What are the diagnostic criteria for Hand, Foot, and Mouth Disease (HFMD)?

Diagnostic Criteria for Hand, Foot, and Mouth Disease (HFMD)

The diagnosis of Hand, Foot, and Mouth Disease is primarily clinical, based on the presence of characteristic vesicular lesions on the hands, feet, and in the oral cavity, typically accompanied by fever.

Clinical Presentation

Cardinal Features

• Fever (typically low-grade but can exceed 102.2°F/39°C), usually the first symptom 1, 2
• Oral lesions: small red spots that progress to painful vesicles and ulcers, particularly on the tongue, gums, and inside of the cheeks 1, 2
• Vesicular rash on hands and feet: typically maculopapular or vesicular lesions 3, 4

Disease Progression

• Initial symptoms include fever, general discomfort, malaise, and irritability 2
• Oral lesions typically develop first (1-2 days after fever onset) 2
• Skin lesions appear as vesicles on hands and feet, sometimes extending to buttocks 4
• Fever usually subsides within 3-4 days, but oral ulcers may persist for 7-10 days 2

Diagnostic Approach

Clinical Diagnosis

• Diagnosis is primarily based on clinical presentation and physical examination findings 1, 3
• The combination of fever with characteristic vesicular lesions on hands, feet, and in the oral cavity is highly suggestive of HFMD 2, 4
• Widespread exanthema beyond the classic distribution (hands, feet, mouth) may occur, involving the legs, buttocks, arms, and trunk in up to 87.6% of cases 4

Laboratory Confirmation

• Reverse transcriptase PCR (RT-PCR) is the preferred diagnostic method due to its sensitivity and specificity 1
• Optimal specimens for testing include:
  • Vesicle fluid samples (highest viral loads) 1
  • Respiratory samples 1
  • Stool specimens 1

Differential Diagnosis

• Chickenpox: HFMD lesions are typically concentrated on hands, feet, and mouth rather than being widely distributed 2
• Kawasaki disease: HFMD presents with vesicular lesions rather than diffuse erythema and does not typically have the persistent high fever characteristic of Kawasaki disease 2
• Herpangina: primarily affects the posterior oral cavity without the characteristic hand and foot lesions 3

Warning Signs of Complications

• Persistent high fever 2
• Lethargy or unusual irritability 2
• Severe headache or stiff neck (suggesting meningeal involvement) 2, 5
• Respiratory distress (may indicate rare but serious complications like neurogenic pulmonary edema) 2, 6
• Neurological symptoms such as myoclonic jerks, seizures, or acute flaccid paralysis 5

Special Considerations

• Immunocompromised patients may experience more severe disease and should be monitored closely 1
• Atypical presentations may occur, particularly with Coxsackievirus A6 infections, which can cause more widespread rash including peri-oral involvement 4
• Fatal cases may present with minimal skin manifestations but rapid deterioration 6

Etiologic Agents

• Common causative agents include:
  • Coxsackievirus A16 (CV-A16) 3, 7
  • Enterovirus 71 (EV-A71) - associated with more severe outbreaks and neurological complications 7, 5
  • Coxsackievirus A6 (CV-A6) - increasingly associated with atypical and widespread rash 4, 7
  • Coxsackievirus A10 (CV-A10) 7

Hand, foot, and mouth disease is primarily a clinical diagnosis that relies on the identification of characteristic vesicular lesions in the typical distribution pattern, accompanied by fever and other constitutional symptoms. Laboratory confirmation through RT-PCR can be helpful in uncertain cases or during outbreaks.