Acyclovir is NOT Effective for Hand, Foot, and Mouth Disease in Pediatric Patients
Acyclovir should not be used to treat hand, foot, and mouth disease (HFMD) in children, as it has no activity against the causative enteroviruses and there is no evidence supporting its use for this condition.
Why Acyclovir Does Not Work for HFMD
Wrong Viral Target
- Acyclovir is a synthetic nucleoside analog that specifically inhibits replication of human herpes viruses, including varicella-zoster virus (VZV) and herpes simplex virus (HSV), but has no activity against enteroviruses 1
- HFMD is caused by enteroviruses—primarily coxsackieviruses A6, A10, A16, and enterovirus 71—not herpes viruses 2, 3, 4
- The mechanism of action of acyclovir targets herpes virus DNA polymerase, which is completely different from the RNA replication machinery of enteroviruses 1
Current Standard of Care for HFMD
- Treatment of HFMD is supportive care only; no antiviral therapy is generally recommended 2, 3
- The mainstay of treatment remains symptomatic management, as most cases follow a benign, self-limiting course resolving within 7-10 days 2, 3, 4
- For severe HFMD cases with neurological or cardiopulmonary complications (primarily from enterovirus 71), treatment may include mechanical ventilation and potentially ribavirin—not acyclovir 2
Critical Diagnostic Pitfall to Avoid
Distinguishing HFMD from Herpes Infections
- In children with atopic dermatitis, HFMD can mimic herpetic superinfection, a condition called "eczema coxsackium" 3
- This atypical presentation may resemble eczema herpeticum (which DOES respond to acyclovir), but the causative agent is coxsackievirus, not HSV 3
- For true eczema herpeticum caused by HSV, the CDC recommends oral acyclovir 20 mg/kg per dose (maximum 400 mg/dose) three times daily for 5-10 days 5, 6
- The key distinction: if viral culture or PCR confirms enterovirus/coxsackievirus rather than HSV, acyclovir will be ineffective and should be discontinued 3
What Actually Works
Supportive Care Measures
- Adequate hydration and pain control for oral lesions 3, 4
- Hygiene measures to prevent transmission 3
- Monitoring for severe complications (encephalitis, meningitis, pulmonary edema) particularly in children under 3 years 4, 7
Future Directions
- An inactivated enterovirus A71 vaccine has been approved in China and provides high-level protection against EV-A71-related HFMD, but does not protect against other causative enteroviruses 4
- Currently, no effective antiviral therapies are available for enterovirus infections, though novel agents are in development 2, 4, 7