What is Hand, Foot, and Mouth Disease (HFMD)?
Hand, Foot, and Mouth Disease is a highly contagious viral illness caused primarily by enteroviruses—most commonly coxsackievirus A16 (CV-A16), enterovirus 71 (EV-A71), and increasingly coxsackievirus A6 (CV-A6)—that predominantly affects children under 5 years of age but can also occur in adults, characterized by fever, oral lesions, and a vesicular rash on the hands and feet. 1
Causative Agents
The viral etiology determines disease severity and clinical presentation:
- Coxsackievirus A16 (CV-A16) is the most common cause of classic, mild HFMD 1
- Enterovirus 71 (EV-A71) carries the highest risk for severe complications, including brain stem encephalitis, meningoencephalitis, acute flaccid paralysis, and pulmonary edema, and has been responsible for large outbreaks with rare but severe cases of rhomboencephalitis, particularly in Asia and more recently in Europe 1, 2
- Coxsackievirus A6 (CV-A6) has emerged as an increasingly important pathogen causing more severe outbreaks worldwide with atypical features, including widespread exanthema beyond classic distribution, more severe skin manifestations, and association with onychomadesis (nail shedding) occurring 1-2 months after fever onset 1, 3
Clinical Presentation
Initial Symptoms
- Fever is a common constitutional symptom, usually low-grade but can exceed 102.2°F/39°C 2, 4
- Malaise and general discomfort typically accompany the fever 4
- Sore throat often develops early in the illness 5
Characteristic Lesions
- Oral lesions: Painful vesicles and ulcers develop in the mouth, affecting the oral mucosa 2, 6
- Hand and foot lesions: Tender vesicular or maculopapular eruptions appear on the palms and soles 6, 5
- Atypical presentations: CV-A6 causes widespread exanthema beyond the classic distribution, involving the legs and other body areas 2, 1
Late Manifestations
- Beau's lines (deep transverse nail grooves) may appear approximately 1-2 months after fever onset, representing a delayed sequela rather than active disease 2
- Periungual desquamation typically begins 2-3 weeks after onset of fever 2
- Onychomadesis (nail shedding) is particularly associated with CV-A6 infections 1, 7
Epidemiology and Transmission
- HFMD predominantly affects children under 5 years of age, though adults can also be affected, particularly with CV-A6 strains 1, 3
- The disease is highly contagious, with adults most infectious during the first week of illness and viral shedding continuing for up to five days after symptom onset 4
- In temperate-climate countries, outbreaks occur mostly but not exclusively during summer and autumn months 7
Complications
While most cases follow a benign, self-limiting course, serious complications can occur:
- Neurological complications: Encephalitis/meningitis, acute flaccid myelitis (AFM), and acute flaccid paralysis (AFP) can occur in severe cases, particularly with EV-71 2, 4
- Cardiopulmonary complications: Pulmonary edema and cardiopulmonary failure are rare but potentially fatal 1, 8
- Case severity and fatality: In China, the case severity rate has been estimated at 1%, with a case fatality rate at 0.03%, with EV-A71 involved in more than 90% of fatal cases 7
Diagnosis
- Clinical diagnosis is primarily based on the characteristic distribution of lesions 4
- Laboratory confirmation: Reverse transcriptase PCR (RT-PCR) targeting the 5′ non-coding region is the preferred diagnostic method due to its sensitivity and specificity 2
- Optimal specimens: Vesicle fluid samples have the highest viral loads and are ideal for testing 2, 1, 4
- Alternative specimens: Respiratory samples and stool specimens can also be used for diagnosis 2, 1
- For neurological presentations: Respiratory specimens should always be collected 1
Critical Differential Diagnoses
- Distinguish from herpes simplex virus infection, as HSV has available antiviral treatment whereas HFMD does not 2
- Rule out drug hypersensitivity reactions, which can also present with palmar-plantar rash 2, 4
- Differentiate from Kawasaki disease (HFMD has vesicular lesions vs. diffuse erythema) 2
- Consider syphilis, meningococcemia, and Rocky Mountain spotted fever in atypical presentations with palmar-plantar involvement 2, 4
Management
Supportive Care
- Oral analgesics: Acetaminophen or NSAIDs for a limited duration to relieve pain and reduce fever 2, 4
- Oral lesion management: Mild toothpaste and gentle oral hygiene 2, 4
- Skin care: Intensive moisturizing of hands and feet with urea-containing creams, avoiding friction and heat exposure to affected areas 2
- Zinc oxide: May help reduce itchiness in skin lesions by forming a protective barrier 2, 4
Specific Symptom Management
For severe oral involvement, consider benzydamine hydrochloride oral rinse or spray every 3 hours, particularly before eating, and betamethasone sodium phosphate mouthwash four times daily 2
Monitoring
- Immunocompromised patients may experience more severe disease and should be monitored closely 2, 4
- Monitor for signs of secondary bacterial infection, including increased redness, warmth, purulent drainage, or worsening pain 2
- If evidence of infection has not resolved after 4 weeks, re-evaluate and consider alternative diagnoses 2
Prevention and Control
- Hand hygiene is the most important preventive measure, with thorough handwashing with soap and water being more effective than alcohol-based hand sanitizers 2
- Environmental cleaning, particularly of toys and objects that may be placed in children's mouths, is crucial 2
- Avoid sharing utensils, cups, or food 2
- Children with HFMD should avoid close contact with others until fever resolves and mouth sores heal 2
Return to Activities
- Children can return to daycare once fever has resolved and mouth sores have healed, even if skin rash is still present, as exclusion based solely on healing skin lesions is not necessary 2
- Adults can generally return to work or normal activities once fever has resolved, mouth sores have healed, and no new lesions have appeared for 48 hours 4