must be fulfilled for the last 3 months, with

symptom onset at least 6 months before diagnosis

that cause painful defecation Mineral oil is not recommended due

to the potential risk of aspiration

Saline or osmotic laxatives, such as magnesium salts, cause

se-cretion of water into the intestinal lumen by osmotic activity In

general, these agents are thought to be relatively safe because they

work within the colonic lumen and do not have a systemic effect

However, they should be used cautiously in patients with

conges-tive heart failure and chronic renal insufficiency because they can

precipitate electrolyte imbalance and volume overload

Alternative hyperosmotic laxatives are sorbitol, lactulose

(Cephulac), and polyethylene glycol (PEG) 3350 (MiraLax)

Sor-bitol and lactulose are indigestible agents that are metabolized by

bacteria to hydrogen and organic acids Poor bacterial absorption

of these agents can lead to flatulence and abdominal distention

PEG is not degraded by bacteria and is associated with less

abdom-inal discomfort

The stimulant laxatives include products containing senna

(Seno-kot) and bisacodyl (Dulcolax) These laxatives increase intestinal

motility and stimulate fluid secretion into the bowel They generally

produce bowel movements within hours, but they can cause

abdom-inal cramping due to the increased peristalsis Chronic use of

stimulant laxatives containing anthraquinones (cascara [Black

Draught], senna) can cause a brown-black pigmentation of the

co-lonic mucosa, known as melanosis coli This condition is benign and

might resolve as the stimulant laxative is discontinued

A number of prokinetic agents have been studied for the

and increase stool frequency in constipated patients, but neither

has received FDA approval for this indication

In women with irritable bowel syndrome characterized by

improves stool consistency and frequency However, Tegaserod

was removed from the market in March 2007 due to increased

car-diovascular events

Lubiprostone (Amitiza) is an intestinal chloride channel

activa-tor that promotes intestinal fluid secretion of chloride, enhancing

intestinal motility A common side effect is nausea, which is dose

dependent, occurring in about 30% of patients The long-term

safety of this medication has not been established

Prucalopride is a prokinetic, selective serotonin (5-HT4)

recep-tor agonist, that stimulates colonic motility and transit The most

common side effects are headache, nausea, and abdominial pain

Prucalopride (Resolor) is available in Europe for the treatment of

chronic constipation in women who fail standard laxative therapy

Biofeedback

Biofeedback or pelvic floor retraining is beneficial for patients

with pelvic floor dysfunction Biofeedback is used to emphasize

normal coordination and function of the anal-sphincter and

pel-vic-floor muscles A systematic review of biofeedback studies

revealed an overall success rate of 67%

Surgery

Surgery is considered only in patients proved to have slow colonic

transit constipation without small bowel motility delay or pelvic

floor dysfunction A subtotal colectomy with ileorectostomy is

the procedure of choice for patients with slow-transit constipation

that is persistent and intractable

References

Camilleri M, Kerstens R, Rykx A, et al A placebo-controlled trial of Prucalopride for

severe chronic constipation N Engl J Med 2008;358:2344–54.

Diamant NE, Kamm MA, Wald A, Whitehead WE AGA technical review on

constipa-tion American Gastroenterological Associaconstipa-tion Gastroenterology 1999;116:735–60.

Enck P Biofeedback training in disordered defecation: A critical review Dig Dis Sci

adult patients with chronic constipation: A double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety Aliment Pharm Ther 2007;

25:1351–61.

Koch A, Voderholzer WA, Klauser AG, Muller-Lissner SA Symptoms in chronic stipation Dis Colon Rectum 1997;40:902–6.

con-Lembo A, Camilleri M Chronic constipation NEJM 2003;349:1360–8.

Longstreth GF, Thompson WG, Chey WD, et al Functional bowel disorders enterology 2006;130:1480–91.

Gastro-Muller-Lissner SA, Fumagalli I, Bardhan KD, et al Tegaserod, a 5-HT 4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation Aliment Pharmacol Ther 2001;15:1655–66.

Prather CM, Ortiz-Camacho CP Evaluation and treatment of constipation and fecal impaction in adults Mayo Clin Proc 1998;73:881–996.

Rao SSC Constipation: Evaluation and treatment Gastroenterol Clin North Am 2003;32:659–83.

Schiller LR Constipation and fecal incontinence in the elderly Gastroenterol Clin North Am 2001;30:497–515.

Stocchi L, Pemberton JH Surgical management of constipation In: Cameron JL, editor Current Surgical Therapy St Louis: Mosby; 2001 p 260–4.

Tramonte SM, Brand MB, Mulrow CD, et al The treatment of chronic constipation

in adults: A systematic review J Gen Intern Med 1997;12:15–24.

Voderholzer WA, Schtke W, Mihldorfer BE, et al Clinical response to dietary fiber treatment of chronic constipation Am J Gastroenterol 1997;92:95–8.

COUGH

Method ofDavid G Hill, MD

CURRENT DIAGNOSIS

All Patients Presenting With Cough

• Perform thorough history and physical examination

• Review timing and nature of cough along with exacerbating

or mitigating factors

• Review prior history of cough, allergies, asthma, or esophageal reflux

gastro-• Take medication history, particularly use of ACE inhibitors

• Focus physical examination on head, neck, and thorax

Patients With Postinfectious or Chronic Cough

• Obtain chest radiograph, particularly in patients with an mal respiratory examination

abnor-• Evaluate airflow obstruction with spirometry

• Stop ACE inhibitors and assess for improvement

• Administer empiric therapy for postnasal drip, asthma, orgastroesophageal reflux

• Consider methacholine challenge testing to evaluate for airwayhyperreactivity

• Induce sputum for eosinophils or empiric trial of steroids for eosinophilic bronchitis

cortico-• If cough persists, consider esophagoscopy, 24-hour pH probemonitoring, high-resolution chest CT, or bronchoscopy

Abbreviations: ACE ¼ angiotensin-converting enzyme; CT ¼computed tomography.

CURRENT THERAPY

Treatment of Acute Cough

• Common cold: Supportive care with over-the-counter gestant and cough suppressant or ipratropium nasal spray(Atrovent, 0.06%), two 42-mcg sprays in each nostril 3 timesdaily for 4 to 7 d depending on duration of symptoms

decon-• Acute sinusitis: Treat as a common cold Add oxymetazoline(Afrin), two sprays twice daily for three days If symptoms

1 Not FDA approved for this indication.

2

Not available in the United States.

3

persist, consider antibiotic therapy directed against

Haemophi-lus influenzae and Streptococcus pneumoniae such as

azithromy-cin (Zithromax), 500 mg daily for 3 d

• Exacerbation of chronic obstructive pulmonary disease:

7 d such as clarithromycin (Biaxin), 500 mg twice daily for 7 d;

systemic corticosteroids such as prednisone (Deltasone),

40 mg tapered over 10 d; inhaled anticholinergics such as

tiotropium (Spiriva), one inhalation daily; and short-acting

b-agonists such as albuterol (Proventil), two inhalations every

4 h as needed; smoking cessation

• Allergic rhinitis: Nasal corticosteroids such as mometasone

(Nasonex), two sprays in each nostril daily; nonsedating

anti-histamines such as fexofenadine (Allegra), 180 mg daily;

aller-gen avoidance if possible

• Bordetella pertussis: Erythromycin 500 mg four times daily for

14 d or trimethoprim 160 mg/sulfamethoxazole (Bactrim

are likely effective and may be better tolerated

Treatment of Postinfectious Cough

and pseudoephedrine, 120 mg for up to 3 wk; ipratropium

(Atrovent), 0.06% nasal spray for up to 3 wk; azelastine (Astelin)

nasal spray (137 mcg), two sprays each nostril twice daily for

up to 3 wk

• Bronchospasm: Inhaled corticosteroid such as budesonide

long-acting b-agonist such as formoterol (Foradil), two

inhala-tions twice daily; short-acting b-agonist such as albuterol

(Ven-tolin), two puffs every 4 h as needed Oral steroids such as

prednisone (Deltasone), 40 mg tapered over 10 d

• Bordetella pertussis: Erythromycin, 500 mg four times daily for

14 d, or trimethoprim 160 mg/sulfamethoxazole, 800 mg

likely effective and may be better tolerated

• Bacterial sinusitis: Dexbrompheniramine, 6 mg, and

pseudo-ephedrine (Drixoral Cold and Allergy Tablets), 120 mg for up

to 3 wk; oxymetazoline (Afrin), two sprays twice daily for 3 d;

azithromycin (Zithromax), 500 mg daily for 3 d

• Chlamydia/mycoplasma: Clarithromycin (Biaxin), 500 mg twice

daily for 14 d

Treatment of Chronic Cough

• Postnasal drip syndrome

Nonallergic: Dexbrompheniramine, 6 mg, and

pseudoephed-rine, 120 mg for up to 3 wk; ipratropium (Atrovent),

0.06% nasal spray for up to 3 wk; azelastine (Astelin) nasal

spray (137 mcg), two sprays each nostril twice daily for up

to 3 wk

Allergic: Fluticasone (Flonase) (50 mcg), two sprays each nostril

daily; fexofenadine (Allegra), 180 mg daily; allergen avoidance

• Asthma: Albuterol (Proventil), two puffs every 4 hours as

needed; inhaled corticosteroid such as budesonide

(Pulmi-cort), two inhalations daily with or without inhaled long-acting

b-agonist such as formoterol (Foradil), two inhalations twice

daily; combination of long-acting b-agonist and inhaled steroid

such as fluticasone/salmeterol (Advair) (100/50 mcg), inhaled

twice daily; montelukast (Singulair), 10 mg daily; prednisone

(Deltasone), 40 mg daily with tapering dose over 10 d

• Gastroesophageal reflux: Dietary and lifestyle modifications,

lansoprazole (Prevacid), 30 mg daily for up to 3 mo;

metoclo-pramide (Reglan), 10 mg before meals and sleep

inhalations twice daily; prednisone (Deltasone), 30 mg daily

for 3 wk

• ACE inhibitor: Discontinue medication

1 Not FDA approved for this indication.

Cough is among the most common presenting complaints of tients in the United States It serves as a protective reflex against for-eign material and as a method to clear secretions from the airway.The cough center is located in the medulla, and the cough reflex ismediated by way of multiple nervous system pathways including thetrigeminal, glossopharyngeal, vagus, and phrenic nerves Cough ismediated by separate neural pathways from bronchoconstriction.When cough occurs there is a synchronized activation of muscles,the glottis opens, and the lungs expand At the peak of inspirationthe glottis closes and expiratory muscles contract This results in in-creased intrathoracic pressure; when the glottis opens airflow canreach 500 miles per hour The cough reflex varies in different patientpopulations Women have a more sensitive cough reflex than men.Smokers’ cough reflexes are depressed despite the increased fre-quency of cough in this population Patients who have a decreasedcough sensitivity following cerebral vascular accidents have an in-creased incidence of pneumonia Angiotensin-converting enzyme(ACE) inhibitors increase cough reflex sensitivity and have beenshown to decrease the risk of pneumonia in patients with cerebro-vascular accidents The evaluation of cough as a patient complaintmay best be pursued by examining the duration of the symptoms.Cough can be subcategorized into acute and chronic cough Coughthat occurs following an acute respiratory infection may narrow thedifferential diagnosis and is addressed separately

outpa-Acute Cough

Acute cough may be defined as cough that has been present for lessthan 8 weeks Because all causes of chronic coughs initially causeacute symptoms, patients with acute cough may actually havecough caused by one of the etiologies discussed later in this section;however, acute cough more commonly is the result of a less indo-

acute cough Most acute cough is the result of viral infections, cifically the common cold Most cough resulting from the commoncold is self-limited and lasts less than 3 weeks Most episodes ofsinusitis are of viral etiology; however, bacterial sinusitis canalso result in acute cough The presence of a significant smokinghistory raises the possibility of an acute exacerbation of chronicobstructive pulmonary disease (COPD) as the cause of acutecough, especially in patients with previously documented COPD.Bordetella pertussis infection may also be the etiology of an acuteepisode of cough Noninfectious processes that lead to acute coughinclude allergic rhinitis, congestive heart failure, asthma, and aspi-ration The clinical history, physical examination, and diagnostictesting are of particular importance in differentiating these diseasestates and often point to the diagnosis

spe-Postinfectious Cough

Postinfectious cough begins with an acute upper respiratory tractinfection but persists following the resolution of the other acute

Box 1 Causes of Acute Cough

• Viral upper respiratory infections (the common cold)

• Acute sinusitis (usually viral, occasionally bacterial)

• Exacerbation of chronic obstructive pulmonary disease

• Allergic rhinitis

• Bordetella pertussis infection

Box 2 Causes of Postinfectious Cough

• Postnasal drip syndrome

the common cold or sinusitis Bronchospasm may lead to

postin-fectious cough either as a result of a single episode of

postinfec-tious wheezing or an exacerbation of underlying asthma

Postinfectious cough may be the initial presentation of asthma

Re-current episodes of airflow obstruction are required to confirm the

diagnosis of this chronic illness Because B pertussis can present

with an indolent course, this infection can be confused with a

post-infectious cough Similarly, bacterial sinusitis can be confused with

postinfectious cough Both of these etiologies of cough are the

re-sult of ongoing infection rather than true postinfectious cough

Mycoplasma pneumoniae and Chlamydia pneumoniae infections

may also result in postinfectious cough likely because of persistent

airway inflammation and increases in cough reflex sensitivity

Chronic Cough

Chronic cough presents the most difficult diagnostic dilemma for

the health care practitioner Cough of greater than 8 weeks’

dura-tion can be considered chronic Lesser duradura-tion of symptoms may

still be indicative of one of the etiologies discussed in this section,

but such cough is more likely the result of one of the infectious or

postinfectious etiologies described previously In patients who

have never smoked, chronic cough is most likely the result of

asthma, postnasal drip syndrome, or gastroesophageal reflux

These three etiologies are the most common cause of chronic

cough regardless of patient age In nonsmokers with a normal

chest radiograph who are not taking an ACE inhibitor, these three

etiologies alone or in combination are the cause of more than 85%

common of these etiologies Cough may be the sole presenting

symptom of any of these conditions; they are not mutually

exclu-sive and may coexist, particularly in the patient with troublesome,

persistent symptoms Most patients with problematic, persistent

cough have multiple etiologies contributing to their symptoms

COPD must be considered in current smokers and in those patients

with a significant smoking history Smokers can have a cough of

any etiology, however, and it should not be assumed that their

cough is the result of smoking or COPD Although smokers

fre-quently admit to cough when a history is taken, they infrefre-quently

seek medical attention for this symptom Cough resulting from the

use of ACE inhibitors must be considered in all patients being

trea-ted with these medications Less common, yet frequent causes of

cough include chronic bronchitis from irritants other than tobacco

smoke and eosinophilic bronchitis Occasionally, chronic cough

may be the result of:

• Congestive heart failure

• Chronic infection, such as tuberculosis or Mycobacterium

avium complex

• Recurrent aspiration because of pharyngeal or esophageal

abnormalities

Key Diagnostic Points

The evaluation of acute cough should focus on the history and

physical examination Most acute cough will be the result of

self-limited viral upper respiratory infections More thorough

evaluation is necessary in the workup of cough of longer durationparticularly if the cough has been present for more than 2 months

The history of onset of the cough and whether it was associatedwith an acute infectious episode should be elicited Exposure tosick contacts particularly to a known case of B pertussis are impor-tant historic considerations The timing and nature of the coughand any associated sputum must be described Factors that miti-gate or worsen the cough should be examined, and prior history

of episodic cough, allergies, wheezing, asthma, and geal reflux should be questioned A thorough medication historyparticularly regarding use of ACE inhibitors must be obtained En-vironmental factors both at home and in the work place should bereviewed Although smoking history is important, it is again notedthat smoking-related cough is an infrequent reason for a patient toseek medical attention The physical examination should focusmost on the head, neck, and thorax with a thorough examination

gastroesopha-of the upper respiratory tract including the auditory canal, nose,and oropharynx The cardiopulmonary examination should also

be thorough to elicit signs of less common illnesses

Acute cough associated with an acute respiratory illness andprominent upper airway symptoms can be assumed to be second-ary to the common cold Diagnostic testing is not indicated in suchpatients; a chest radiograph would be normal and is thus notrecommended Patients who have abnormal sinus transillumina-tion, purulent nasal secretions, sinus pain or tenderness, or maxil-lary toothache could possibly have bacterial sinusitis Again, a viraletiology of sinusitis is more likely than bacterial sinusitis, and an-tibiotic therapy should be initiated only in patients with persistentsymptoms despite symptomatic therapy Patients with documentedCOPD who present with acute cough, purulent sputum, dyspnea,and wheezing have an exacerbation of their underlying COPD andshould be treated appropriately Allergic rhinitis usually presentswith a clear clinical history of episodic nasal and other allergysymptoms, and allergen avoidance can be initiated It is important

to note that allergic rhinitis can present with perennial symptoms

Postinfectious cough should be evaluated with thorough tory and physical examinations followed by limited diagnosticevaluation and empiric therapies Patients should be treated forpostnasal drip syndrome, particularly in the setting of describedrhinitis, postnasal drip, or frequent throat clearing The presence

his-of nasal inflammation and congestion, cobblestoning his-of the ryngeal mucosa, or mucus in the oropharynx should also lead toempiric therapy for postnasal drip syndrome If cough persists

pha-in the patients with suspected postnasal drip syndrome, evaluation

of the sinuses with imaging and treatment of those patients withevidence of bacterial sinusitis should be pursued Computed to-mography (CT) imaging of the sinuses is the gold standard fordiagnosing bacterial sinusitis Patients with postinfectious coughand an abnormal respiratory examination should have a chest ra-diograph Patients with a normal radiograph and evidence ofbronchospasm can be empirically treated for airway hyperreactiv-ity Again, the diagnosis of asthma requires recurrent airflow ob-struction and cannot be made on the basis of a single episode ofpostinfectious wheezing or airway hyperreactivity In subjectswith cough and vomiting, known exposure to a case of B pertus-sis, or in the presence of a B pertussis epidemic in the community,empiric therapy for this illness should be pursued

Before the vaccine era, B pertussis was an endemic disease,which occurred in cyclic epidemics It has been documented that

B pertussis continues to circulate in the adult population despitecontrol of the disease in the pediatric population by vaccination

Immunity to B pertussis, whether as a result of primary infection

or immunization, is shortlived The longer the elapsed intervalsince prior infection or immunization and repeat infection, themore likely repeat infection will be symptomatic Perhaps repeatadolescent and adult booster immunization programs should beimplemented to effectively control or eliminate this infection

History and physical examinations remain paramount in the tient presenting with chronic cough The majority of patientsshould have a chest radiograph obtained as part of their evalua-tion If the history and physical examination suggest that postnasal

pa-Box 3 Causes of Chronic Cough

• Postnasal drip syndrome

drip, asthma, or gastroesophageal reflux is the etiology of a

pa-tient’s symptoms, empiric therapy for these conditions should be

initiated Cough triggered by environmental factors or changes

may be secondary to rhinitis and postnasal drip or airway

hyper-reactivity and asthma Substernal burning or a sour taste in the

mouth, particularly when triggered by supine positioning or

bend-ing, should increase the suspicion of gastroesophageal reflux

If asthma is suspected, spirometry should be performed to

docu-ment whether airflow obstruction is present Response to inhaled

bronchodilator with normal spirometry is indicative of airway

hyperreactivity Improvement in symptoms and spirometry with

em-piric asthma therapy even in the setting of normal baseline flow rates

also confirms an asthmatic etiology A methacholine challenge can

be performed to confirm airway hyperreactivity If cough in the

set-ting of a positive methacholine challenge shows absolutely no

re-sponse to empiric asthma therapy with inhaled corticosteroids

and bronchodilators, consider a trial of systemic steroids If the

cough does not respond to aggressive asthma therapy, the

methacho-line challenge test results were probably false positive; asthma

ther-apy can be discontinued and diagnostic efforts focused elsewhere

Cough patients being treated with ACE inhibitors should cease

these medications Up to 30% of patients treated with ACE

inhibi-tors will develop a persistent cough, more commonly in women,

nonsmokers, and patients of Chinese ancestry It may take 4 weeks

or more for cough caused by ACE inhibitors to resolve following

ces-sation of these medications In the presence of ACE inhibitor use,

further evaluation of dry cough should not be pursued until the

patient has been withdrawn from these medications for 1 month

An abnormal chest radiograph can direct further diagnostic

studies and therapies, whereas a normal chest radiograph makes

less common etiologies of chronic cough such as carcinoma,

con-gestive heart failure, sarcoidosis, or interstitial lung disease

un-likely Evidence of basilar infiltrates or fibrosis may suggest

interstitial lung disease or chronic aspiration Severe

gastroesoph-ageal reflux must be considered in those patients with

radio-graphic evidence of chronic aspiration

Chronic cough without a definitive etiology can be troubling to

both patient and health care provider A systematic approach can

stressed that such a cough may be the result of multiple etiologic

factors In the absence of specific factors that help to point to an

etiology of chronic cough, empiric treatment for postnasal drip

syndrome should be pursued Methacholine challenge testing will

rule out asthma if it is negative and should also be performed early

in the evaluation of chronic cough Cough may be the sole

mani-festation of asthma in nearly 60% of patients presenting with

chronic cough A positive methacholine challenge does not have

100% predictive value but should lead to empiric asthma therapy

Empiric therapy for silent gastroesophageal reflux should be

ini-tiated in those who do not respond to treatment for postnasal drip

syndrome and do not have evidence of or respond to treatment for

asthma Cough may be the only manifestation of gastroesophageal

reflux up to 30% of the time Definitive diagnosis of

gastroesoph-ageal reflux requires invasive testing and may require more than

one testing modality Therefore it is recommended that empiric

therapy for reflux be pursued before diagnostic testing Reflux

therapy should include conservative approaches such as dietary

and lifestyle changes, bed positioning, and pharmacologic

treat-ment Gastroesophageal reflux–related cough can be particularly

troublesome and persistent and may take weeks or months to

re-spond to appropriate and intensive antireflux therapy This may

include higher-than-normal doses of proton pump inhibitors and

promotility agents Surgical treatment of reflux may be necessary

to effectively treat reflux related cough in some patients In

pa-tients with persistent cough, the common etiologies of cough often

coexist and exacerbate one another Therapy should often be

ad-ditive, for instance treating both asthma and reflux, rather than

mutually exclusive Persistent cough should result in further

diag-nostic evaluation including sputum studies, esophagoscopy,

24-hour pH probe esophageal monitoring, high-resolution chest

CT, and possibly bronchoscopy In the presence of normal chest

imaging, bronchoscopy is unlikely to yield beneficial diagnostic formation in the patient with chronic cough

in-Eosinophilic bronchitis in the absence of asthma is also a quent cause (up to 13% of cases) of chronic cough Patients witheosinophilic bronchitis will have normal spirometry and a negativemethacholine challenge The disease may be diagnosed by appro-priate induced sputum analysis showing at least 3% eosinophils.Alternatively it can be empirically treated with a course of inhaledcorticosteroids Most patients appear to respond to inhaled corti-costeroids within 3 weeks Systemic corticosteroids may be re-quired to improve the symptoms in some cases There may be

fre-an association of gastroesophageal reflux with eosinophilic chitis Patients with gastroesophageal reflux have been found tohave increased sputum eosinophilia

bron-Bronchiectasis may infrequently result in chronic cough chiectasis is characterized by the abnormal dilatation of one ormore branches of the bronchial tree It can effectively be diagnosed

Bron-by high resolution CT scan of the thorax Bronchiectasis may cur following a severe infection, distal to an area of airway ob-struction, congenitally, from chronic inflammatory processes,and as a result of chronic parenchymal scarring and traction Pa-tients with bronchiectasis may present with productive or nonpro-ductive coughs They may have recurrent episodes of infectionresulting from persistent colonization of the abnormal bronchialsegment Infectious agents may include routine bacterial organ-isms and typical or atypical mycobacterium Bronchiectasis may

oc-be seen in a variety of chronic illnesses The presence of ectasis in a patient without a known predisposing cause shouldprompt the clinician to look for appropriate clinical states such as:

bronchi-• Primary or acquired immunodeficiencies

• Abnormalities of ciliary function, such as ciliary dyskinesia orcystic fibrosis

• Postinfectious inflammatory processes, such as allergic pulmonary aspergillosis

broncho-Is patient on ACEinhibitor?

Stop medicine andobserve for up to 4weeks If coughpersists

Treat empirically forpostnasal drip syndrome

If cough persists after

3 weeks

Pursue methacholinechallenge testing

Is test positive?

Treat for asthma

If no response

to aggressivetherapy

Treat forgastroesophageal reflux

If no responseafter 3 weeks

Pursue further diagnosticevaluation includingesophagoscopy, 24-hour

pH probe esophagealmonitoring, high-resolutionchest CT, and possiblybronchoscopy

Abbreviations: ACE ¼ angiotensin-converting enzyme; CT ¼ computed tomography.

• Collagen vascular diseases

• Inflammatory bowel disease

• Sarcoidosis

• Yellow nail syndrome

The presence of localized bronchiectasis may be an indication to

pursue flexible fiberoptic bronchoscopy to rule out an obstructing

lesion and to obtain appropriate culture specimens Treatment of

bronchiectasis is aimed at the underlying disease state if one can be

identified Infections should be treated with appropriate

antibi-otics Clearance of bronchial secretions can be aided with

muco-lytics and chest physiotherapy including use of percussive

devices In some cases surgical therapy to remove the

bronchiecta-tic segment can be considered

Treatment

The key treatments for cough are best described based on the

sus-pected etiology Acute cough therapy should focus on supportive

treatment of the underlying suspected etiology, which will likely

be a viral upper respiratory infection Therapy for exacerbation

of chronic obstructive pulmonary disease, allergic rhinitis, bacterial

sinusitis, or B pertussis infection is more specific Postinfectious

cough should focus on therapy for postnasal drip syndrome or

air-ways reactivity if suspected In chronic cough of uncertain etiology

(seeFigure 1), cough therapy should begin with empiric treatment

of postnasal drip syndrome, evaluation and treatment of asthma,

empiric treatment of gastroesophageal reflux syndrome, and finally

evaluation or empiric therapy for eosinophilic bronchitis

Cough is a frequent and troublesome symptom for both patient

and health care provider Acute cough although at times troubling

is usually self-limiting Postinfectious cough and chronic cough are

more problematic, but can effectively be evaluated and treated by

performing a thorough history and physical examination and

pur-suing a systematic approach to diagnostic evaluation and both

em-piric and guided therapies The resolution of chronic troubling

cough is a therapeutic relief for the patient and a gratifying

expe-rience for the caregiver

References

Barnes TW, Afessa B, Swanson KL, Lim KG The clinical utility of flexible

bronchos-copy in the evaluation of chronic cough Chest 2004;126:268–72.

Breitling CE, Ward R, Goh KL Eosinophilic bronchitis is an important cause of

chronic cough Am J Respir Crit Care Med 1999;160:406–10.

Cherry JD Epidemiological, clinical, and laboratory aspects of pertussis in adults.

Clin Infect Dis 1999;28(Suppl2):S112–7.

Cohen M, Sahn SA Bronchiectasis in systemic diseases Chest 1999;116:1063–74.

Irwin RS, Madison JM Symptom research on chronic cough: A historical

perspec-tive Ann Intern Med 2001;134:809–14.

Irwin RS, Madison JM The diagnosis and treatment of cough N Engl J Med

2000;343:1715–21.

Irwin RS, Madison JM The persistently troublesome cough Am J Respir Crit Care

Med 2002;165:1469–74.

Kiljander TO The role of proton pump inhibitors in the management of

gastroesoph-ageal reflux disease-related asthma and chronic cough Am J Med 2003;115(3A):

• Benign paroxysmal positional vertigo

• Repeated, brief episodes lasting less than 1 minute

• Triggered by changes in head position

• Positive Dix-Hallpike maneuver

• Up-beating torsional nystagmus is seen after positional

changes or the Dix-Hallpike maneuver

• Vestibular neuritis

• Single, severe, constant episode lasting days

• Subacute onset

• Positive head thrust test

• Nystagmus is unilateral, horizontal, and spontaneous

• Me´nie`re’s disease

• Recurrent episodes of vertigo lasting hours

• May have unilateral hearing loss, tinnitus, or ear fullness

• Red flags for stroke include:

• Sudden onset

• Risk factors for stroke

• Nystagmus with a central pattern

• Negative head-thrust test

• Additional neurologic signs

• Inability to walk

CURRENT THERAPY

• Benign paroxysmal positional vertigo

• The canalith repositioning procedure (Epley maneuver) is themost effective treatment

• Vestibular rehabilitation is effective

• Consider observation with close follow-up if a patient will nottolerate the canalith repositioning procedure or if symptomsare mild

• Avoid symptomatic medications

• 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 clinicalmedicine 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 ular neuritis and benign paroxysmal positional vertigo (BPPV)

vestib-Life-threatening central causes include stroke, vertebrobasilar sufficiency, demyelinating disease, and an intracranial mass Thefirst step in evaluating vertigo is differentiating among the fourtypes of dizziness: near syncope or light-headedness, disequilib-rium, psychogenic dizziness, and true vertigo True vertigo is afalse sense of motion, and patients typically report that “the room

in-is spinning.” Thin-is chapter will focus on the two most commoncauses of episodic vertigo: BPPV and vestibular neuritis

Epidemiology

Vertigo is a common office complaint In fact, 7.5 million cans are evaluated for dizziness in ambulatory care settings eachyear, and approximately 50% of these cases are vertigo In primarycare office settings, BPPV accounts for 42% of vertigo diagnoses,followed by vestibular neuritis (41%), Me´nie`re’s disease (10%),and vascular causes (3%) BPPV is the most common vestibulardisorder across the lifespan

Ameri-Risk Factors

BPPV is seven times more likely in individuals over age 60, and it isalso more common in women A history of prior head trauma andother vestibular disorders place patients at risk for BPPV There are

no identified risk factors for vestibular neuritis

Pathophysiology

BPPV is thought to occur when calcium carbonate debris nia) are dislodged and float freely in the semicircular canals of theinner ear The posterior canal is most often involved During headmovement, loose otoconia move in the canal and cause a

7

continued sense of motion for a few seconds until they settle The

pathophysiology of vestibular neuritis is uncertain Evidence

sup-ports a viral infection, most likely HSV-1, which causes

inflamma-tion 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 posidura-tional 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

mi-graines can have a familial preponderance, and a family history

of these disorders should be elicited Many medications, including

anticonvulsants and antihypertensives, cause dizziness

BPPV causes brief, recurrent episodes that last less than 1 minute

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

vomit-ing can be severe durvomit-ing the first few days Patients with vestibular

neuritis 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 are

normal 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-thrust test, and

Patients with vestibular neuritis may have difficulty walking,

but the inability to walk is a red flag for a central lesion

Nystag-mus is unidirectional (always beats in the same direction) and

hor-izontal in vestibular neuritis, and is suppressed by visual fixation

Having a patient focus on an object in the room will stop the

nys-tagmus, 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 down-beating

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 peripheral

lesion on the side that the head is turned towards Central lesionswill not cause saccades and the head thrust test will be normal.The Dix-Hallpike maneuver is diagnostic of posterior canal

and vomiting may occur After the patient is placed in thehead-hanging position, there is a 5- to 20-second latency periodbefore the nystagmus and symptoms appear Both the nystagmusand vertigo will increase in severity and then resolve within

60 seconds The nystagmus observed is up-beating and torsional.The maneuver should be repeated with the head held to the op-posite side The side which elicits the symptoms and nystagmusdiagnoses BPPV in the ipsilateral ear If both sides elicit symp-toms, the patient may have bilateral BPPV If the test is negativeand BPPV is strongly suspected, the patient should lie supine andthe examiner can turn the head to each side (supine roll test) Thismaneuver will cause symptoms and nystagmus in patients withhorizontal canal BPPV

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-thrust test The patient maintains visual fixation during head movement (Adapted from Pract Neurol 2008; 8:211–221.)

TABLE 1 Differentiating Peripheral and Central Causes of Vertigo

lasting less than 1 minute Triggered by positional changes

No vertigo between attacks

Subacute onset Constant and severe vertigo lasting days

Nausea and vomiting may be severe

Sudden onset Risk factors for stroke May have severe headache

Down-beating Pure torsional

Specialized physical examination

aphasia, incoordination, weakness, or numbness)

BPPV and vestibular neuritis are diagnosed clinically Further

diag-nostic testing is indicated if the diagnosis is uncertain or a central

cause is suspected Audiometry may be abnormal in Me´nie`re’s

dis-ease MRI is the best imaging test for central lesions because it

in-cludes the posterior fossa and is most sensitive for stroke

Vestibular function testing is useful if the diagnosis is unclear or

in cases of refractory vertigo Vestibular function testing includes

several different specialized tests that evaluate the ocular and

ves-tibular 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

pa-tients with BPPV may have additional vestibular disorders causing

vertigo that vestibular function testing can elucidate

Differential Diagnosis

Me´nie`re’s disease is the third most common cause of vertigo, and is

suspected in patients with the triad of tinnitus, fluctuating hearing

loss, and vertigo Episodes usually last hours, are disabling, and

are recurrent over years Migrainous vertigo features episodes lasting

hours in patients with other migraine symptoms such as headache,

photophobia, phonophobia or aura Central lesions such as stroke,

vertebrobasilar insufficiency, or intracranial mass are most

concern-ing Red flags for stroke include sudden onset, risk factors for stroke,

associated neurologic signs, inability to walk, negative head-thrust

test, severe associated headache and characteristic nystagmus

Post-traumatic vertigo may occur in patients after head trauma who

pre-sent with vertigo, tinnitus, 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 withsneezing or coughing trigger vertigo attacks Postural hypotensionshould be ruled out in all patients An acoustic neuroma presentswith slowly progressive, unilateral sensorineural hearing loss andtinnitus Many patients may have an unsteady gait, but true vertigo

is rare

Treatment

BPPV is best treated with the canalith repositioning procedure,

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 warnedthat nausea or vomiting may occur during the procedure, and may

be pre-treated with an antiemetic medication The procedure can

be repeated if unsuccessful Posttreatment activity restrictions areunnecessary Vestibular rehabilitation is another valuable treat-ment for BPPV, but it is less effective than the canalith reposition-ing procedure It enhances central compensation for peripheraldeficits and leads to faster symptom recovery than observationalone, though most patients will improve spontaneously after

4 to 6 weeks Observation is an option if symptoms are mild or

if a patient will not tolerate the canalith repositioning procedure

or vestibular rehabilitation However, observation is associatedwith higher recurrence rates than the canalith repositioning proce-dure Vestibular-suppressant medications such as antihistaminesand benzodiazepines are discouraged because they interfere withcentral compensation and increase the risk for falling Surgery israrely needed for BPPV, but may be helpful in refractory cases

Vestibular neuritis is primarily treated with rest, vestibularsuppressant medications, and vestibular rehabilitation Patientsmay initially be admitted if symptoms, such as nausea and vomit-ing, are severe or if stroke is suspected Treatment with antihista-

may be used to treat severe symptoms However, these shouldnot be continued more than 2 to 3 days because they inhibit centralcompensation The use of corticosteroids is controversial Al-though studies show that vestibular-function testing improvesmore quickly in patients treated with corticosteroids, there is noevidence that corticosteroids hasten the recovery of clinical signsand symptoms of vestibular neuritis Antiviral medications havenot been proven effective for vestibular neuritis

For patients with vestibular neuritis, a referral for vestibular habilitation should be given as soon as symptoms improve and apatient can tolerate the exercises Exercises include balance andgait training as well as coordination of head and eye movements

re-Vestibular rehabilitation hastens recovery and improves balance,gait, and vision by increasing central compensation for vestibulardysfunction

Monitoring

Patients diagnosed with BPPV should be reassessed in 1 month gardless of treatment Failure to improve warrants further evalu-ation 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

re-Complications

Patients with BPPV are at increased risk for falls Thirty percent ofelderly patients with BPPV have multiple falls in a year Thus, pa-tients should be assessed for fall risk, functional mobility and bal-ance Home safety evaluation and home supervision should beconsidered BPPV often recurs, with an estimated rate of 15%

per year Counseling patients about recurrence can lead to earlierrecognition, earlier treatment and avoidance of falls Patients withvestibular neuritis are at increased risk for BPPV and Me´nie`re’s dis-ease Vestibular neuritis rarely recurs

1 Not FDA approved for this indication.

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 facing 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 rapidly 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 repeated 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.)

9

Baloh RW Vestibular neuritis N Engl J Med 2003;348:1027–32.

Bhattacharyya N, Baugh RF, Orvida L, et al Clinical practice guideline: Benign

par-oxysmal positional vertigo Otolaryngol Head Neck Surg 2008;139:S47–S81.

Chan Y Differential diagnosis of dizziness Otolaryngol Head Neck Surg 2009;

17:200–3.

Epley JM The canalith repositioning procedure: For treatment of benign paroxysmal

positional vertigo Otolaryngol Head Neck Surg 1992;107:399–404.

Goudakos JK, Konstantinos DM, Franco-Vidal V, et al Corticosteroids in the

treat-ment of vestibular neuritis: A systematic review and meta-analysis Otol Neurotol

2010;31:183–9.

Hamid M Medical management of common peripheral vestibular diseases Curr

Opin Otolaryngol Head Neck Surg 2010;18:407–12.

Hillier SL, Holohan V Vestibular rehabilitation for unilateral peripheral vestibular

dysfunction Cochrane Database Syst Rev 2007;4:CD005397.

Hilton M, Pinder D The Epley (canalith repositioning) manoeuvere for benign

par-oxysmal positional vertigo Cochrane Database Syst Rev 2004;2: CD003162.

Kerber KA Vertigo and dizziness in the emergency department Emerg Med Clin

North Am 2009;27:39–50.

Leveque M, Labrousse M, Siedermann L, et al Surgical therapy in intractable benign

paroxysmal positional vertigo Otolaryngol Head Neck Surg 2007;136:693–8.

Seemungal BM, Bronstein AM A practical approach to acute vertigo Pract Neurol

• The clinical evaluation of fatigue begins with a thorough

med-ical and psychosocial history

• Consider monitoring for a month before beginning a laboratory

evaluation, because it usually does not yield a diagnosis Initial

evaluation should include a CBC, electrolytes, glucose, liver and

kidney function tests, thyroid function tests, and urinalysis

• Among the many possible causes of fatigue, the most common

include depression, environmental stress, anemia, and

diabe-tes In many cases, a cause is not determined

CURRENT THERAPY

• 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

• Symptom relief includes exercise, regular sleep habits, family

dis-cussion 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 symptom

in 21% of all patient encounters While acute, prolonged, and

chronic fatigue are relatively common, chronic fatigue syndrome

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 related problems Perpetuating factors include physical inactivity,emotional disorders, and disturbances of sleep

discom-as similar symptoms ldiscom-asting 6 months or more

Diagnosis

The clinical evaluation begins with a thorough medical and chosocial history It is important to allow the patient to speakuninterrupted for the first minute or two of the interview, becausethis often provides pertinent clues The history should include ex-ploration of all medically unexplained symptoms, inquiry intowork and life stressor issues, questions regarding alcohol andother substance use, and the current use of prescription, over-the-counter, and alternative therapies A mental status examina-tion and screening for depression and anxiety should follow.The Beck Depression Inventory or SIG-E-CAPS mnemonic (Sleep,Interest, Guilt, Energy, Concentration, Appetite, Psychomotorretardation, Suicidal) are useful screening tools The challengewith the diagnostic workup for fatigue is that most laboratory tests

psy-do not yield a significant diagnosis Repeated studies show thatonly about 15% of patients in primary care settings will have anorganic cause for their fatigue (Harrison, Ponka), and laboratory re-sults affect management in as little as 5% of patients (Rosenthal).The following recommendations for the laboratory investiga-tion 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,thyroid function tests, urinalysis

• Clues from the history and examination may indicate theneed for erythrocyte sedimentation rate, monospot, antinu-clear antigen testing, or chest radiography

Differential Diagnosis

The common causes of fatigue are represented in the mnemonic

as lifestyle, anxiety and anemia are among the most commoncauses of fatigue Diabetes and other endocrine disorders, includ-ing thyroid disease, should be considered, as well as an undiscov-ered tumor Many infections, especially those of viral origin, causefatigue, as well as insomnia and sleep disorders such as obstructivesleep apnea Rheumatologic disorders, such as rheumatoid arthri-tis, systemic lupus erythematosus, and fibromyalgia, are often ac-companied by fatigue Endocarditis, while rare, is a must-not-missdiagnosis, as are other cardiac conditions such as coronary artery

Box 1 Common Causes of Fatigue: DEAD TIRED

disease Finally, drugs, either prescription or of personal use or

abuse, should be considered

Chronic Fatigue Syndrome is a specific clinical diagnosis

char-acterized by unexplained, persistent or relapsing fatigue, not

re-lieved by rest, that substantially limits daily activity In addition,

there must be at least four of the following: memory or

concentra-tion impairment, sore throat, tender cervical or axillary lymph

nodes, muscle pain, multijoint pain without swelling or

tender-ness, 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

nat-ural course and most frequent causes of fatigue Any underlying

cause discovered in the history, examination, or laboratory

evalu-ation should be treated If depression, anxiety, or environmental

stress is suspected, early assessment and treatment is important

In fatigue that remains unexplained, 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

ther-apy, 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 1961;4:561.

Gialamas A, Beilby JJ, Pratt NL, et al Investigating tiredness in Australian general

practice Aust Fam Physician 2003;32:663.

Harrison M Pathology testing in the tired patient: a rational approach Aust Fam

Sharpe M, Wilks D Fatigue BMJ 2002;325:480.

Viner RM, Clark C, Taylor SJ, et al Longitudinal risk factors for persistent fatigue in

adolescents Arch Pediatr Adolesc Med 2008;162:469.

FEVER

Method of

Ann M Aring, MD

CURRENT DIAGNOSIS

• The definition of fever is arbitrary, because temperature varies

with fever

• Temperature accuracy depends on the measurement

tech-nique Oral temperatures are preferred in patients older than

5 years Rectal temperatures are preferred in infants

• Fever in infants younger than 3 months or in neutropenic

patients is considered a medical emergency that warrants

immediate further evaluation

• Fever is beneficial but is associated with increased cardiac mand and increased metabolic needs Benign febrile seizurescan occur in young children with a fever

de-• Fever of unknown origin (FUO) in children merits a thoroughevaluation based on the age of the child FUO in adults is de-

3 weeks’ duration and whose cause remains undiagnosed after

3 days in the hospital or after three outpatient visits

• Hyperthermia is characterized by a temperature above the

CURRENT THERAPY

• Antipyretic therapy for children includes acetaminophen 10 to

15 mg/kg every 4 to 6 hours for children older than 3 months oribuprofen 10 mg/kg every 6 hours for children older than

6 months

• Antipyretic therapy for adults and adolescents includes aminophen 650 mg to 1000 mg every 6 hours to a maximum

acet-of 4000 mg per day, or ibupracet-ofen 200 to 400 mg every 6 hours

• Aspirin (salicylic acid) should not be used in children due to therisk of Reye’s syndrome In adults, the dose is 325 to 650 mgevery 6 hours as needed for fever

• Combining two antipyretics for fever, such as ibuprofen andacetaminophen, has not been proved to produce quicker orlonger-lasting responses

• Sponge bathing should be done with tepid water and noalcohol

Patients often come to the physician’s office with a fever Fever can

be present in a wide variety of clinical presentations ranging fromself-limited viral illnesses to serious bacterial infections Most fe-brile conditions can be easily diagnosed with other presentingsymptoms and a problem-focused physical examination How-ever, fever produces anxiety for patients, parents, and health careproviders, which can lead to overtreatment Typically, fever istransient and only requires treatment to provide patient comfort

Definitions

The definition of fever is arbitrary, because temperature variesdaily within individual persons The hypothalamic thermostat

body temperature varies in a regular pattern each day This dian temperature rhythm, or diurnal variation, results in lowerbody temperatures in the early morning and temperatures approx-

The word fever is derived from the Latin fovere (to warm) Inadults and children older than 12 years, fever is generally accepted

The methods of determining body temperature are oral, rectal,and axillary The oral route of determining temperature is pre-ferred in children older than 5 years and in adults Typically, rectaltemperatures are obtained in infants by placing a lubricated ther-mometer in the rectum In general, axillary temperatures are inac-curate and should not be used Liquid crystal strips applied to theforehead and temperature-sensitive pacifiers are popular withparents but are inaccurate and miss fevers in many children

The temperature considered to be the physiologic limit to

temperature higher than this hypothalamic set point mia is due to an interference within the normal mechanisms thatbalance heat production and dissipation or an insult to thehypothalamus

11

When the cause of a fever is unknown, two terms may be used:

fever of unknown origin (FUO) and fever of unknown source The

definition of FUO in adults includes a temperature higher than

re-mains undiagnosed after 3 days in the hospital or after three

out-patient visits FUO is also used to define a fever that occurs at

different periods over weeks or months Fever of unknown source

is defined as a fever in the first week of an illness

Pathogenesis and Physiology

Fever is a physiologic mechanism that occurs when an inciting

stimulus causes an inflammatory response Fever may be caused

by infections, vaccines, tissue injury, malignancy, drugs, collagen

vascular diseases, granulomatous disease, inflammatory bowel

dis-ease, endocrine disorders such as thyrotoxicosis and

pheochromo-cytoma, and central nervous system abnormalities Dehydration,

increased physical activity, and heat exposure can all cause an

elevation in temperature Infections cause most fevers in all age

groups

Monocytes or tissue macrophages are activated by the microbial

or nonmicrobial stimuli to produce various cytokines with

pyro-genic activity The list of currently recognized pyropyro-genic cytokines

includes interleukin-1 (IL-1), tumor necrosis factor a (TNF-a), IL-6,

interferon-b (IFN-b), and interferon-g (IFN-g) These cytokines

activate the arachadonic acid cascade and increase production of

set point in the hypothalamus at a higher level

Thermoregulatory responses include redirecting blood to or

from cutaneous vascular beds, increased or decreased sweating,

and behavioral responses such as seeking warmer or cooler

envi-ronmental temperatures The body dissipates heat via evaporation

of water from the body surface and lungs through radiation

(60%), convection (12%), and conduction (3%)

Risks and Benefits of Fever

Fever is beneficial and not usually harmful to the host, with a few

exceptions Fever is associated with increased cardiac demand and

increased metabolic needs In pregnancy, fever is associated with

harmful clinical effects Many animal studies have shown that

fe-ver enhances the immunologic response to infectious agents Use

of antipyretic medications to lower fever increases both morbidity

and mortality in infected laboratory animals and prolongs

vari-cella infections in humans

Febrile seizures are usually benign but can cause considerable

parental anxiety Febrile seizures are divided into two types: simple

and complex (prolonged, recur more than once in 24 hours, or are

focal) Recent studies have shown that in previously normal

chil-dren, most simple febrile seizures are not associated with recurrent

seizures or brain damage

Fever of Unknown Origin

Adults

The evaluation of FUO remains among the most challenging

prob-lems facing the clinician There are four categories Classic FUO is

commonly caused by infections, drug fever, malignancy, and

in periodontal and perianal infections; candidemia and aspergillosis

are major causes Nosocomial FUO is commonly caused by septic

thrombophlebitis, drug fever, and Clostridium difficile colitis In

HIV-associated FUO, Mycobacterium avium complex infections,

tuberculosis, non-Hodgkin’s lymphoma, cytomegalovirus, and drug

fever are important etiologies

Children

Febrile illness in infants and young children is common A

com-plete history and physical examination, including vital signs, skin

color and exanthems, behavior state, and hydration status, do not

reveal a source of infection in 20% of febrile children The child’s

age determines the need for further investigation Febrile infants

younger than 28 days should have a complete blood count(CBC) with differential; electrolytes; serum glucose; cerebrospinalfluid (CSF) Gram stain and cell count; cultures from blood, CSF,and urine; group B streptococcal antigen from urine and CSF;and a chest x-ray Management requires hospitalization and em-piric parenteral antibiotics

For children 28 to 90 days old, obtain a CBC with differentialand urinalysis with culture A low-risk child is defined as a pre-viously healthy term infant who has no focal bacterial infection

on examination If the white blood cell count (WBC) is greater

as CSF Gram stain, culture, cell count, glucose, and protein.For a positive CSF Gram stain or abnormal CSF count, the pa-tient should be admitted and parenteral antibiotics should begiven For negative CSF Gram stain, normal CSF cell count,and negative urinalysis, the child should be given ceftriaxone(Rocephin) 50 mg/kg (maximum dose, 1 g) and reevaluated in

24 hours For a positive urinalysis or urine culture, the patientmay be given oral antibiotics as an outpatient and reexamined

in 24 hours If the child cannot take oral antibiotics, he or shemust be admitted for parenteral antibiotics For a WBC less than

child may be followed closely as an outpatient The child should

be reevaluated in 24 hours High-risk infants are toxic appearingwith lethargy, signs of poor perfusion, hypoventilation, hyperven-tilation, or cyanosis High-risk infants need to be admitted to thehospital with parental antibiotics

For children 3 to 36 months old who have a fever without asource, no diagnostic tests or antibiotics are needed if the child

Acetaminophen (Tylenol) 10 mg/kg may be given with tions to give every 6 hours as needed The child’s caregiver shouldalso be instructed to return to the clinician if the fever persistslonger than 48 hours or if the patient’s condition worsens If

differ-ential In addition, a boy younger than 6 months or a girl youngerthan 2 years should have a urine culture Blood cultures are indi-

of sepsis or meningitis is suspected based on history, observation,and physical examination Empiric antibiotic therapy with ceftri-axone 50 mg/kg (maximum dose, 1 g) should be given if the tem-

High-risk children in this age group should be admitted to the hospitalfor broad-spectrum parenteral antibiotics

Treatment

Antipyretic medications are commonly used for the symptomaticrelief of fever Acetaminophen, ibuprofen (Advil, Motrin), and as-pirin are inhibitors of hypothalamic cyclooxygenase, thus inhibit-

agents Ibuprofen and aspirin are also antiinflammatory agents;acetaminophen does not have any antiinflammatory properties.Acetaminophen is available in a wide variety of dosage formsincluding drops, elixir, syrup, capsule, tablet, chewable tablet,and suppository Dosing is generally 10 to 15 mg/kg every 4 to

6 hours in children older than 3 months For adults, phen dosing is 650 to 1000 mg every 6 hours Maximum dailydose of acetaminophen is 75 mg/kg (or 720 mg) in children and

acetamino-4000 mg in adolescents and adults

Ibuprofen is a nonsteroidal antiinflammatory (NSAID) drugthat may be given to febrile children 6 months or older Ibuprofen

is quickly absorbed and produces a more rapid temperature falland longer duration of action than acetaminophen This advan-tage might not be maintained after the first dose is given Dosing

in children is 10 mg/kg every 6 to 8 hours Adults and adolescentsmay take doses of 200 to 400 mg every 6 hours Ibuprofen is alsoavailable in a wide variety of dosage forms including drops, elixir,syrup, capsule, tablet, and chewable tablet

Aspirin (salicylic acid) remains an effective treatment for fever

in adults Because aspirin is associated with Reye’s syndrome in

children, aspirin is not recommended for treating fever in

chil-dren Adult dosing is 325 to 650 mg every 4 to 6 hours as

needed

Combining two antipyretics for fever, such as ibuprofen and

acetaminophen, is common clinical practice Combinations have

not been proved to produce quicker or longer-lasting responses

The American Academy of Pediatrics (AAP) cautions against using

multiple antipyretics because of an increase in the likelihood of

dosing errors Combining drugs is more expensive and could also

delay proper diagnosis or therapy

Nonpharmacologic treatment can also provide relief from the

discomfort of fever Extra oral fluids should be encouraged to

pre-vent dehydration Sponge bathing with tepid water may be used

Alcohol or ice water should not be used for sponge bathing

Alco-hol is absorbed through the skin and can cause hypoglycemia or

dehydration Both alcohol and ice water increase shivering and

can cause more discomfort

References

Aronoff DM, Neilson EG Antipyretics: Mechanisms of action and clinical use in

fever suppression Am J Med 2001;111(4):304–15.

Baraff LJ Management of fever without source in infants and children Ann Emerg

Med 2000;36:602–14.

Crocetti M, Moghbeli N, Serwint J Fever phobia revisited: Have parental

misconcep-tions about fever changed in 20 years? Pediatrics 2001;107(6):1241–6.

Finkelstein JA Fever in pediatric primary care: Occurrence, management, and

out-comes Pediatrics 2000;105:260–6.

Greisman LA, Mackowiak PA Fever: Beneficial and detrimental effects of

antipy-retics Curr Opin Infect Dis 2002;15(3):241–5.

Kourtis AP, Sullivan DT, Sathian U Practice guidelines for the management of febrile

infants less than 90 days of age at the ambulatory network of a large pediatric

health care system in the United States: Summary of new evidence Clin Pediatr

2004;43(1):11–6.

Knockaert DC, Vanderschueren S, Blockmans D Fever of unknown origin in adults:

40 years on J Intern Med 2003;253:263–75.

Mackowiak PA Temperature regulation and the pathogenesis of fever In:

Mandell GL, Bennett JE, Donlin R, editors Principles and Practices of Infection

Diseases, Vol 1 Philadelphia: Churchill Livingstone; 2000 p 604–22.

McCarthy PL Fever without apparent source on clinical examination Curr Opin

Pediatr 2004;16(1):94–106.

Mourad O, Palda V, Detsky A A comprehensive evidence-based approach to fever of

unknown origin Arch Intern Med 2003;163:545–51.

Roth AR, Basello GM Approach to the adult patient with fever of unknown origin.

Am Fam Phys 2003;68(11):2223–8.

HEADACHE

Method of

R Michael Gallagher, DO

Headache is a disturbing and sometimes fearsome affliction that

has plagued humankind throughout recorded history It often is

debilitating and particularly disturbing to the sufferer because

the pain is located in the head, the very center of the body’s

cog-nitive and control functions With its accompanying pain and

de-bilitating symptoms, stress can mount and the headache can

become all consuming

Headache is experienced by all age groups from young children

to the elderly It is more common than asthma, diabetes, mental

illness, and rheumatoid arthritis In fact, the World Health

Orga-nization identifies severe migraine, along with psychosis and

quad-riplegia, as “one of the most debilitating chronic conditions.”

Although the majority of Americans experience tension-type

head-aches at some time in their lives, approximately 30 million

expe-rience migraine headache: 13% of women and 6% of men,

predominantly in their most productive years between the ages

of 13 and 55 years Prepubescent boys and girls suffer equally;

however, boys often outgrow their migraine attacks as they

ma-ture, and they are less subjected to hormonal influences Smaller

percentages of people, by comparison, suffer with other chronic

headaches, such as cluster headache and chronic daily headache

No sure diagnostic tests are available to differentiate headachetypes The headache condition can progress over time in fre-quency, severity, and debilitation Each sufferer can be differentand may require a detailed evaluation and individualized treat-ment plan; more frequent or prolonged attacks often necessitate

a more comprehensive treatment plan Thus, the headache lem can be a challenge for both the sufferer and the clinician

prob-During the 20th century, dramatic advancements were made inmedicine Longevity and quality of life improved for many individ-uals Unfortunately, for headache sufferers, most of these advanceswere for maladies that killed or maimed rather than for non–life-threatening conditions It was not until the 1960s that even areasonable preventive medication, propranolol (Inderal), wasintroduced, and by the 1980s only a handful of medications wereavailable for wide use Physicians had to improvise with medica-tions and treatments that were originally designated for othermedical conditions

In the late 1980s and 1990s, epidemiologic, psychosocial, andpharmacologic research resulted in an increase in available head-ache information and treatment possibilities The development ofthe triptans, serotonin agonists, brought a new awareness to bothphysicians and sufferers Today, seven triptans and two relativelynew preventive medications are available In spite of this, a minor-ity of migraine sufferers use these options, and more than 50%

continue to self-treat without benefit of professional care

In the past, patients wanted the physician to believe their ache problem was real They hoped that they would be takenseriously and that the physician would make a sincere attempt

head-to help them The headache patient has changed The headachesufferer who seeks treatment today is more knowledgeable andinterested in rapid relief and tolerability of medication

Evaluation and Diagnosis

An accurate diagnosis is essential for effective management ofpatients with the more commonly encountered headaches Be-cause no biologic markers or diagnostic tests exist to determineheadache type, the history is the single most important element

in the evaluation of the headache patient Various headache typessometimes have similar initial presentations, or patients may sufferwith more than one type of headache (e.g., migraine and tension-type headache), which can be confusing at first, but the careful his-tory usually differentiates the headache type In general, little inthe way of diagnostic testing is needed unless a physical cause issuspected Some physicians prefer to perform simple laboratorytests to establish a baseline for medication toleration and monitor-

The headache complaint on occasion can be a sign of a more rious medical condition, such as a tumor, infection, or aneurysm

se-For this reason, the clinician always must be cautious and diligent

in establishing an accurate and timely diagnosis Certain so-calledred flags in the history require immediate attention These includeany complex of symptoms or history that does not fit a typicalheadache type; report of a significant neurologic deficit; significant

or prolonged neurologic deficit with aura; late-onset migraine(patient older than 30 years); sudden onset of a new head painwithout history of similar headaches; changes in headache charac-ter; headache associated with elevated temperature; or completelyunresponsive attacks in the absence of analgesic or caffeine over-use When any of these symptoms are present or physical exami-nation reveals significant findings, further diagnostic evaluationwith imaging studies and consultation is imperative

The appropriate headache patient evaluation includes a ough history, physical examination with special attention to thehead and the neurologic, cardiovascular, and musculoskeletal sys-tems, and diagnostic tests when appropriate The history shouldinclude headache onset, location, pain character (e.g., pressure,throb), frequency, duration, associated symptoms, aura or pro-drome, triggers, previous treatment, and family history Certainclues in the history may lean toward the diagnosis of migraine,such as motion sickness, absence of headache during pregnancy,

13

and headache relationship to menses, sun glare, oversleep, fatigue,

fasting, foods, or alcohol

Various diagnostic screening questionnaires and tools have been

developed over the years to assist busy clinicians in establishing the

diagnosis of migraine Most are long and cumbersome and do not

easily become a part of routine patient evaluation A simple

three-question screener for migraine is helpful for generalist clinicians

A “yes” answer to all three questions indicates a strong possibility

of the migraine diagnosis:

1 Do you experience headaches severe enough to see a physician?

2 Are your headaches accompanied by other symptoms?

3 Are your headaches intermittent (i.e., nondaily)?

Note: This screener should not be substituted for a complete

history; it should be used only for screening purposes

Tension-Type Headache

Tension-type headache (TTHA) is the most common of headaches

and first was believed to be caused by sustained muscle contraction

of the neck, jaw, scalp, or facial muscles However, it is now

thought that the sustained muscle contraction can, in fact, be an

epiphenomenon to possible central disturbances rather than a

pri-mary process Evidence suggests that altered levels of serotonin,

substance P, and neuropeptide Y in the serum or platelets of

patients with TTHA are responsible

TTHA is characterized by intermittent or persisting bilateral

pain, usually described as a squeezing pressure or a bandlike

sensation around the head Most patients experience their

symptoms in the frontal, temporal, or occipital areas of the head

Location frequently varies with the attack, and tightness of

the neck and shoulders is common Intensity varies greatly

The attacks can last from hours to days, and in some extreme

cases they may last for months Aura, nausea, photophobia

and phonophobia, and incapacitation are not typically

asso-ciated with TTHA

Many TTHA sufferers easily recognize the origin of their

at-tacks TTHA typically results from emotional upset, periods of

stress, and major life changes Anxiousness, poor adaptation

skills, and anxiety and depression often are present Physical

causes, such as degenerative joint disease, trauma to the head

or neck, poor posture, or temporomandibular joint dysfunction,

also can precipitate attacks Persons older than 50 years are prone

to excessive muscle contraction because of arthritis of the neck

and jaw, poor posture, or stress TTHA that is consistently

precipitated by tension or pathology of the neck frequently is ferred to as a cervicogenic headache In contrast to migraine head-ache, TTHA is more likely to begin in later life

re-Migraine Headache

Migraine headache is a familial disease characterized by unilateral

or bilateral paroxysmal headache lasting hours to days Adultwomen experience attacks more than men by a ratio of 3:1 Chil-dren and the elderly experience migraine equally Attacks occurfrom as infrequently as one or two per year to several times weekly.Associated symptoms usually occur and frequently include throb-bing, nausea, vomiting, photophobia, phonophobia, fluid reten-tion, and mood changes

The two basic types of migraine headache are migraine withaura (previously called classic migraine) and migraine withoutaura (previously called common migraine) Migraine with aura

is preceded by an aura, a transient neurologic symptom that ally is visual, such as scotoma, teichopsia, tunnel vision, or visualfield deficit, lasting 10 to 30 minutes However, aura can manifest

usu-as any neurological deficit Migraine without aura is more monly experienced and comes on gradually or is present on awak-ening from sleep In some patients, these headaches are associatedwith a nonspecific prolonged prodrome, such as mood changes,food cravings, or fluid retention hours before the pain

com-The underlying cause of migraine headache is not clearly lished, and various theories are proposed Migraine appears to be

estab-of genetic origin and to be an inflammatory disease that causes turbances in serotonin use and activity Strong evidence indicatesthe migrainous attack originates in the central nervous system bystimulation of the locus ceruleus and dorsal raphe nuclei Resul-tant changes alter cerebral and extracranial blood flow, activatethe trigeminovascular system, and cause vascular dilation, neuro-genic inflammation, and pain Various precipitants are known,and many sufferers report that migraine attacks frequently are as-sociated with menstruation or are triggered by foods containingvasoactive amines, strong odors, too much or too little sleep,sun glare, stress, altitude, weather changes, exertion, or fasting(Boxes 1and2,Table 2)

dis-Some physicians classify migraine according to its precipitant ordescription (e.g., menstrual migraine, exertional migraine, coitalmigraine, cervicogenic migraine, cyclic migraine, acephalic mi-graine) Regardless, the fundamentals of evaluation and treatmentare the same

Cluster Headache

The cause of cluster headache is unknown, and little credible search is available Various possibilities or theories are suggestedand include, but are not limited to, disturbances in histamine pro-duction or use; hypothalamic biorhythm dysfunction; or serotoninand neurotransmitter mechanisms similar to those of migraine.Some authorities consider cluster headache one of the most severepain conditions known to humankind

re-TABLE 1 Current Diagnosis

Tension-Type Headache

Bilateral variable pain Variable Hours to days

Squeezing or bandlike Often related to

known precipitant Tightness of head and

shoulders

Migraine Headache

Throbbing or constant pain Sometimes cyclic

Unilateral severe boring pain Multiple daily 45–90 min

Ipsilateral lacrimation, scleral

injection, rhinorrhea

Near-daily Cycles of

attacks Eyelid droop

Restlessness

Box 1 Migraine Dietary Triggers

• Dairy: Ripened cheese (cheddar, brie, camembert, half-cup ofsour cream)

• Meats: Processed lunch meats, hot dogs, sausage, bologna,salami, chicken liver

• Fish: Pickled or dried herring

• Grains: Sourdough bread

• Fruits: Bananas, raisins, figs, avocado, half-cup limit of citrus

• Vegetables: Broad and fava beans, onions, snow peas

• Other: Chocolate, nuts, peanut butter, pickled foods, Chinesefood with monosodium glutamate (MSG)

• Beverages: Most wines and alcohol, 200-mg daily limit ofcaffeine

• Additives: MSG, soy sauce, meat tenderizers, aspartame,sulfites, garlic

Cluster headache predominantly affects men, with a

male-to-female ratio of 6:1 It occurs in well under 0.5% of the population

Onset later in life (after age 30 years) is common, and patients

sometimes report head injury or a traumatic event occurring

months before onset Attacks occur on a daily or near-daily basis

for weeks or months at a time and mysteriously disappear for

months to years regardless of treatment, only to recur and cycle

again Although nonspecialist physicians only occasionally

en-counter the patient with cluster headaches, it is important to

con-sider cluster headaches in the differential diagnosis

The typical patient with a cluster headache experiences

rela-tively brief attacks (45–90 minutes) of horrible unilateral head

pain associated with ipsilateral lacrimation, scleral injection,

rhi-norrhea, or eyelid droop The hallmark of the syndrome is its

as-sociated symptoms and its severe and intense pain During attacks,

most cluster patients move about, trying unsuccessfully to get

more comfortable, similar to renal colic, in contrast to migraine

sufferers, who prefer to lie quietly in a dark quiet room Few gers are identified, and alcohol almost always precipitates anattack during a cluster “on” cycle A rare form of cluster headache,chronic cluster, does not cycle and continues on a daily or near-daily basis without cessation

trig-Treatment

The doctor–patient relationship frequently is the key to successfultreatment in the headache patient Although to some this state-ment seems an obvious truism, its importance cannot be overem-phasized Patients who experience frequent, near-daily, or dailyheadaches invariably require a comprehensive treatment programthat necessitates good communication Anxious patients some-times do not comprehend medical explanations or instructions;

busy doctors sometimes do not have or take the time to ensure thatthe patient understands

The two elements of headache treatment are abortive treatment,directed at attacks once they have begun, and prophylactic treat-ment, directed at preventing or reducing the frequency of attacks

In general, the abortive approach is used for patients who sufferinfrequent attacks and for those who experience breakthroughattacks while undergoing prophylactic therapy Prophylactic ther-apy should be instituted when headaches are frequent, when head-aches are unresponsive to abortive medication, or when there are

Headache treatment can include nonpharmacologic measures,such as physical exercise, stretching, stress avoidance, relaxationexercises, biofeedback, manipulation, massage, or cold/warmpacks Pharmacologic therapies can include a vast array of medi-caments from over-the-counter (OTC) drugs to prescription drugssuch as triptans, other vasoconstrictors, b-blockers, antiepilepticagents, antidepressants, nonsteroidal antiinflammatory drugs(NSAIDs), analgesics, muscle relaxants, anxiolytics, and others

Treatment, whether prophylactic or abortive, should follow adefinite plan incorporating the clinician and patient into a teamfocused on reducing the headache frequency, severity, and disabil-ity As mentioned earlier, impressions and physical findings should

be explained to the patient in as much detail as necessary to ensurethe patient’s complete understanding The complexity of the head-ache condition needs to be explained, emphasizing its chronicity,rather than its curability, and that the goal of treatment is diseasecontrol

The comprehensiveness of the treatment plan depends on thefrequency of the patient’s attacks The more frequent and severethe attacks, the more detailed plan may be necessary Patientsexperiencing infrequent attacks (e.g., once or twice monthly)may require only an abortive medication and little else Patientswith more frequent attacks may benefit from dietary restrictions,psychosocial intervention, biofeedback relaxation training, ma-nipulation, and physical modality intervention, in addition tomedication

Tension-Type Headache Treatment

TTHA often is associated with emotional stress and muscle strain

or tension of the shoulders and neck Simple self-administeredmeasures, such as stress avoidance, stretching, warm packs, or re-laxation techniques, can be helpful in reducing or relieving at-tacks More comprehensive professional intervention, such asmanipulation, physical therapy, local injections, or biofeedbacktraining, are considerations for more frequent or severe cases

Prophylactically, the use of OTC or prescription medicationscan be considered in addition to nonmedicinal measures for reduc-ing the frequency and duration of attacks NSAIDs, muscle relax-ants, or antidepressants (tricyclic antidepressant [TCA], selectiveserotonin reuptake inhibitor [SSRI]), at the lowest effective doses,are more commonly used

Box 2 Migraine Triggers

Stretching Muscle relaxants

Warm packs Combination analgesics

Relaxation techniques NSAIDs Muscle relaxants Antidepressants

blockers Dihydroergotamine

Divalproex sodium Ergotamine

NSAIDs Lithium Steroids

*FDA indication.

Abbreviations: NSAID ¼ nonsteroidal antiinflammatory drug; OTC ¼

over-the-counter; TCA ¼ tricyclic antidepressant.

1 Not FDA approved for this indication.

15

patient over a 2- to 3-week period, can be an effective preventative.

low doses at night over 1 to 3 months, are frequently effective,

es-pecially in patients with anxiety or mild depression The SSRI drugs,

doses, with a similar mechanism to the TCAs, can be administered

at night for limited periods Other muscle relaxants occasionally

can be effective Potential side effects can limit the use of NSAIDs

(gastrointestinal irritation) and the TCAs (fatigue and weight gain)

Abortive or symptomatic treatment of TTHA can include

sim-ple OTC medications (e.g., aspirin or acetaminophen), NSAIDs

(shortacting), muscle relaxants, combination analgesics, and, in

some cases, opioid or opioidlike drugs Caution should be

exer-cised in prescribing potentially habituating drugs Daily or

near-daily use of analgesics can lead to analgesic rebound headache,

Medication Overuse Headache, which can compound the patient’s

headache problem

tension-type and migraine headache, but controlled studies are

limited In this treatment, a diluted solution of botulism toxin is

injected into various muscles of the face, scalp, neck, or shoulders

Because this treatment frequently is used in headache specialty and

pain centers, simultaneous comprehensive measures and

medica-tion may contribute to positive results Side effects from botulism

toxin are low when injected properly

Migraine Treatment

Migraineurs are unique individuals, and the effectiveness and

tol-erance of medications can vary from patient to patient

Medica-tion changes, combinaMedica-tions of medicaMedica-tions, and trial and error

may be necessary in the early stages of treatment

Nonmedicinal measures for migraine sufferers include

biofeed-back stress reduction, caffeine and dietary restrictions,

regimenta-tion of meals and sleep, rest, exercise, stretching, and avoidance

of work or activity overload Limiting caffeine to less than

200 mg/day is important to prevent the caffeine headache (rebound

headache) in most patients Elimination of vasoactive foods, such as

chocolate, aged cheese, and processed meats, and avoidance of

fast-ing for more than 4 hours can be helpful for patients with more

relaxation, regular sleep schedules, and following a healthy lifestyle

are frequently included in a comprehensive treatment regimen In

some patients, especially children and adolescents, biofeedback

stress reduction or psychotherapeutic intervention may be necessary

The more commonly used medications for prophylaxis are

b-blockers, calcium channel blockers, antiepileptics

(neurostabi-lizers), and the antidepressants Treatment should be continued

for a 4- to 8-week trial before discontinuation for ineffectiveness.Determination of which medication to use depends on com-orbidities, interactions with concomitant medications, andtolerability

b-Blockers such as propranolol (Inderal) and timolol dren) are nonselective and are approved by the Food and DrugAdministration (FDA) for migraine prevention Other b-blockers,

in migraine is not wholly understood, but it is thought to involveanxiolytic effects as well as vascular changes and stabilization Theusual dosage is recommended (e.g., timolol 10–30 mg/day, pro-pranolol 120–160 mg/day), and many consider the nighttime dosethe more significant

Calcium channel antagonists are well tolerated in general and can

be as effective as the b-blockers They are believed to alter serotoninrelease and inhibit platelet serotonin uptake and release within the

commonly recommended to patients Dosage can vary from 120

is rarely used in the United States because of its high cost

preven-tion over the years, with mixed results Their use is now limitedwith the advent of newer, more easily tolerated agents, such asdivalproex sodium (Depakote) and topiramate (Topamax).Divalproex sodium is effective in reducing migraine attacks and

is particularly useful in patients with coexisting head injury, zure disorders, and bipolar disorders It is thought to improve in-hibitory and excitatory amino acid imbalance in the brain It isbest to start with a lower dose and to gradually increase as neededand tolerated The dosage of 500 to 1000 mg/day is more fre-quently prescribed A commonly experienced side effect is seda-tion, which can sometimes be used to the patient’s advantagewhen anxiolytic effects are needed

sei-Topiramate is the most recent preventive medication approved

by the FDA for migraine prophylaxis It has multiple mechanisms

of action, but its exact mechanism in migraine headache is known Its effectiveness is believed to involve sodium ion channelstabilization, calcium ion channels, GABA (g-aminobutyric acid)receptors, and neuronal membrane stabilization The averagedaily dose is variable and ranges from 30 to 100 mg/day A mostunusual side effect of weight loss or appetite suppression can beused to the patient’s advantage in preventing weight gain, whichfrequently accompanies migraine prophylactic medications.The TCAs can be useful in patients who experience frequent at-tacks and in those who experience anxiety and depression TheTCAs inhibit synaptic reuptake of serotonin, thereby reducingneuron firing and release of neurotransmitters Starting with alow dose in the evening and titrating up to efficacy and tolerability

un-is recommended Significant anticholinergic and sedation effects

patients, but their use in migraine prevention is limited

In general, prophylactic medications should be taken for 6 to

8 weeks to determine efficacy If effective, a course of 4 to 6 months

is recommended before an attempt is made to discontinuemedication

A variety of abortive treatment options are available for migraine

in-terest and are frequently prescribed, other medications continue to

be used, including ergotamine and its derivatives, isometheptene,and NSAIDs Many of the abortive medications carry significantprescribing limitations that must be taken into consideration Vaso-constrictor medications are contraindicated in patients with cardio-vascular or peripheral vascular disease NSAIDs should not be used

in those with gastrointestinal or bleeding disorders As with allmedications, the clinician must consider appropriate prescribing,contraindications, and side-effect information

1 Not FDA approved for this indication.

TABLE 3 Triptans

MEDICATION BRANDNAME HALF-LIFE FORM/STRENGTH

Sumatriptan Imitrex 1.5 hr Oral: 25, 50, 100 mg;

NS: 20 mg;

injection: 6 mg, 4 mg

Zolmitriptan Zomig 3 hr Oral: 2.5, 5 mg; Melt:

2.5, 5 mg; NS: 5 mg Rizatriptan Maxalt 2–3 hr Oral: 5, 10 mg; Melt:

10 mg

Abbreviations: Melt ¼ oral disintegrating; NS ¼ nasal steroid 1

Not FDA approved for this indication.