Dermatologic Manifestations of Hand-Foot-and-Mouth Disease

Updated: Apr 14, 2017
  • Author: Brad S Graham, MD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

Hand-foot-and-mouth disease (HFMD) is a viral illness with a distinct clinical presentation of oral and characteristic distal extremity lesions. Most commonly, the etiologic agents are coxsackieviruses, members of the Picornaviridae family.

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Pathophysiology

Epidemic hand-foot-and-mouth disease (HFMD) viral infections are usually caused by members of the Enterovirus genus, most commonly, coxsackievirus A16, A6, or enterovirus 71. In addition, sporadic cases with coxsackievirus types A4-A7, A9, A10, B1-B3, and B5 have been reported. Infections usually occur as isolated events, but epidemics occur regularly. An outbreak of HFMD in China during 2003 was caused by echovirus 19. [1] More widespread involvement resembling eczema herpeticum, systemic involvement, and late-stage onychomadesis are characteristic of the A6 strain.

Large outbreaks of HFMD in China in recent years have shown that increasing numbers of outbreaks are caused predominantly by enterovirus 71 (86.5%), and in part by coxsackievirus A16 (6.9%). The high incidence of mixed infections with enterovirus 71 and coxsackievirus 16 (17.6% of the total coxsackievirus 16–infected cases) has never before been observed in China. [2] A high incidence of mixed infections with enterovirus 71 and coxsackievirus 16 was also observed. [3] Enterovirus 71 infection does not provide immunity to other strains. [4]

The incubation period averages 3-6 days. Coxsackievirus infection is highly contagious. During epidemics, the virus is spread by horizontal transmission from child to child and from mother to fetus. Transmission occurs by means of direct contact with nasal and/or oral secretions, fecal material, or aerosolized droplets in a fecal-oral or oral-oral route. Initial viral implantation in the buccal and ileal mucosa is followed by spread to lymph nodes within 24 hours. Viremia rapidly ensues, with spread to the oral mucosa and skin. By day 7, neutralizing antibody levels increase and the virus is eliminated.

However, a study from China in 2011 showed that the neutralizing antibody response was not correlated with disease severity, suggesting that cellular immune response, besides neutralizing antibodies, could play a critical role in controlling the outcome of enterovirus 71 infection in humans. [5]

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Epidemiology

Frequency

United States

Hand-foot-and-mouth disease (HFMD) epidemics tend to occur every 3 years in the United States.

International

Worldwide HFMD occurrences are reported. A seasonal pattern is present in temperate climates, with a peak incidence in late summer and early fall.

Race

No racial predilection is recognized for hand-foot-and-mouth disease.

Sex

The male-to-female ratio for hand-foot-and-mouth disease is 1:1. Recent large outbreaks of HFMD in China have shown a male-to-female ratio closer to 1.5:1. [6]

Age

Most cases of hand-foot-and-mouth disease affect children younger than 10 years, although cases in adults are reported. Recent large outbreaks of HFMD in China have shown that 95% on infections occur in children younger than 5 years. [6]

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Prognosis

The prognosis for hand-foot-and-mouth disease (HFMD) is excellent; except in large epidemics caused by human enterovirus 71 in which neurologic complications and death have been reported, especially in children.

HFMD is more severe in infants and children than adults, but generally, the disease has a mild course. Coxsackie A6 often presents with more generalized involvement, as well as with more severe systemic symptoms. [7]

Enteroviral infections may also cause myocarditis, epididymitis, pneumonia, meningoencephalitis, and even death. [8] MicroRNA profiles and elevated circulating histones have been used to characterize more severe disease. [9, 10]

Rarely, disease recurs.

Infection in the first trimester may lead to spontaneous abortion or intrauterine growth retardation.

A large outbreak of HFMD in Taiwan caused by enterovirus 71 had a high mortality rate of 19.3% in the severe cases; the deaths resulted from pulmonary hemorrhage. During this outbreak, mortality rates were highest in children younger than 3 years. [11]

In a large epidemic (138 cases) of HFMD related to enterovirus 71 in Singapore, 7 fatalities occurred, most from interstitial pneumonitis or brainstem encephalitis. The report's conclusions were that in general, HFMD is a benign disease but the presence of unusual physical findings, elevated total white blood cell count, and vomiting and the absence of oral ulcers may signify a patient with higher risk of a fatal outcome. [12] Newer reports of large outbreaks of HFMD in China have shown that longer duration of fever, elevated serum C-reactive protein (CRP), and hyperglycemia are risk factors for increased severity of disease. [6]

A later study of an HFMD epidemic (14 children) in Australia, again with enterovirus 71, reported that 9 (64%) developed severe neurologic disease in which the host immune response seemed to cause most of the neurologic manifestations. [13]

In one study of an outbreak HFMD in Sarawak, Malaysia caused by human enterovirus 71, the authors identified 3 clinical risk factors to help detect children at risk for neurologic complications. Total duration of fever for 3 or more days, peak temperature elevation greater or equal to 38.5°C, and a history of lethargy all were independently associated with cerebrospinal fluid pleocytosis and neurologic disease. [14]

In an outbreak in the Republic of Korea with enterovirus 71, duration of fever longer than 4 days, peak temperature elevation greater than 39°C, vomiting, headache, neurologic signs, and serum glucose value over 100 mg/dL were all significant risk factors for neurologic complications. [15]

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Patient Education

The virus that causes hand-foot-and-mouth disease (HFMD) may be present in the patient's stool for 1 month.

The patient’s exclusion from school is generally not required.

Good hand-washing technique is necessary to reduce the potential spread of disease.

To reduce viral spreading, do no rupture blisters.

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