Can hand‑foot‑and‑mouth disease initially present with a rash behind the knees, and what is the appropriate management for this presentation?

Hand-Foot-and-Mouth Disease Does Not Typically Present Behind the Knees Initially

A rash presenting behind the knees as the initial manifestation is not consistent with hand-foot-and-mouth disease (HFMD), and this presentation should prompt consideration of alternative diagnoses.

Classic vs. Atypical HFMD Presentations

Classic HFMD Distribution

The typical presentation of HFMD involves:

• Oral lesions (painful ulcers on tongue, gums, inside cheeks)
• Vesiculopapular rash on hands and feet, including palms and soles 1, 2
• Buttocks involvement is common
• Lesions appear 2-4 days after fever onset 3

Atypical HFMD Patterns (Primarily CVA6-Associated)

While atypical presentations have been increasingly recognized since 2008, particularly with Coxsackievirus A6 (CVA6) infections, these involve 4, 5, 6:

• Widespread distribution to arms, legs, trunk, and face (87.6% had sites beyond classic locations) 7
• Perioral rash (strongly associated with CVA6) 7
• Bullous or vesiculobullous lesions (36% of atypical cases) 6
• Eczema coxsackium in children with atopic dermatitis 8, 9
• Gianotti-Crosti-like eruptions 5

However, even in these atypical presentations, the popliteal fossa (behind the knees) is not described as a primary or initial site of involvement 4, 7, 6.

Alternative Diagnoses to Consider

A rash beginning behind the knees should prompt evaluation for:

1. Atopic Dermatitis/Eczema

• Flexural areas (behind knees, antecubital fossae) are classic locations
• Consider this first in the differential

2. Kawasaki Disease

• Rash is typically maculopapular, diffuse erythroderma, or erythema multiforme-like 10
• Primarily involves trunk and extremities
• Requires fever ≥5 days plus other criteria 10

3. Tickborne Rickettsial Diseases (RMSF, Ehrlichiosis)

• Rash begins on ankles, wrists, or forearms 3
• Can involve extremities and trunk 3
• Consider with fever, headache, and tick exposure history

4. Enteroviral Infections (Non-HFMD)

• Can cause various rash patterns 11
• May have lesions on hands, feet, and mouth but different distribution

Clinical Approach

If a child presents with rash behind the knees:

1. Obtain detailed history:

   • Fever pattern and duration
   • Oral symptoms or lesions
   • Progression of rash (where it started, how it spread)
   • Exposure history (sick contacts, outdoor activities, tick exposure)
   • Personal or family history of atopic dermatitis

2. Complete skin examination:

   • Check palms, soles, oral mucosa, buttocks
   • Look for vesicles, papules, or other morphology
   • Assess for flexural involvement suggesting eczema

3. If HFMD is still suspected despite atypical location:

   • Obtain throat swab and vesicle fluid for enterovirus PCR 4, 7
   • Consider stool sample for enterovirus testing 8

4. Management depends on confirmed diagnosis:

   • True HFMD requires only supportive care (hydration, pain control) 1
   • Resolution typically occurs within 10 days 6
   • Counsel families about nail changes (21% of cases) occurring 3 weeks post-infection 6

Key Pitfall to Avoid

Do not diagnose HFMD based solely on a rash behind the knees. The extensive literature on atypical HFMD presentations does not support this as a recognized pattern 4, 5, 7, 6. Misdiagnosis may lead to inappropriate infection control measures and missed alternative diagnoses requiring specific treatment.