Diagnostic Considerations

There are a large number of disorders to be considered, including ones that include aphthae, such as the rare periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.^[16]

Table 1. Differential Diagnoses of Hand-Foot-and-Mouth Disease (Open Table in a new window)

Illness	Etiologic Agent	Usual Severity of Clinical Illness	Appearance of Lesions	Locations of Lesions	Other Features
HFMD	Coxsackie-virus A16 (most common), A5, A7, A9, A10, B2, B5 Enterovirus 71	Mild	Papules → Vesicles → ulcerations on an erythematous base Usually 2-6 mm	Gingiva Buccal mucosa Tongue Pharynx	Lesions may also be found on hands, feet, buttocks, and genitalia. Low-grade fever
Herpangina	Coxsackie-virus A1-A10, A16, A22 Echovirus 3, 6, 9, 16, 17, 25, 30	Moderate; can be severe	Papules → Vesicles → ulcerations on an erythematous base Usually 2-4 mm	Posterior oral cavity Tonsils, soft palate, uvula	Temperature generally high
Herpetic gingivostomatitis	Herpes simplex virus-1	Moderate to severe	Vesicles ulcerations	Anterior oral cavity Lips, gingiva, buccal mucosa	Temperature generally high Lymphadenopathy
Aphthous stomatitis	Unknown	Mild to severe	Ulcerations; larger than in viral enanthems	Lips, tongue, buccal mucosa; generally not diffuse	Afebrile May be recurrent
Stevens-Johnson syndrome	Immunologic	Moderate to severe	Coalescent vesicles, which then ulcerate	Lips, gingiva, buccal mucosa, tongue, pharynx	Targetlike cutaneous lesions Diffuse mucous membrane involvement

Differential Diagnoses

Workup

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The lower lip has an ulcer with an erythematous halo.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Thomas M Kerkering, MD, FACP, FIDSA Professor of Medicine with Tenure, Division of Infectious Diseases, Virginia Tech Carilion School of Medicine; Adjunct Professor, Department of Population Studies, Masters of Public Health Program, Virginia Tech University, School of Veterinary Medicine

Thomas M Kerkering, MD, FACP, FIDSA is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society for Human and Animal Mycology, Medical Society of Virginia, Roanoke Academy of Medicine, Virginia Infectious Diseases Society, Wilderness Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Gary L Gorby, MD Associate Professor, Departments of Internal Medicine and Medical Microbiology and Immunology, Division of Infectious Diseases, Creighton University School of Medicine; Associate Professor of Medicine, University of Nebraska Medical Center; Associate Chair, Omaha Veterans Affairs Medical Center

Gary L Gorby, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, New York Academy of Sciences

Disclosure: Nothing to disclose.

Rajendra Kapila, MD, MBBS † Professor, Department of Medicine, Rutgers New Jersey Medical School

Rajendra Kapila, MD, MBBS is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey

Disclosure: Nothing to disclose.

Stephen J Nervi, MD Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Stephen J Nervi, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Acknowledgements

Diane H Johnson, MD Assistant Director, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine

Diane H Johnson, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Women's Association, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.