Hand, foot, and mouth disease: Identifying and managing an acute viral syndrome

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ABSTRACTHand, foot, and mouth disease (HFMD) is a common, typically self-limited viral syndrome in children and adults. It is marked by fever, oral ulcers, and skin manifestations affecting the palms, soles, and buttocks, with symptoms usually lasting less than 1 week. Because it has the potential to reach epidemic levels in the United States, general practitioners need to be aware of it.


  • In Asian and Pacific nations, HFMD has been a significant public health concern since 1997, with recurrent epidemics and, in some cases, severe complications, including central nervous system disease, pulmonary edema, and death.
  • Coxsackievirus A16 and enterovirus 71 are the most common agents of HFMD. In addition, coxsackievirus A6 seems to be emerging.
  • Neurologic and cardiopulmonary involvement are more often associated with enterovirus 71 infection.
  • In March 2012, 63 cases of severe HFMD were reported in Alabama, California, Connecticut, and Nevada. Fifteen of the patients were adults, and more than half had positive sick contacts. Of the 34 patients who underwent serologic testing, 25 were positive for coxsackievirus A6, an unusual pathogen for HFMD in the United States, associated with more severe skin findings.
  • Treatment focuses on supportive care and prevention.



Hand, foot, and mouth disease (HFMD) is typically a benign childhood infection—except when it isn’t so benign or when it occurs in adults.

The usual presentation is in a child with fever, oral ulcerations, and papules on the palms of the hands and the soles of the feet.1 However, severe complications can occur, including central nervous system involvement and cardiopulmonary failure, and can lead to significant morbidity and even death.2 Fortunately, these complications are rare.

Less common in North America than in other regions, HFMD has recurrently broken out in many areas of Southern Asia and the surrounding Pacific region. However, several North American outbreaks have been documented in recent years and have affected unexpected numbers of immunocompetent adults, demonstrating that this disease is of worldwide importance in adults as well as children.3

Because HFMD has the potential to reach epidemic levels in the United States, early recognition is paramount, and primary care physicians need to be familiar with its common signs and symptoms.


HFMD occurs all around the world, exhibiting seasonal variation in temperate climates. In these locations, individual cases and regional outbreaks usually occur in the spring, summer, and fall. No sexual predisposition has been documented. Most symptomatic cases are in children under the age of 10.


The disease was first described more than 40 years ago, with several large outbreaks in the last 16 years.

1998—An outbreak in Taiwan affected more than 1.5 million people, mostly children. Severe cases numbered just over 400, and 78 children died.4

2008—China,5 Singapore,6 Vietnam,7 Mongolia,8 and Brunei9 were stricken with an outbreak that affected 30,000 people and led to more than 50 deaths.

2009—An outbreak in the Henan and Shandong provinces of eastern China killed 35 people.10

2010—In several southern Chinese regions, more than 70,000 people were infected, with almost 600 deaths.11

2011 to the present. The United States has had several outbreaks in the last 3 years. Although HFMD is not one of the diseases that must be reported to public health authorities in the United States, from November 2011 to February 2012 the US Centers for Disease Control and Prevention (CDC) received reports of 63 possible cases: 38 in Alabama, 17 in Nevada, 7 in California, and 1 in Connecticut.1 Fifteen of the patients were adults, and more than half had contacts who were sick.

The most recent US outbreak, in Alabama,12 was atypical because it occurred in the winter.


HFMD is caused by infection with a variety of viruses in the genus Enterovirus, a large group that in turn is part of the larger Picornaviridae family.13 The taxonomy of this genus is complicated and subject to revision; species include coxsackieviruses, polioviruses, enteroviruses, and echoviruses. They are all small, nonenveloped, single-stranded RNA viruses.

The most common strains that cause HFMD are coxsackievirus A16 and enterovirus 71. In addition, coxsackievirus A6 may be emerging, and many other coxsackievirus strains have been directly implicated, including A5, A7, A9, A10, B2, and B5.

Coxsackievirus A16 is the leading cause of HFMD.

Enterovirus 71 is the second most common cause of HFMD and has also caused outbreaks. It usually results in benign disease. However, among the causes of HFMD, it is associated with more prominent central nervous system involvement14 and is the most common cause of viral meningoencephalitis in children.

Coxsackievirus A6. In December 2011, the California Department of Public Health isolated a strain of coxsackievirus A6 that caused extensive rash and nail shedding.15 Among the 63 possible cases of HFMD reported to the CDC from November 2011 to February 2012, specimens for clinical testing were obtained in 34, and 25 of those demonstrated coxsackievirus A6 infection.3

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