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A 1-year-old boy presents to the clinic with lesions on his face, trunk and extremities (Figure 134-1). Two days ago, the patient had a fever of 103°F and was very irritable. No one in the family has this rash. On exam, a flat oval vesicle was seen on the hand following skin lines (Figure 134-2). The physician diagnosed hand, foot, and mouth disease. She suspected that it was caused by Coxsackievirus A6 because of the high fever and the wide distribution of lesions. The physician recommended fluid and antipyretics as needed, and the disease resolved without complications.

FIGURE 134-1

A 1-year-old boy with hand-foot-mouth disease likely to be caused by Coxsackievirus A6. PCR confirmed presence of enterovirus. (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE 134-2

A single flat, gray, oval vesicular lesion on ventral finger of the child in Figure 134-1. (Reproduced with permission from Richard P. Usatine, MD.)


Hand, foot, and mouth disease (HFMD) is a viral illness that may affect humans and some animals and has a distinct clinical presentation. The disease occurs worldwide and was typically caused by Coxsackievirus A16. Worldwide outbreaks with a more virulent Coxsackievirus A6 started as early as 2008.1


  • In temperate climates, the peak incidence is in summer and early fall. Outbreaks and sporadic episodes have occurred during winter months.2

  • Typical HFMD caused by Coxsackievirus A16 generally has a mild course. It mostly occurs in infants and children up to 8 years old.3

  • Atypical HFMD caused by Coxsackievirus A6 (CVA6) has a more severe course and affects young children and adults.1,2

  • There is no racial or gender predilection.


  • HFMD is most commonly caused by members of the enterovirus genus, especially Coxsackievirus. Epidemic infections in the United States were usually caused by Coxsackievirus A16 and enterovirus 71 before Coxsackievirus A6 began to appear.

  • Outbreaks of strains of EV71 enterovirus producing large epidemics of HFMD with significant morbidity and mortality have occurred in east and southeast Asia. Enterovirus 71 was first isolated in California, USA, in 1969.4

  • Atypical presentations of HFMD caused by Coxsackievirus A6 have been reported in Asian and Europe since 2008 and in the United States since 2011.5-8 In the fall of 2011 and early winter of 2012, 63 cases of apparent but more severe HFMD from four U.S. states were reported to the Centers for Disease Control and Prevention (CDC). Polymerase chain reaction (PCR) and gene sequencing detected an A6 strain of coxsackievirus in 74% of clinical specimens from 34 cases.5

  • Coxsackievirus infections are highly contagious. ...

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