Hand-Foot-and-Mouth Disease

  • Author: Stephen J Nervi, MD; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Aug 15, 2016
 

Practice Essentials

Hand-foot-and-mouth disease (HFMD) is an acute viral illness that presents as a vesicular eruption in the mouth (see the image below), but it can also involve the hands, feet, buttocks, and/or genitalia. Coxsackievirus A type 16 (CVA16) 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 caused outbreaks of HFMD with associated neurologic involvement in the western Pacific region.

The lower lip has an ulcer with an erythematous ha The lower lip has an ulcer with an erythematous halo.

See Clues in the Oral Cavity: Are You Missing the Diagnosis?, a Critical Images slideshow, to help identify the causes of abnormalities of the oral cavity.

Also, see the 15 Rashes You Need to Know: Common Dermatologic Diagnoses slideshow to help identify and treat various rashes and the 15 Back-to-School Illnesses You Should Know slideshow to help identify conditions that may occur in young patients after they return to the classroom.

Signs and symptoms

The history in patients with HFMD is as follows:

  • Sore mouth or throat
  • Malaise
  • Rarely, vomiting occurs in HFMD cases caused by EV-71

Physical findings include the following:

  • Initially, macular lesions appear on the buccal mucosa, tongue, and/or hard palate
  • These mucosal lesions rapidly progress to vesicles that erode and become surrounded by an erythematous halo
  • Lesions may also be found on the hands, feet, buttocks, and genitalia
  • A fever of 38-39°C may be present for 24-48 hours

Atypical clinical features include concomitant aseptic meningitis in HFMD caused by coxsackievirus strains (rare).[1] HFMD caused by EV-71 has a higher incidence of neurologic involvement, including the following[2] :

  • A poliolike syndrome
  • Aseptic meningitis
  • Encephalitis
  • Encephalomyelitis
  • Acute cerebellar ataxia
  • Acute transverse myelitis
  • Guillain-Barré syndrome
  • Opsomyoclonus syndrome
  • Benign intracranial hypertension

See Clinical Presentation for more detail.

Diagnosis

The diagnosis of HFMD is typically based on clinical grounds. Laboratory studies are usually unnecessary, but the following may be done:

  • The virus can be isolated and identified via culture and immunoassay from cutaneous lesions, mucosal lesions, or stool samples; oral specimens have the highest isolation rate
  • In patients with vesicles, vesicle swabs are also a good source for viral collection
  • In patients without vesicles, rectal swabs can be collected
  • For viral isolation, 2 swab collections are recommended: From the throat and from either vesicles or the rectum
  • Serologic testing (eg, acute and convalescent antibody levels) may be obtained
  • Differentiating coxsackievirus-associated HFMD from EV-71–associated HFMD may have prognostic significance
  • PCR and microarray technology are among the various ways of identifying the causative virus [3]

See Workup for more detail.

Management

There is no antiviral agent specific for the etiologic agents of HFMD. Instead, the treatment is supportive, as follows:

  • Ensure adequate fluid intake to prevent dehydration; cold liquids are generally preferable
  • Spicy or acidic substances may cause discomfort
  • Intravenous hydration may be necessary if the patient has moderate-to-severe dehydration or if discomfort precludes oral intake
  • Fever may be treated with antipyretics
  • Pain may be treated with standard doses of acetaminophen or ibuprofen
  • Direct analgesia may also be applied to the oral cavity via mouthwashes or sprays
  • IVIG and milrinone have shown some efficacy in a few reports [4, 5, 6]

See Treatment and Medication for more detail.

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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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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.[7]

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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.[1, 8]

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.[9] 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.[2]

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.[10]

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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, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

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

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.

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 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, 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

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

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.

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.

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The lower lip has an ulcer with an erythematous halo.
Table 1. Differential Diagnoses of Hand-Foot-and-Mouth Disease
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



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