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.
Try two board-style Roseola (HHV-6) and Hand-Foot-Mouth Disease questions
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Question 1Infectious DiseaseMedium
An 18-month-old boy is brought to clinic with 2 days of fever, fussiness, and decreased oral intake. He attends daycare, where several children have been sick. Vital signs: temperature 38.6 C, otherwise normal. Exam shows multiple shallow yellow ulcers on the tongue, buccal mucosa, and soft palate, along with several gray-white vesicles on erythematous bases on the palms, soles, and buttocks. The remainder of the exam is unremarkable. Which of the following is the most likely diagnosis?
AHerpangina
BHand, foot, and mouth disease
CHerpetic gingivostomatitis
DVaricella
Reveal answer & full explanation
Correct answer: B — Hand, foot, and mouth disease
AHerpangina
BHand, foot, and mouth disease✓
CHerpetic gingivostomatitis
DVaricella
Why Hand, foot, and mouth disease is correct
Hand, foot, and mouth disease (HFMD) is most commonly caused by coxsackievirus A16, and increasingly by enterovirus 71 and coxsackievirus A6
Highly contagious among young children in daycare settings
Presents with low-grade fever followed by painful oral ulcers (especially on the tongue, buccal mucosa, and soft palate) plus a characteristic vesicular exanthem on the palms, soles, and buttocks
Disease is self-limited within 7–10 days; management is supportive with hydration and analgesia
Why the others are wrong
C) Herpetic gingivostomatitis — HSV-1 infection causing painful clustered vesicles and ulcers on the gingiva and anterior oral cavity with prominent gingival inflammation; no palmar or plantar lesions
D) Varicella — diffuse pruritic vesicles in different stages of evolution on the trunk, face, and scalp; oral lesions can occur but the rash distribution is generalized rather than acral
A) Herpangina — also a coxsackievirus illness but limited to posterior oropharyngeal vesicles/ulcers (soft palate, tonsillar pillars) without the palm/sole/buttock exanthem
Question 2Infectious DiseaseMedium
A 14-month-old boy is brought in for 4 days of fever to 40°C. He has been fussy but feeding and otherwise well-appearing, with no cough, coryza, or rash during the febrile days. This morning the fever resolved and a blanching pink macular rash erupted on his trunk, then spread to the neck and proximal extremities while sparing the face. Examination shows mild posterior cervical adenopathy and erythematous tympanic membranes. Which of the following complications is this child most likely to develop?
ASubacute panencephalitis
BAcute glomerulonephritis
CCoronary artery aneurysm
DSimple febrile seizure
Reveal answer & full explanation
Correct answer: D — Simple febrile seizure
ASubacute panencephalitis
BAcute glomerulonephritis
CCoronary artery aneurysm
DSimple febrile seizure✓
Why Simple febrile seizure is correct
The illness described is roseola (exanthem subitum, sixth disease) from HHV-6: 3-5 days of high fever in a well-appearing 6 mo-3 yr toddler, with a rose-pink trunk-first rash that erupts as the fever breaks and spares the face.
Febrile seizures are the most common complication of roseola, occurring during the high-fever viremic phase; HHV-6 accounts for a substantial fraction of first febrile seizures in this age group.
These are typically simple febrile seizures and are benign and self-limited; parents should be reassured and care is supportive.
Why the others are wrong
Subacute panencephalitis (subacute sclerosing panencephalitis) is a rare, fatal late complication of measles, not roseola; this child had no measles prodrome (cough, coryza, conjunctivitis, Koplik spots) and the rash appeared after, not during, the fever.
Coronary artery aneurysm is the feared complication of Kawasaki disease, which requires 5 or more days of fever plus mucocutaneous criteria (conjunctivitis, mucositis, extremity changes, cervical node 1.5 cm or larger); this well-appearing child with a defervescence rash does not fit.
Acute glomerulonephritis here would point to poststreptococcal disease, which follows group A streptococcal pharyngitis or impetigo, not an HHV-6 viral exanthem; there is no antecedent strep infection.
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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)
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