Two common pediatric viral exanthems: roseola features high fever that breaks as rash appears, while HFM produces oral ulcers with vesicles on palms and soles.
Also known as: roseola infantum, exanthem subitum, sixth disease, HHV-6, HHV-7, hand-foot-mouth disease, HFMD, coxsackievirus A16, enterovirus 71
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Risk factors
- Age 6 months-3 years (roseola)
- Daycare, summer/fall transmission (HFMD)
- Immunocompromise (severe or atypical HHV-6 reactivation; severe HFMD)
- Crowded settings
Pathophysiology
HHV-6 infects CD4 T cells and establishes lifelong latency; primary infection produces febrile viremia followed by an immune-complex-mediated rash as virus is cleared. Coxsackievirus A16 and EV71 are enteroviruses (RNA, Picornaviridae) that infect oral and skin epithelium via fecal-oral and respiratory routes.
Clinical presentation
Symptoms
- Roseola: abrupt high fever (39-40 °C) for 3-5 days in an otherwise well-appearing toddler; fever defervesces and a pink macular/maculopapular rash erupts on the trunk, spreading to neck and extremities, lasting hours to 2 days
- Roseola can present with febrile seizures during the fever phase
- HFMD: 1-2 day prodrome of fever, sore throat, anorexia; followed by oral vesicles and ulcers on the tongue, buccal mucosa, soft palate, and 5-10 mm tender vesicles on palms, soles, buttocks
- Self-limited 7-10 days
Signs / physical exam
- Roseola: rose-pink macules and papules sparing the face; Nagayama spots (papules on the soft palate and uvula)
- Erythematous tympanic membranes, mild cervical and postauricular adenopathy
- HFMD: shallow yellow-gray oral ulcers with red halos; oval or football-shaped vesicles on hands and feet aligned with skin tension lines
- Onychomadesis (nail shedding) weeks after coxsackievirus A6 HFMD
Classic findings
Roseola: high fever that breaks as the rash appears. HFMD: oral ulcers PLUS vesicles on palms and soles.
Differential diagnosis
- Measles — Three Cs, Koplik spots, severe prodrome before rash
- Rubella — Posterior auricular nodes, rash without preceding high fever
- Drug-induced rash — Antibiotic given for the fever, rash appears 1-2 weeks later; classic in EBV mononucleosis exposed to ampicillin
- Herpes simplex stomatitis — Gingivostomatitis without acral vesicles
- Aphthous stomatitis — Oral ulcers without systemic illness or hand/foot lesions
- Varicella — Generalized vesicles in multiple stages, including scalp and trunk
Diagnostic workup
Diagnostic criteria
Roseola: high fever 3-5 days in 6 mo-3 yr child followed by rose-pink rash on defervescence. HFMD: oral ulcers plus vesicles on palms/soles.
Labs
- Both diagnoses are clinical
- HHV-6 PCR or serology rarely needed except in immunocompromised hosts
- Enterovirus PCR (throat, stool, or vesicle swab) in severe or atypical HFMD
- CBC: mild leukopenia or normal
Imaging
- Not required for typical disease
- Neuroimaging and LP for HFMD with neurologic signs (EV71 brainstem encephalitis)
Treatment
First-line
- Supportive care for both: hydration, antipyretics (acetaminophen, ibuprofen)
- HFMD: topical anesthetic mouth rinses (e.g., 'magic mouthwash'), soft cool foods, AVOID acidic and salty foods
- Hand hygiene and contact precautions to reduce spread
- Reassure parents that febrile seizures during roseola are usually simple and benign
Severe / atypical HFMD (EV71)
- Hospitalize if neurologic signs (myoclonic jerks, ataxia, cardiopulmonary instability)
- Supportive ICU care; IVIG considered in severe disease
Immunocompromised with HHV-6 reactivation
- Ganciclovir or foscarnet for end-organ disease (encephalitis, pneumonitis)
- Reduce immunosuppression if feasible
Second-line / adjunct
- Counsel families to avoid aspirin in any febrile child (Reye risk)
Complications
- Roseola: febrile seizures, encephalitis (rare), reactivation in immunocompromised (graft dysfunction post-transplant)
- HFMD: dehydration from poor oral intake; onychomadesis weeks later (coxsackievirus A6); EV71 brainstem encephalitis, myocarditis, pulmonary edema, paralysis
- Atypical HFMD in adults with eczema can mimic eczema coxsackium with widespread vesicles
PANCE pearls
- Roseola: 'fever breaks, rash appears.' Think HHV-6 in a febrile toddler whose rash appears as the fever resolves.
- HFMD vesicles align along skin tension lines on the dorsa of hands and lateral feet — a useful visual clue.
- EV71 HFMD can cause life-threatening brainstem encephalitis; admit any HFMD patient with neurologic signs.
- Nail shedding (onychomadesis) 4-8 weeks after HFMD is a benign late finding worth recognizing.
- Both illnesses are self-limited and rarely require antivirals in immunocompetent children.
References
- AAP Red Book — American Academy of Pediatrics Red Book — Human Herpesvirus 6 and 7; Enterovirus chapters
- CDC — CDC Hand, Foot, and Mouth Disease Clinician Information
- WHO — WHO Western Pacific Region Guidelines for Enterovirus 71
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