Human Herpes Virus 6 and Roseola

Classic Case: The mother of a 7 month male brought her child to the office one day ago. The child had a temperature of 39.4 and a normal physical examination. She calls today and states that the child has a rash on the trunk, but the fever is gone. What is the most likely diagnosis?

Human Herpes Virus-6 (HHV-6) is one of the causative agents of the common childhood disease, Roseola. Roseola is classically characterized by 3-5 days of high fever that resolves abruptly and is followed by a characteristic rash. HHV-6 has been associated with other clinical presentations in children, including fever without a rash, febrile seizures, meningoencephalitis, hepatitis, medication hypersensitivity syndromes, and infections in children who are immunocompromised/transplant recipients. 

Epidemiology

  • ​Most newborns receive transplacental protective antibodies; this lasts for about 3 months.
  • Roseola is a disease of young children, most often between 7-13 months.
  • By 2 years of age, 90% of children will be infected by the virus and show an antibody response. 

Pathogenesis

  • HHV-6 is an enveloped, double-stranded DNA virus. 
  • The incubation period is thought to be approximately 9 days. 
  • The most common route of HHV-6 transmission is thought to be from close household contacts via asymptomatic shedding of the virus. Perinatal transmission is also possible. 
  • Little is known about the specifics of the pathogenesis of HHV-6 infection. Most cases occur sporadically without a known exposure. The duration of viral shedding is thought to be life-long. 

Clinical Presentations

Roseola

  • Three to five days of high fever (may exceed 40 degrees C)
  • Irritability can occur, but many children are otherwise alert, active and quite well-appearing. 
  • Other signs and symptoms may include: lymphadenopathy, erythematous tympanic membranes, anorexia, and upper respiratory symptoms.
  • The fever resolves abruptly and is followed by the characteristic rash, which starts on the neck and trunk and spreads to the face and extremities. The rash usually lasts 1-2 days, but can persist for even shorter periods of time (2-4 hours). The rash is not usually itchy. 
  • Roseola is usually self-limited and quite benign. 

Other Manifestations of HHV-6

  • Fever: HHV-6 can present as a febrile illness without a rash. 
  • Febrile seizures: HHV-6 has been associated with febrile seizures.
  • Meningoencephalitis: Encephalitis can occur as a complication of roseola or as part of a primary HHV-6 infection without a rash. 
  • Congenital HHV-6: Congenital HHV-6 is often asymptomatic. Neonates do rarely develop hepatitis, myocarditis, pneumonitis, a mononucleosis-like syndrome, and a variety of other presentations. 
  • Medication hypersensitivity syndromes: HHV-6 has been described as a possible contributing factor in DRESS syndrome and other hypersensitivity reactions. 
  • Immunocompromised children, Children with cancer, and Transplant Recipients: Reactivation syndromes and febrile illnesses caused by HHV-6 have been described in children who are immunocompromised. 

Diagnosis

  • Classic roseola is usually diagnosed based on clinical history and physical exam. Laboratory analysis is rarely required. 
  • For atypical presentations, laboratory tools are available to aid in diagnosis. That said, it should be noted that HHV-6 persists in many children following the resolution of the illness, and may reactivate periodically in otherwise asymptomatic children. This tendency complicates matters. 
    - HHV-6 can be cultured from peripheral RBCs
    - Monoclonal antibodies can be used to detect HHV-6 
    - Qualitative and quantitative DNA PCR tests exist, but cannot always distinguish between active and latent infections

Treatment 

  • Most of the time, HHV-6 infections are self-limited and benign. Treatment is supportive. 
  • Some reports suggest that anti-viral therapies may be useful in some patients, but more data is required at this time. 

References

  1. Asano Y et al. Clinical Features of Infants with Primary Human Herpes Virus Six Infection. Pediatrics. 1994;93:104.  
  2. Hall, Caroline Breese. Herpesvirus VI: New light on an old childhood exanthem. Contemporary Pediatrics. January, 1996
  3. Hall, Caroline Breese. et. al. Human Herpesvirus-6 Infection in Children. A Prospective Study of Complications and Reactivation. NEJM. August 18, 1994
  4. Prober C. Sixth Disease and the Ubiquity of Human Herpesviruses. NEJM Feb 24, 2005. 
  5. Zerr D. A Population-Based Study of Primary Human Herpesvirus 6 Infection. NEJM. Feb 24, 2005. 

Back to Table of Contents