What is the initial approach to managing a patient with suspected Hand, Foot, and Mouth (HFM) disease?

Differential Diagnosis of Hand, Foot, and Mouth Disease

The differential diagnosis for Hand, Foot, and Mouth Disease (HFMD) includes erythema multiforme, herpes simplex virus infection, herpangina, varicella, measles, aphthous stomatitis, and in children with atopic dermatitis, eczema herpeticum. 1

Key Distinguishing Features to Assess

Primary Differentials to Consider

Herpes Simplex Virus (HSV) Infection

• Critical distinction: HSV has available antiviral treatment options (acyclovir), whereas HFMD does not, making this differentiation clinically essential 2
• HSV typically presents with grouped vesicles on an erythematous base, often localized to perioral areas or a single dermatome 1
• Tzanck smear or PCR can definitively distinguish HSV from HFMD 2
• In children with atopic dermatitis, "eczema coxsackium" may closely mimic eczema herpeticum, requiring careful evaluation 3

Erythema Multiforme

• Presents with target lesions (iris-like appearance with central clearing) rather than the papulovesicular rash of HFMD 1
• Distribution typically involves extensor surfaces and may include palms/soles but lacks the oral ulcerations characteristic of HFMD 1
• Often triggered by HSV or medications 1

Varicella (Chickenpox)

• Lesions appear in crops with different stages of evolution (macules, papules, vesicles, crusts) simultaneously 1
• Distribution is centripetal (trunk predominant) rather than acral 1
• Oral lesions are less prominent than in HFMD 1

Herpangina

• Caused by similar enteroviruses but lesions are confined to the posterior oropharynx (soft palate, uvula, tonsillar pillars) 4
• Lacks the characteristic hand and foot involvement of HFMD 4

Measles

• Presents with Koplik spots (white spots on buccal mucosa) rather than painful oral ulcerations 1
• Maculopapular rash begins on face and spreads cephalocaudally, not acral distribution 1
• Associated with high fever, cough, coryza, and conjunctivitis 1

Clinical Approach to Differentiation

History Elements to Elicit

• Age of patient (HFMD most common in children <5 years, though adults can be affected) 1, 4
• Fever pattern (low-grade fever typical in HFMD) 1
• Presence of atopic dermatitis (increases risk of atypical presentations mimicking HSV) 3
• Exposure history and season (HFMD outbreaks occur spring to fall in North America) 1
• Vaccination status (measles, varicella) 1

Physical Examination Specifics

• Oral cavity: HFMD presents with painful ulcerations on tongue, buccal mucosa, and hard palate; herpangina affects only posterior pharynx 1, 4
• Skin lesions: HFMD shows maculopapular or papulovesicular rash specifically on palms and soles, though widespread exanthema involving legs may occur 2, 1
• Lesion morphology: HFMD lesions are typically oval, gray vesicles with erythematous halos, not grouped like HSV 3
• Distribution pattern: Acral (hands, feet, mouth) is classic for HFMD versus other patterns for differentials 1

Diagnostic Testing When Needed

When Clinical Diagnosis is Equivocal

• RT-PCR of vesicle fluid (highest viral load), respiratory samples, or stool specimens can confirm HFMD 2
• RT-PCR targeting the 5' non-coding region is the preferred diagnostic method for its sensitivity and specificity 2
• Consider testing to distinguish from HSV when antiviral treatment would change management 2

Atypical Presentations Requiring Heightened Awareness

Eczema Coxsackium

• Occurs in children with atopic dermatitis where eczematous skin becomes superinfected with coxsackievirus 3
• May closely resemble eczema herpeticum, making HSV testing critical 3
• Lesions concentrate in areas of pre-existing eczema 3

Post-HFMD Nail Changes

• Nail shedding (onychomadesis) may occur weeks after acute HFMD, presenting as isolated finding 3
• Consider antecedent HFMD in differential when evaluating unexplained nail changes in children 3

Common Pitfalls to Avoid

• Failing to distinguish HFMD from HSV: This is the most critical error as HSV requires antiviral therapy while HFMD does not 2
• Missing severe EV-A71 cases: Enterovirus 71 causes more severe disease with potential neurological complications (encephalitis, acute flaccid paralysis) and requires closer monitoring 2, 4
• Overlooking atypical distributions: Widespread exanthema beyond classic hand-foot-mouth distribution can occur, particularly involving the legs 2
• Dismissing the diagnosis in older children or adults: While most common under age 5, HFMD can affect any age group 1, 4