Etiology
The most common viruses implicated are a group of enteroviruses known as the coxsackieviruses. Coxsackievirus A16 (CV-A16) infection is the most common cause, but A4 through A7, A9, and A10 infections also occur.[1][2][3][4][5] Enterovirus 71 (EV71) also causes this disease, but a more severe version.[1][2][3][4][5][7][8][9] EV71 infection is uncommon in the US and Europe. Etiological changes in the main pathogenic agents of hand-foot-and-mouth disease have been noted in Hunan province in China. The number of patients hospitalized with the disease caused by EV71 and CV-A16 declined between 2014 and 2017, while the number of cases caused by other enteric viruses increased.[14] The enteroviruses are icosahedral nonenveloped viruses that are approximately 30 nanometers in diameter. The genome is made of a single-stranded linear molecule of RNA. Enteroviruses resist lipid solvents and tolerate a wide range of pH and temperature. They are inactivated at temperatures of >122°F (>50°C), but remain infectious at refrigerator temperatures.
Pathophysiology
The infection occurs when a susceptible person is exposed to the virus by means of direct contact with nose and throat discharges, saliva, vesicle fluid, or fecal material from an infected person. The virus may persist in fecal material for up to 1 month. After contact, the virus spreads to regional lymph nodes within 24 hours and viremia rapidly follows, with spread of the virus to the oral mucosa and skin causing the vesicular rash. The incubation period is 4 to 7 days; however, there may be a prodromal period of 3 to 4 days. Lesions in the mouth heal within 1 week, and lesions on the hands and feet may last up to 10 days.[1][2][3][4][5][6][7]
Classification
Viral classification
Hand-foot-and-mouth disease is due to infection by some of the enteroviruses. The most common viruses implicated are the coxsackieviruses. Coxsackievirus A16 infection is the most common cause, but A4 through A7, A9, and A10 infections also occur.[1][2][3][4][5][6]
Enterovirus 71 (EV71) also causes this disease, but a more severe version.[1][2][3][4][5][6][7][8][9][10] However, although outbreaks due to EV71 infection have been reported in the US, they are uncommon.
Enteroviruses belong to the Picornaviridae family of viruses; polioviruses, coxsackieviruses (groups A and B), and echoviruses are groups of enteroviruses. More recently identified enteroviruses have not been included in the original classification and have been allocated numbers (i.e., serotypes 68 to 71).
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