Roseola infantum (exanthem subitum, sixth disease) is caused primarily by human herpesvirus type 6 (HHV-6), and by HHV-7 in 10% to 30% of cases. HHV-6 and HHV-7 are large, enveloped double-stranded DNA viruses that are members of the herpesvirus family. They infect mature mononuclear cells and cause a relatively prolonged (3 to 5 day) viremia during primary infection. They can be detected in the saliva of healthy adults, which suggests, as with other herpes-viruses, the development of lifelong latent infection and intermittent viral shedding.
Transplacental antibody protects most infants until 6 months ofage. The incidence of infection increases as maternally derivedantibody levels decline. By 12 months of age, approximately60% to 90% of children have antibodies to HHV-6, and essentially all children are seropositive by 2 to 3 years of age. Thevirus is likely acquired from asymptomatic adults who periodically shed these viruses. HHV-6 is a major cause of acute febrileillnesses in infants and may be responsible for 20% of visits tothe emergency department for children 6 to 18 months of age.
Roseola is characterized by high fever (often >40° C) with an abrupt onset that lasts 3 to 5 days. A maculopapular, rose-colored rash erupts coincidentally with defervescence, although it may be present earlier. The rash usually lasts 1 to 3 days but may fade rapidly and is not present in all infants with HHV-6 infection. Upper respiratory symptoms, nasal congestion, erythematous tympanic membranes, and cough may occur. Gastrointestinal symptoms are described. Most children with roseola are irritable and appear toxic. Roseola is associated with approximately one third of febrile seizures. Roseola caused by HHV-6 and HHV-7 is clinically indistinguishable, although HHV-6-associated roseola typically occurs in younger infants. Reactivation of HHV-6 following bone marrow transplantation may result in bone marrow suppression, hepatitis, rash, and encephalitis.
Routine laboratory findings are nonspecific and do not aid in diagnosis. Encephalitis with roseola is characterized by pleocytosis (30 to 200 cells/mm3) with mononuclear cell predominance, elevated protein concentration, and normal glucose concentration. Serologic testing showing a fourfold rise in acute and convalescent sera or documentation of HHV-6 DNA by PCR in the cerebrospinal fluid is diagnostic.
The pattern of high fever for 3 to 5 days without significant physical findings followed by onset of rash with defervescence of fever is characteristic. Many febrile illnesses may be easily confused with roseola during the preeruptive stage. Serious infections must be excluded, although most children are alert, behave normally, and continue with their usual daily activities.
There is no specific therapy for roseola. Routine supportive care includes maintaining adequate hydration and antipyretics. In immunocompromised hosts, use of ganciclovir or foscarnet can be considered.
The prognosis for roseola is excellent. A few deaths have been attributed to HHV-6, usually in cases complicated by encephalitis or virus-associated hemophagocytosis syndrome.
There are no guidelines for prevention of roseola.