Epidemiology^[1]

• It occurs worldwide, with a peak incidence in the summer and autumn in temperate climates.
• It is most common among infants and children aged younger than 10 years.^[1]
• Adults generally develop less severe symptoms than children although severe cases in immunocompromised adults have been reported.^[2]
• It is very infectious so epidemics can occur.
• Epidemics have occurred in Singapore and Taiwan in recent years. These were caused by enterovirus 71.^[3]
• It is not a notifiable illness.

Transmission and incubation period^[1]

• Transmission is commonly by the faecal-oral route. Contact with skin lesions and oral secretions (including coughs and sneezes) can also allow transmission.
• The incubation period is one week.^[1]
• An infected individual can continue to shed the virus in the stools for some weeks.^[1]

Presentation^[1][4]

• Prodrome: includes fever, malaise and loss of appetite. There may be a sore mouth or throat. Enterovirus 71 can cause vomiting.

• Mouth lesions: after the prodrome, lesions develop in the mouth. These may be on the buccal mucosa, tongue and hard palate. The uvula, gums and lips are sometimes involved. They begin as macular lesions that progress to vesicles which then erode. Mouth lesions are typically yellow ulcers surrounded by red haloes. They may be uncomfortable. Children aged under 5 years tend to have worse symptoms than older children.

• Skin lesions: 75% also develop skin lesions.^[1] They are mainly on the palms, soles and between the fingers and toes. They may itch. They start as erythematous macules but rapidly progress to grey vesicles with an erythematous base. Lesions may also appear on the trunk, thighs, buttocks and/or genitalia. These lesions are mainly an erythematous maculopapular rash rather than the papulovesicular ones found on the hands and feet. The rash lasts about 3 to 6 days.

Differential diagnosis^[1][4]

• Herpangina (caused by similar Coxsackieviruses or echoviruses with lesions similar to hand, foot and mouth disease, but limited to the posterior oral cavity with no skin lesions).
• Herpes simplex and herpes zoster viruses.
• Chickenpox.
• Kawasaki disease.
• Erythema multiforme (Stevens-Johnson syndrome).
• Viral pharyngitis.
• Toxic epidermal necrolysis.

Investigations^[1][4]

• Diagnosis is usually clinical.
• The virus can be cultured and detected from the lesions or stool specimens.
• It may also be detected serologically.

Management^[1][4]

This is generally supportive:

• Parents need to be reassured that it is unrelated to foot and mouth disease in animals.
• If the mouth is uncomfortable, dehydration may result from poor fluid intake. Encourage adequate fluid intake. Admission to hospital is rarely required.
• Antipyretic analgesics, such as paracetamol or ibuprofen, are usually all that is required.
• If the mouth is very painful, an analgesic such as benzydamine or lidocaine oral gel may be helpful.
• Antibiotics are only required if secondary infection of skin lesions occurs.
• Intravenous immunoglobulin and milrinone have been found to be helpful in a few cases.
• Any cardiovascular or neurological complications need to be treated appropriately (see below).

Indications to consider hospital referral

• Signs of significant dehydration (particularly in a child).
• Neurological signs or symptoms, eg myoclonic jerks, persistent or severe headaches.
• Persistent oral ulcers.

Complications^[1][4]

Complications are rare. They include the following:

• Secondary infection of skin that has been scratched.
• Painful stomatitis due to oral involvement. This can lead to dehydration.
• Neurological involvement and meningitis are more likely if enterovirus 71 is the causative organism.^[5] Neurological involvement can include encephalitis, encephalomyelitis, polio-like syndrome, cerebellar ataxia, transverse myelitis and Guillain-Barré syndrome.
• Cardiopulmonary complications include myocarditis, interstitial pneumonitis and pulmonary oedema.
• If infection occurs during pregnancy, there are reports of spontaneous abortion.^[1] If infection occurs in the third trimester, there is a chance of neonatal infection.

Prognosis^[1][4]

• This is generally excellent with a full recovery in most people.
• Symptoms tend to improve within 3-6 days, usually with full resolution of skin and mouth lesions within 7-10 days.^[1]

Prevention^[1][4][6]

• Attention to hand washing in the family should reduce further spread. The virus may be excreted in the faeces for some weeks.
• Opinions about exclusion from school vary, since the virus can be excreted for weeks after clinical signs of infection have resolved.^[7] Most authorities advise keeping the child off school/nursery while they are unwell. They can, however, return before all of the lesions have healed.^[8]