How is hand, foot, and mouth disease diagnosed and treated?

Diagnosing Hand, Foot, and Mouth Disease

Clinical Diagnosis

Hand, foot, and mouth disease is diagnosed clinically based on the characteristic presentation of fever followed by vesicular lesions in a typical distribution on the hands, feet, and mouth. 1

Initial Presentation

• Fever is typically the first symptom, often low-grade but can exceed 102.2°F (39°C), accompanied by malaise, sore throat, and irritability in young children 2
• Constitutional symptoms including cough, rhinitis, and occasionally gastrointestinal symptoms (nausea, vomiting, diarrhea) may precede the rash 2
• The oral lesions usually appear first, making dentists and primary care providers often the first to encounter the disease 3

Characteristic Lesion Pattern

• The exanthem begins as small pink macules that evolve into vesicular lesions with highly characteristic distribution on palms, soles, and oral mucosa 2
• Oral vesicles and ulcerations typically develop on the tongue, buccal mucosa, and palate 4
• Widespread exanthema beyond the classic distribution may occur, particularly involving the legs and buttocks 1
• The vesicles are typically discrete, unlike the diffuse erythema seen in Kawasaki disease 1, 2

Laboratory Confirmation

When laboratory confirmation is needed, reverse transcriptase PCR (RT-PCR) targeting the 5′ non-coding region is the preferred diagnostic method due to its sensitivity and specificity. 1

Specimen Collection Priority

• Vesicle fluid samples have the highest viral loads and are ideal for testing 1
• Respiratory samples (throat swabs) or stool specimens can also be used for RT-PCR diagnosis 1
• Testing is typically reserved for severe cases, outbreak investigations, or when the diagnosis is uncertain 4

Critical Differential Diagnoses

It is crucial to distinguish HFMD from conditions requiring specific treatment or indicating serious systemic disease. 1

Must-Rule-Out Conditions

• Herpes simplex virus infection: This distinction is critical because HSV has available antiviral treatment options whereas HFMD does not 1
• Kawasaki disease: HFMD presents with vesicular lesions versus the diffuse erythema of Kawasaki disease; Kawasaki also features persistent high fever (≥5 days) and other criteria including conjunctival injection and cervical lymphadenopathy 5, 1, 2
• Drug hypersensitivity reactions: Can present with palmar-plantar rash but typically have medication exposure history 1

Other Considerations in Atypical Presentations

• Syphilis, meningococcemia, and Rocky Mountain spotted fever should be considered when palmar-plantar involvement occurs with atypical features 1, 2
• Chickenpox differs by having widely distributed vesicles rather than the concentrated hand-foot-mouth distribution 2
• Herpangina, recurrent aphthae, and erythema multiforme should be considered in the differential 3

Identifying Severe Disease

Enterovirus A71 (EV-A71) is associated with more severe outbreaks and neurological complications, particularly in Asia. 1

Warning Signs Requiring Urgent Evaluation

• Neurological complications including encephalitis/meningitis, acute flaccid myelitis, or acute flaccid paralysis 1
• Circulatory failure secondary to myocardial impairment 4
• Neurogenic pulmonary edema secondary to brainstem damage 4
• Children under 3 years of age are at highest risk for severe complications 6

Common Diagnostic Pitfalls

• Lesions may be faint and difficult to visualize, requiring careful examination of all typical sites including between toes and on the palms 7
• Not all classic features are present simultaneously; watchful waiting may be necessary before diagnosis can be confirmed 5
• By the time HFMD is diagnosed, the child has likely been infectious for days to weeks, making isolation after diagnosis of limited additional benefit 1
• Adults can contract HFMD from infected children, though it is less commonly recognized in this population 7