Roseola - Exanthem Subitum

Wisconsin Viral Research Group, Ltd.

Physician's Corner: Roseola

Primary HHV-6 Infections: Exanthem Subitum

In 1988, it was discovered that HHV-6 was the cause of the early childhood disease exanthem subitum (ES) also known as roseola infantum. Ninety percent of young children become infected with HHV-6 by the age of two years. The virus is purported to be transmitted through contact with saliva from a caregiver with an active infection. ES is characterized by high fever for several days, followed by fever defervescence and the appearance of a rash of one to two days' duration. Rash, the classic symptom of ES, may be present in only 10 to 40% of children with primary HHV-6 infection.

Most primary HHV-6 infections are self-limiting and without serious consequences. However, complications of primary HHV-6 infection are not uncommon with the most serious and frequent complications being convulsions or seizures. During primary infection with the virus, a variable but significant proportion of children will present with CNS disturbances in the form of febrile seizures suggesting a predilection of HHV-6 for neural tissue. In studies of children admitted to hospital emergency rooms for acute febrile illness, central nervous system disorders were associated with primary HHV-6 infection in 25% of the cases. HHV-6 DNA can be found in cerebrospinal fluid samples from children experiencing convulsions concurrently with acute HHV-6 infection demonstrating direct infection of the brain by the virus.

Primary HHV-6 infection is acquired via the eyes and nose through contact with infectious saliva, and the infection is generally limited to the upper respiratory tract (nose and throat). While primary infection with HHV-6 invariably begins as an upper respiratory tract infection, lower respiratory tract disease is not unusual and the virus is likely to be found in the context of clinically significant pneumonia. In fact, studies have shown that progression to a clinically significant lower respiratory tract infection, including pneumonia, occurs in about 15% of children seeking medical treatment for acute infection with HHV-6.

Another frequently observed and serious clinical manifestation of primary HHV-6 infection has been low WBC and platelet counts. Significant depression of multiple peripheral blood cell elements during primary infection has now been shown to be the rule rather than the exception, and this finding implicates HHV-6 in the bone marrow suppression observed during the acute infection. In a major prospective study evaluating the complications of HHV-6 infections in children, investigators reported that children with HHV-6 illness had significant decreases in peripheral blood leukocytes (8900 vs. 14,300 per ul), lymphocytes (3400 vs. 5300 per ul) and neutrophils (4400 vs. 7700) per ul). ¹

Finally, the possibility that HHV-6 could cause loss of selected T lymphocyte populations, e.g. the CD4+ T lymphocyte during the acute phase of the infection, suggests a definite tropism of the virus for this cell population.

Thus, as observed in the natural course of the primary infection with HHV-6, the biologic repertoire of HHV-6 includes the capacity for neuroinvasion resulting in seizures, respiratory infection resulting in pneumonitis, the ability to suppress bone marrow function, and the potential for selectively targeting of the CD4+ T lymphocyte.