What virus causes hand‑foot‑mouth disease in children, presenting with vesicular lesions that start on the hands and spread to the forearms and feet?

Hand, Foot, and Mouth Disease (HFMD) is Not a Pox Virus

HFMD is caused by enteroviruses (primarily Coxsackievirus A16, Coxsackievirus A6, and Enterovirus 71), not pox viruses, and presents with characteristic vesicular lesions on hands, feet, and mouth. 1, 2

Causative Agents

• Enteroviruses from the Picornaviridae family cause HFMD, with the most common pathogens being Coxsackievirus A16, Enterovirus 71 (EV-A71), Coxsackievirus A6, and Coxsackievirus A10. 3, 4

• EV-A71 is associated with more severe outbreaks, particularly in Asia, and can cause neurological complications including encephalitis, meningitis, and acute flaccid paralysis. 5, 2

• Recent epidemiological shifts show Coxsackievirus A6 causing more extensive cutaneous disease with atypical presentations including widespread vesicular eruptions beyond the classic distribution. 6

Clinical Presentation Pattern

• Fever typically appears first (1-2 days before the rash), followed by oral lesions that develop as small red spots progressing to painful vesicles and ulcers on the tongue, gums, and inside of the cheeks. 1

• The characteristic vesicular rash appears 1-2 days after fever onset, affecting the hands (including palms), feet (including soles), and may extend to the forearms, legs, buttocks, and genital area. 1, 3

• Unlike pox viruses (such as varicella), HFMD lesions are concentrated on the hands, feet, and mouth rather than being widely distributed across the trunk. 1

Diagnostic Approach

• Vesicle fluid samples have the highest viral loads and are ideal for RT-PCR testing targeting the 5′ non-coding region, which is the preferred diagnostic method due to sensitivity and specificity. 2

• Respiratory samples and stool specimens can also be used for diagnosis, particularly important for EV-D68 which is rarely detectable in CSF or stool. 5

• Clinical diagnosis is typically sufficient based on the characteristic distribution pattern: oral ulcers plus vesicular lesions on hands and feet in a child under 10 years of age. 3

Critical Differential Diagnoses

• Distinguish from herpes simplex virus infection, which has available antiviral treatment (acyclovir) whereas HFMD requires only supportive care. 2

• Rule out varicella (chickenpox), which presents with widely distributed lesions starting on the trunk rather than the acral distribution of HFMD. 1

• Consider Kawasaki disease if there is persistent high fever with diffuse erythema, conjunctival injection, strawberry tongue, and cervical lymphadenopathy rather than vesicular lesions. 1

Management

• Treatment is entirely supportive with oral analgesics (acetaminophen or NSAIDs) for pain and fever control. 2, 3

• For oral lesions causing significant discomfort: apply white soft paraffin to lips every 2 hours, use benzydamine hydrochloride oral rinse before eating, and consider betamethasone sodium phosphate mouthwash for severe involvement. 2

• For infants with severe oral pain: nonnutritive sucking with a pacifier reduces distress, and 25% sucrose solution (2 mL, 1 mL per cheek) provides analgesia during feeding attempts in infants under 6 months. 2

• Intensive skin care with urea-containing moisturizing creams for hand and foot lesions, avoiding friction and heat exposure to affected areas. 2

Warning Signs Requiring Urgent Evaluation

• Persistent high fever, lethargy, severe headache, stiff neck, or unusual irritability suggest potential neurological complications (meningitis, encephalitis, acute flaccid paralysis), particularly with EV-71 infections. 1

• Respiratory distress may indicate rare but serious complications like neurogenic pulmonary edema. 1

• Monitor for signs of secondary bacterial infection: increased redness, warmth, purulent drainage, or worsening pain. 2

Transmission and Return to School

• Children can return to daycare/school once fever has resolved without medications and mouth sores have healed, even if skin rash persists. 2

• Hand hygiene with soap and water (more effective than alcohol-based sanitizers) is the most important preventive measure. 2, 7

• Viral shedding continues in stool for several weeks after symptoms resolve, but exclusion based solely on healing skin lesions is unnecessary. 7