Infectious Disease · PANCE / PANRE

Roseola (HHV-6) and Hand-Foot-Mouth Disease (Coxsackievirus)

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

Overview

Roseola (exanthem subitum, sixth disease) is a febrile illness of infants and toddlers caused by human herpesvirus 6 (and less often HHV-7), notable for a high fever that breaks just before a rose-colored rash appears. Hand-foot-mouth disease (HFMD) is a viral exanthem in young children caused chiefly by coxsackievirus A16 and enterovirus 71, with oral enanthem and acral vesicles.

Epidemiology

Roseola: nearly universal infection by age 2-3; peak 6-15 months. HFMD: outbreaks in summer and fall in daycare centers; enterovirus 71 outbreaks in Asia have caused severe neurologic disease.

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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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