Exanthema subitum is a viral illness caused by human herpes virus 6 (HHV 6) and less commonly by HHV 7. The HHV 6 and HHV 7 are together referred as the Roseolovirus. A disease primarily of childhood, it is also known as roseola, roseola infantum, rose rash of infants, sixth disease, three-day fever and baby measles. The disease initially presents in childhood and the secondary infection is common in immunocompromised individuals.
Exanthema subitum occurs in children less than 2 years of age, with most patients presenting in infancy. After an incubation period of 5-15 days, the classical presentation is that of high-grade fever followed by the appearance of a morbilliform rash.
The fever usually lasts for 3-5 days, with temperatures ranging from 39.5-40.5 degrees celsius  . The baby is usually alert and active without any specific foci of infection . Febrile seizures may be seen in 15% of cases. Lymphadenopathy in the cervical and posterior auricular region may also be seen. Encephalitis and hepatitis are rare manifestations. During this phase, the examination may not reveal a lot of findings. Upper respiratory tract, gastrointestinal and CNS signs are rare at this stage.
The disappearance of fever coincides with the development of a mild morbilliform rash, seen most commonly on the chest and abdomen and rarely, on the face and extremities. The rash may vary in appearance from a small pink papule to a more generalized maculopapular exanthema. The rash usually lasts for a few hours to 2 days and may only be seen in 30% of cases infected with human herpes virus 6 .
Two-thirds of patients may show a characteristic enanthem (Nagayama's spots) on the soft palate and uvula. They usually take the form of erythematous papules and occur most commonly on the 4th day of illness.
HHV-6 often remains latent in patients with a well-functioning immune system. Immunocompromised patients, however, have a more abrupt onset of disease, with the disease spreading to the CNS and other organs  .
Hepatic dysfunction is rarely noted in patients. A few adults, with a past history of HHV-6 infection, may show reactivation of virus with clinical features of mononucleosis . Few patients have been reported with minimal signs and symptoms of the disease despite acquiring HHV-6 infection .
The diagnosis is usually clinical and a high degree of suspicion is to be held in children from 6 months-3 years with the classical clinical presentation. Further tests are rarely required. Confirmation of diagnosis may be done through serology or culture.
Routine blood tests, including a CBC, blood culture, cerebrospinal fluid (CSF) studies and urinalysis, may be done to rule out other causes of fever . Further testing to exclude other etiologies of seizures may be necessary for some patients.
Serological tests for herpes virus include virus isolation studies and detection of viral DNA from mononuclear blood cells. Antibodies to the different variants of human herpes virus 6 (HHV6A and HHV6B) may be detected by an immunoblot assay .
Histology of affected organs shows a characteristic ballooning of cells.