Human Herpesvirus 6 

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jun 23, 2010
 

Background

Human herpesvirus 6 (HHV-6) is the virus that most commonly causes the childhood disease roseola. It was first isolated in 1986. Two genetically distinct variants have been discovered: human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B). HHV-6B has been associated with a variety of viral illnesses, including exanthem subitum (roseola infantum), mononucleosis syndromes, focal encephalitis, and pneumonitis.[1] The virus is spread through saliva and possibly by genital secretions. This virus shows the closest homology with cytomegalovirus and human herpesvirus 7 (HHV-7).

HHV-6 infection in infants is the most common cause of fever-induced seizures. Infection in adults is seen primarily in immunocompromised hosts who have undergone solid organ transplants or in those with HIV infection.[2, 3] Reactivation of latent HIV infection attributable to HHV-6 infection has been reported.[4] No prophylaxis or treatment for infection with HHV-6 presently exists. The great majority of HHV-6 infections are silent or appear as a general mild febrile illness.

The child with HHV-6 usually does not appear seriously ill during this disease. HHV-6 infection is much more serious in adults and can lead to organ involvement (usually presenting as gastrointestinal symptoms or hepatitis), encephalitis, or death.

To elucidate the role of HHV-6 and HHV-7 in pityriasis rosea (PR), their DNA load in plasma, peripheral blood mononuclear cells (PBMCs), and tissues was evaluated using a calibrated quantitative real-time polymerase chain reaction assay.[5] In addition, HHV-6– and HHV-7–specific antigens in skin were evaluated by immunohistochemistry and anti–HHV-7 neutralizing activity using a syncytia-inhibition test. HHV-6 and HHV-7 DNA were found in 17% and in 39% of PR plasmas, respectively, but in no controls. HHV-6 levels in PBMCs were not higher in PR patients than in controls. HHV-6 and HHV-7 antigens were detected only in PR skin (17% and 67% of patients analyzed, respectively), presumably indicating a productive infection. These and other data strongly suggest a causal association between PR and active HHV-7 or, to a lesser extent, HHV-6 infection.

The reactivation of herpesviruses, including HHV-6 and EBV (Epstein-Barr virus), is linked with a potentially serious drug eruption known as DRESS (drug reaction with eosinophilia and systemic symptoms).[6] A report of high-level HHV-6 viremia associated with the onset of Stevens-Johnson syndrome suggests an association.[7]

Related eMedicine articles include Human Herpesvirus Type 6 (from Infectious Diseases section), Roseola Infantum, Encephalitis, and Pityriasis Rosea.

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Pathophysiology

Human herpesvirus 6 (HHV-6) infection in children most commonly leads to roseola infantum, also known as exanthem subitum. Children aged 6 months to 3 years are most at risk and contract the virus from saliva. It replicates in leukocytes and in salivary glands and then spreads throughout the body. The virus is predominantly T lymphotropic and is believed to invade the CNS, which may lead to such CNS complications as seizures and encephalitis. The incubation period is thought to be between 5-15 days.

Serologic studies demonstrate that HHV-6 infects approximately 90% of children by age 2 years.[8] A cohort was prospectively studied. HHV-6 was found to be acquired in infancy, to usually be symptomatic, and to often result in a medical evaluation. However, only a minority of these patients developed roseola or febrile seizures with primary HHV-6 infection. Older siblings appeared to be a source of HHV-6 transmission.

Time course characteristics of HHV-6–specific cellular immune response and natural killer cell activity in patients with exanthema subitum were studied.[9] Natural killer cells seem to play a major role in resolving acute-phase HHV-6 infection, while specific lymphocyte activity develops later. The lymphoproliferative response to phytohemagglutinin ratios was interpreted as implying that HHV-6 infection has some impact on host T-cell immunity during the course of exanthema subitum.

HHV-6 chromosomal integration in immunocompetent patients was found to result in high levels of viral DNA in blood, sera, and hair follicles.[10] These characteristically high HHV-6 DNA levels in chromosomal integration should be considered in establishing laboratory diagnosis methods.

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Epidemiology

Frequency

United States

Evidence of past human herpesvirus 6 (HHV-6) infection is found in most people, but initial infection usually occurs within the first 2 years of life. Roseola is estimated to affect as many as 30% of all children and is most common in spring and fall.

International

Human herpesvirus 6 (HHV-6) has a worldwide distribution. The predominant form of HHV-6 was found to be variant A in infant infections in an HIV-1 endemic region of sub-Saharan Africa.[11] HHV-6B is the predominant infant infection in the United States, Europe, and Japan, where HHV-6A appears to be rare.

Mortality/Morbidity

Human herpesvirus 6 (HHV-6) infection is usually asymptomatic. Even when HHV-6 leads to roseola, it is a mild illness in children who are immunocompetent. It usually resolves without any treatment; however, in some rare cases, patients who are immunocompetent may develop additional symptoms, including respiratory distress, seizures, and multiorgan involvement. It is very rarely fatal.

  • In adults who are immunosuppressed (eg, those with AIDS), HHV-6 is a major source of morbidity and mortality, especially in those who do not take antiretroviral therapy. In these patients, disseminated organ involvement and death can occur.
  • In adults who are immunosuppressed because of undergoing a transplant, HHV-6 infection may cause multiorgan system involvement, accelerate organ rejection, and lead to death.
  • In adults who are immunocompetent, primary infection or reactivation with HHV-6 can produce a mononucleosislike illness and, more rarely, severe disease, including encephalitis.

Race

No increased incidence exists in any particular race. HHV-6 infection is nearly universal.

Sex

Both males and females are affected equally.

Age

The most common age group affected by roseola is children aged 6 months to 3 years. The average age is 9 months. This occurrence is thought to coincide with decreasing maternal antibodies, which leave the child more susceptible to infection. Most people are infected with HHV-6 by age 2 years.

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Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Cris Jagar, MD  Staff Physician, Department of Psychiatry, Saint Vincent Catholic Medical Centers

Disclosure: Nothing to disclose.

Ewa Koziorynska, MD  Assistant Professor of Neurology, Comprehensive Epilepsy Center, State University of New York Downstate Medical Center

Ewa Koziorynska, MD is a member of the following medical societies: Sigma Xi

Disclosure: none None None

Specialty Editor Board

Franklin Flowers, MD  Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, University of Florida College of Medicine

Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey Meffert, MD  Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society

Disclosure: Nothing to disclose.

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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