Hand-Foot-and-Mouth Disease 

  • Author: Stephen J Nervi, MD; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Jan 11, 2012
 

Background

Hand-foot-and-mouth disease (HFMD) is an acute viral illness that presents as a vesicular eruption in the mouth. HFMD can also involve the hands, feet, buttocks, and/or genitalia. Coxsackievirus A type 16 (CV A16) is the etiologic agent involved in most cases of HFMD, but the illness is also associated with coxsackievirus A5, A7, A9, A10, B2, and B5 strains. Enterovirus 71 (EV-71) has also caused outbreaks of HFMD with associated neurologic involvement in the western Pacific region.

Coxsackievirus is a subgroup of the enteroviruses and is a member of the family Picornaviridae. This family consists of small, nonenveloped, single-stranded RNA viruses.

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Pathophysiology

Infection generally occurs via the fecal-oral route or via contact with skin lesions and oral secretions. Viremia develops, followed by invasion of the skin and mucous membranes. Widespread apoptosis likely results in the characteristic lesion formation.

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Epidemiology

Frequency

United States

Epidemics of HFMD generally occur in the summer to early fall months, although cases can occur sporadically all year.

International

HFMD epidemics associated with EV-71 have been more frequent in Southeast Asia in recent years, including Taiwan (1998) and Singapore (2000). Risk factors in these epidemics include attendance at child care centers, contact with HFMD, large family number, and rural residence.[1]

Mortality/Morbidity

  • HFMD caused by coxsackievirus is generally a mild self-limited illness that resolves in 7-10 days; rarely, HFMD may recur or persist. Serious complications are also rare.
  • Severe oral ulcerations can create painful stomatitis. This may interfere with oral intake and cause dehydration, the most common complication of HFMD. Rarely, aseptic meningitis accompanies coxsackievirus-induced HFMD.
  • HFMD caused by EV-71 has a higher incidence of neurologic involvement, including a poliolike syndrome, aseptic meningitis, encephalitis, encephalomyelitis, acute cerebellar ataxia, acute transverse myelitis, Guillain-Barré syndrome, opsomyoclonus syndrome, and benign intracranial hypertension. These neurological complications have been attributed to either immunopathology or virus-induced damage to gray matter.[2, 3]
  • Rarely, cardiopulmonary complications such as myocarditis, interstitial pneumonitis, and pulmonary edema may occur. Neurologic involvement with sequelae is less likely to occur in patients with HFMD caused by coxsackievirus strains than with HFMD caused by EV-71. Chang et al analyzed the Taiwan HFMD epidemic of 1998 and revealed that 68% of the EV-71 cases were uncomplicated.[4] Thirty-two percent of the cases had complications; 7.3% involved aseptic meningitis, 10% involved encephalitis, 2.3% involved poliolike syndrome, 4.5% involved encephalomyelitis, and 6.8% involved fatal pulmonary edema (7.9% of patients died and 4% of patients had sequelae). In the coxsackievirus A16 group, 94% of the cases of were uncomplicated; only 6.3% cases were complicated by aseptic meningitis; no fatalities or sequelae were reported.
  • Chong et al observed vomiting, leukocytosis, and an absence of mouth ulcers as predictive risk factors for fatal cases of EV-71 HFMD during the Singapore epidemic in 2000.[5]

Sex

Most reports indicate that HFMD has no sexual predilection. Some epidemic data observe a slight male-to-female predominance ratio of 1.2-1.3:1.

Age

Children younger than 10 years are most commonly affected with HFMD, and subsequent outbreaks among family members and close contacts may develop.[6]

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Contributor Information and Disclosures
Author

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, and Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Rajendra Kapila, MD, MBBS  Associate Professor, Department of Medicine, University of Medicine and Dentistry of New Jersey-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, and Infectious Diseases Society of New Jersey

Disclosure: Nothing to disclose.

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.

Specialty Editor Board

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, and New York Academy of Sciences

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

Thomas M Kerkering, MD  Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Thomas M Kerkering, MD 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, Medical Society of Virginia, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Eleftherios Mylonakis, MD  Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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Table 1
IllnessEtiologic AgentUsual Severity of Clinical IllnessAppearance of LesionsLocations of LesionsOther Features
HFMDCoxsackie-virus A16 (most common), A5, A7, A9, A10, B2, B5



Enterovirus 71



MildPapules →



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



HerpanginaCoxsackie-virus A1-A10, A16, A22



Echovirus 3, 6, 9, 16, 17, 25, 30



Moderate; can be severePapules →



Vesicles → ulcerations on an erythematous base



Usually 2-4 mm



Posterior oral cavity



Tonsils, soft palate, uvula



Temperature generally high
Herpetic gingivostomatitisHerpes simplex virus-1Moderate to severeVesicles



ulcerations



Anterior oral cavity



Lips, gingiva, buccal mucosa



Temperature generally high



Lymphadeno-pathy



Aphthous stomatitisUnknownMild to severeUlcerations; larger than in viral enanthemsLips, tongue, buccal mucosa; generally not diffuseAfebrile



May be recurrent



Stevens-Johnson syndromeImmunologicModerate to severeCoalescent vesicles, which then ulcerateLips, gingiva, buccal mucosa, tongue, pharynxTargetlike cutaneous lesions



Diffuse mucous membrane involvement



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