Laboratory Studies

Generally, no laboratory studies are necessary for hand-foot-and-mouth disease (HFMD). Leukocyte counts are 4000-16,000/µL. Occasionally, atypical lymphocytes are present.

Recent studies show that elevated serum concentration of C-reactive protein (CRP) and fasting and elevated blood glucose were significantly higher in severe cases than in mild ones.^[9]

The virus can be isolated from swabs of the vesicles or mucosal surfaces or from stool specimens and then inoculated into mice or cultured on viral tissue media.

Neutralizing antibodies rapidly disappear; thus, they are usually detectable only in the acute phase.

High levels of complement-fixing antibodies are present in the convalescent phase.

Studies have illustrated the usefulness of a molecular assay using polymerase chain reaction primers to arrive at a rapid and specific diagnosis in order to distinguish between coxsackievirus A16 and enterovirus 71.^[22]This may hold promise in future outbreaks because infections with enterovirus 71 tend to be associated with more severe complications and fatalities. One study suggests that swabs be collected within 4 days of HFMD onset to increase diagnostic yield.^[23]

A 2020 study showed promising results for effective early noninvasive diagnosis of enterovirus A71 infection in children using saliva swabs, with detection of IgA-specific antibodies to enterovirus A71.^[24]

Imaging Studies

Acute flaccid paralysis associated with enterovirus 71–infected hand-foot-and-mouth disease (HFMD) can be seen in severe cases. MRI is an effective modality to investigate neurological complications associated with the enterovirus 71 epidemics. Involvement of posterior portions of the medulla oblongata and pons, and bilateral anterior horns of the spinal cord, are characteristic findings.^[25]

Histologic Findings

Classic histopathologic findings of hand-foot-and-mouth disease (HFMD) include an intra-epidermal vesicle that contains neutrophils and eosinophilic cellular debris. The adjacent epidermis has reticular degeneration, that is, intercellular and intracellular edema. The dermis has a mixed infiltrate. Eosinophilic intranuclear inclusions are observed with electron microscopic studies.

Neuropathology in fatal cases of enterovirus 71 infection have shown features of an acute encephalitis involving the brain stem and spinal cord.^[26]

Treatment & Management

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Media Gallery

The lower lip has an ulcer with an erythematous halo.
The tongue has an ulcer with an erythematous halo.
A typical cutaneous lesion has an elliptical vesicle surrounded by an erythematous halo. The long axis of the lesion is oriented along the skin lines.