Omnipresent infection occurring in infancy and childhood. Majority of cases are caused by human herpesvirus 6 (HHV-6); may be associated with other diseases including encephalitis


  • Acute infection of infants or very young children (1)
  • Causes a high fever followed by a skin eruption as the fever resolves (1)
  • Transmission via contact with salivary secretions or respiratory droplet (1)
  • Incubation period of 9 to 10 days (1)
  • System(s) affected: skin/exocrine, metabolic, gastrointestinal, respiratory, neurologic
  • Synonym(s): roseola infantum, exanthem subitum; pseudorubella; sixth disease; 3-day fever (1)

Pediatric Considerations
A disease of infants and very young children (2)


  • Predominant age
    • HHV-6
      • Infants and very young children (<2 years old) (3)
      • Peak age infection 6 to 9 months, rarely congenital or perinatal infection (1)
      • 95% of children have been infected with HHV-6 by 2 years of life.
    • HHV-7
      • Later childhood
      • Mean age of infection 26 months
      • >90% population with HHV-7 by 10 years (1)
  • Predominant sex: male = female (1)
  • No seasonal variance

Common—accounts for 20% ED visits for febrile illness among children 6 to 8 months (4)

  • Peak prevalence is between 9 and 21 months (3).
  • Nearly 100% population carrying HHV-6 by 3 years (1)
  • Approximately 20% patients with primary HHV-6 have roseola (4).

Etiology and Pathophysiology

  • HHV-6 and HHV-7 (2)
  • Majority of cases (60–74%) due to HHV-6
    • HHV-6B > HHV-6A (2)
    • HHV-6A seen in children in Africa
    • HHV-6 binds to CD46 receptors on all nucleated cells (2).
  • Primary infection typically through respiratory droplets or saliva
  • Congenital infection/vertical transmission occurs in 1% of cases (1).
    • Transplacental transmission
    • Chromosomal integration (clinical significance unknown)
  • Lifelong latent or persistent asymptomatic infection occurs after primary infection (1).
    • 80–90% of population intermittently sheds HHV-6/HHV-7 in saliva (2).
    • Patients are viremic from 2 days prior to fever until defervescence and onset of rash.
    • HHV-6 latency is also implicated in CSF (4).

HHV-6 is integrated into the chromosomes of 0.2–3.0% of the population. This leads to vertical transmission of the virus. Clinical significance of this is unknown (1).

Risk Factors

  • Female gender (3)
  • Having older siblings (3)
  • At-risk adults: immunocompromised (5)
    • Renal, liver, other solid organ, and bone marrow transplant (BMT) (3)
    • HHV-6 reactivation can occur in 1st week posttransplant (5). HHV-6 viremia occurs in 30–45% of BMT within the first several weeks after transplantation (4).
      • Usually asymptomatic (4)
      • Up to 82% of HHV-6 reactivation/reinfection in solid organ transplant (5)
  • Nonrisk factors (3)
    • Child care attendance
    • Method of delivery
    • Breastfeeding (HHV does not appear to pass through breast milk.)
    • Maternal age
    • Season



  • 3 to 5 days abrupt fever 102.2–104.0°F (39–40°C) not associated with a rash (1)
  • The child may be fussy during this prodrome (1,6).
  • Sudden drop of fever associated with appearance of rash (1)
    • Rash on trunk then spreads centrifugally mainly to neck, possibly also to peripheral extremities, and face
  • Diarrhea (3)
  • Mild upper respiratory symptoms (3)
  • Rhinorrhea (3)
  • Febrile seizure occurs in 13% of cases (1).

Physical Exam

  • Rash (exanthem subitum) (1)
    • Rose-pink macules and/or papules that blanch
    • First appears on the trunk then peripherally
    • May occur up to 3 days after fever resolves (1)
    • Fades within 2 days
    • Occurs in approximately 20% of patients in the United States (1)
  • Mild inflammation of tympanic membrane, pharynx, and/or conjunctiva (1,6)
  • Ulcers on soft palate and uvula (Nagayama spots) (1)
  • Cervical lymphadenopathy (1)
  • Periorbital edema (2)

Differential Diagnosis

  • Enterovirus infection
  • Adenovirus infection (1)
  • Epstein-Barr virus
  • Fifth disease—parvovirus B19
  • Rubella (1)
  • Scarlet fever (1)
  • Drug eruption (1)
  • Measles (1)

Diagnostic Tests & Interpretation

  • Primarily a clinical diagnosis not requiring laboratory or radiologic testing (1)[C]
  • Tests often cannot differentiate latent or active disease (1)[C].
  • Specific diagnosis only necessary in severe cases, unclear diagnosis where more serious disease needs to be ruled out, or if considering antiviral therapy (1)[C]

Initial Tests (lab, imaging)
  • HHV-6 and HHV-7 by PCR (1,5)[C]
    • Serum, whole blood, CSF, or saliva
    • Becoming more widely available
    • Not required in non-immunocompromised individuals
  • HHV-6 IgM immunofluorescence (1)
  • Diagnostic for acute infection
    • Spike seen in 1st week of illness
  • HHV-6 IgG immunofluorescence (1)
    • Check at diagnosis and then 2 weeks later.
    • Use with IgM to show primary infection.
    • Negative initial test and rise on follow-up suggest primary infection.
  • Viral culture (5)
    • Rarely done
    • No clinical use (very time-consuming)
  • Other laboratory findings (1)
    • Decreased total leukocytes, lymphocytes, and neutrophils
    • Elevated transaminases
    • Thrombocytopenia
Diagnostic Procedures/Other
  • Urine culture: to rule out UTI as source of fever (2)
  • Chest x-ray (CXR): if a child has respiratory symptoms


No treatment necessary, resolves without sequelae (1)[C]

General Measures

  • Symptomatic relief including antipyretics (1)[C]
  • Hydration (1)[C]


First Line
  • No specific first-line treatment in immunocompetent hosts beyond supportive measures (2)[C]
    • Antivirals are not recommended in immunocompetent.
  • No approved antiviral treatment in immunocompromised (2)[C]
  • Second-line IV ganciclovir, cidofovir, foscarnet tested in vitro studies in stem cell transplant patients
    • HHV-6B susceptible: ganciclovir and foscarnet (5)[C]
    • HHV-6A and HHV-7 are more resistant to ganciclovir (5).
  • Antivirals suggested in individual cases of encephalitis (associated with reactivation of HHV-6) (5)
  • In bone marrow and stem cell transplant recipients receiving immunosuppression, ganciclovir prophylaxis is effective in preventing reactivation of HHV-6 (6)[B].

Ongoing Care

Follow-up Recommendations

Patient Monitoring
  • During febrile prodrome, monitor for dehydration.
  • None after typical rash appears and fever resolves
  • Mean duration of illness is 6 days (4).
  • If febrile seizures occur, they will cease after fever subsides and will not likely recur (4).
  • Symptomatic reactivation in immunocompromised (1)


Encourage fluids.

Patient Education

  • Parental reassurance that this is usually a benign, self-limited disease (1)
  • There is no specific recommended period of exclusion from out-of-home care for affected children.
  • Patient is viremic a few days prior to fever until time of defervescence and rash onset.


  • Course: acute, complete recovery without sequelae (1)
  • Reactivation in immunocompromised patients is common (4).


  • Febrile seizures
    • 13% patients with roseola (1,6)
    • Accounts for 1/3 of primary seizures in children <2 years old (1)
  • Medication hypersensitivity syndromes (drug reaction with eosinophilia and systemic symptoms) (2)
  • Reactivation can occur in transplant patients, HIV-1 infection, and other immunocompromised individuals (4).
  • Meningoencephalitis occurs in immunocompetent and in immunosuppressed patients (4); poor association with multiple sclerosis (4)
  • Pityriasis rosea (1)
  • Possible association with progressive multifocal leukoencephalopathy (4)

Additional Reading

  • Ablashi DV, Devin CL, Yoshikawa T, et al. Review part 3: human herpesvirus-6 in multiple non-neurological diseases. J Med Virol. 2010;82(11):1903–1910. [PMID:20872717]
  • Caselli E, Di Luca D. Molecular biology and clinical associations of roseoloviruses human herpesvirus 6 and human herpesvirus 7. New Microbiol. 2007;30(3):173–187. [PMID:17802896]
  • Dockrell DH, Smith TF, Paya CV. Human herpesvirus 6. Mayo Clin Proc. 1999;74(2):163–170. [PMID:10069356]
  • Dyer JA. Childhood viral exanthems. Pediatr Ann. 2007;36(1):21–29. [PMID:17269280]
  • Evans CM, Kudesia G, McKendrick M. Management of herpesvirus infections. Int J Antimicrob Agents. 2013;42(2):119–128. [PMID:23820015]
  • Fölster-Holst R, Kreth HW. Viral exanthems in childhood—infectious (direct) exanthems. Part 1: classic exanthems. J Dtsch Dermatol Ges. 2009;7(4):309–316. [PMID:18803578]
  • Huang CT, Lin LH. Differentiating roseola infantum with pyuria from urinary tract infection. Pediatr Int. 2013;55(2):214–218. [PMID:23190314]
  • Leach CT. Human herpesvirus-6 and -7 infections in children: agents of roseola and other syndromes. Curr Opin Pediatr. 2000;12(3):269–274. [PMID:10836165]
  • Lowry M. Roseola infantum. Pract Nurse. 2013;43:40–42.
  • Stoeckle MY. The spectrum of human herpesvirus 6 infection: from roseola infantum to adult disease. Annu Rev Med. 2000;51:423–430. [PMID:10774474]
  • Vianna RA, de Oliveira SA, Camacho LA, et al. Role of human herpesvirus 6 infection in young Brazilian children with rash illnesses. Pediatr Infect Dis J. 2008;27(6):533–537. [PMID:8449066]



  • B08.20 Exanthema subitum [sixth disease], unspecified
  • B08.21 Exanthema subitum [sixth disease] due to human herpesvirus 6
  • B08.22 Exanthema subitum [sixth disease] due to human herpesvirus 7
  • B09 Unsp viral infection with skin and mucous membrane lesions


  • 057.8 Other specified viral exanthemata
  • 058.10 Roseola infantum, unspecified
  • 058.11 Roseola infantum due to human herpesvirus 6
  • 058.12 Roseola infantum due to human herpesvirus 7


  • 402419007 Roseolar erythema
  • 402902002 Roseola infantum (HHV 6)
  • 402903007 Roseola infantum (HHV 7)
  • 54385001 Exanthema subitum

Clinical Pearls

  • Roseola infection should be suspected if an infant or young child presents with a high temperature without other clinical findings.
  • As the fever abates, a macular rash will be seen on the trunk, with eventual spread to the face and extremities in 20% of patients.
  • Roseola is a clinical diagnosis, and laboratory testing is not necessary for most children with classic presentation.
  • For atypical presentations, complications, and immunocompromised hosts, several laboratory tools are available, including serologic testing for antibody, viral PCR testing, and viral culture.
  • Infection is typically self-limiting and without sequelae.
  • Usually, only symptomatic treatment is needed.
  • Consider prophylaxis in patients undergoing bone marrow or stem cell transplant and receiving immunosuppressive therapy.


Jeffrey D. Quinlan, MD, FAAFP


  1. Stone RC, Micali GA, Schwartz RA. Roseola infantum and its causal human herpesviruses. Int J Dermatol. 2014;53(4):397–403.  [PMID:24673253]
  2. Wolz MM, Sciallis GF, Pittelkow MR. Human herpesviruses 6, 7, and 8 from a dermatologic perspective. Mayo Clin Proc. 2012;87(10):1004–1014.  [PMID:22819486]
  3. Zerr DM, Meier AS, Selke SS, et al. A population-based study of primary human herpesvirus 6 infection. N Engl J Med. 2005;352(8):768–776.  [PMID:15728809]
  4. Caserta MT, Mock DJ, Dewhurst S. Human herpesvirus 6. Clin Infect Dis. 2001;33(6):829–833.  [PMID:11512088]
  5. Le J, Gantt S; for AST Infectious Diseases Community of Practice. Human herpesvirus 6, 7 and 8 in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):128–137.  [PMID:23465006]
  6. Tokimasa S, Hara J, Osugi Y, et al. Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in allogeneic stem cell transplantation. Bone Marrow Transplant. 2002;29(7):595–598.  [PMID:11979309]

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