Fever for several days in an infant who still looks well, then a rash as the fever breaks: that sequence is roseola infantum, also called sixth disease or exanthem subitum, and it is both the most recognisable and the mildest of the six classic exanthems. The fever is frightening and the illness is not, which is why the pattern is worth recognising — the alternative is a sequence of investigations for a febrile infant who does not need them.
The virus
Roseola is caused by human herpesvirus 6 (HHV-6, predominantly the HHV-6B variant), a double-stranded DNA virus in the Herpesviridae family. The alternative name sixth disease comes from the historical numbering of the classic childhood exanthems, in which roseola infantum is the sixth; HHV-6 also happens to be the sixth human herpesvirus to be identified, which is a coincidence rather than the origin of the name. Like the other herpesviruses it establishes lifelong latency after primary infection, persisting in a dormant state, but roseola is the illness of primary infection. Reactivation matters only in immunocompromised hosts.
Epidemiology
The age band is narrow and useful: primary infection is most common between 6 months and 2 years, and most children have been infected by the age of 2. Cases under 3 months are rare because maternal antibody is still present, and cases after 3-4 years are uncommon because the child has already seroconverted, that is, developed antibodies from an earlier infection. Transmission is respiratory, through droplets and saliva, and most cases occur sporadically without an identified exposure. There is no strong seasonality.
Clinical course
The incubation period is roughly 5-15 days. The illness then follows two distinct steps.
Fever, with few other findings. The child develops a sudden high fever, often 39-40 °C, that lasts 3-5 days. The striking feature is the mismatch between the height of the fever and the child’s other symptoms: a mildly injected pharynx, mild coryza, irritability and poor sleep, sometimes diarrhoea, and enlarged laterocervical or occipital lymph nodes, but an otherwise unremarkable examination. The fever may respond poorly to antipyretics, which is often what brings the family to medical attention.
The rash, as the fever breaks. When the fever resolves, an erythematous, blanching macular or maculopapular rash appears — pink, non-pruritic, beginning on the trunk and neck and spreading to the face and limbs. It lasts hours to a couple of days and fades without desquamation or pigmentation. The rash appearing at defervescence (the fall of the fever), rather than during the fever, is the diagnostic feature.
Febrile seizures
The fever is also behind the illness’s main complication. About 10-15% of children with primary HHV-6B infection develop a febrile seizure, predominantly between 6 and 18 months of age. The mechanism is the immature brain’s response to a rapid rise in temperature rather than direct invasion of the central nervous system, and these are usually simple febrile seizures: generalised rather than focal, lasting a couple of minutes, and not followed by persistent neurological findings.
A well-appearing infant who has had a brief generalised seizure and whose fever has a recognisable source does not need a lumbar puncture or empirical antibiotics; the assessment follows the usual approach to febrile seizures. Where the child is unwell, drowsy, or has focal signs or a prolonged seizure, the usual concerns about meningitis and encephalitis take priority and the roseola pattern should not be assumed.
Diagnosis
The diagnosis is clinical. Fever followed by a rash at defervescence in an infant aged 6 months to 2 years is sufficient, and there is no role for serology, viral culture or swabs in the immunocompetent child.
Blood tests are usually not indicated, but when they are done incidentally they may show neutropenia, thrombocytopenia, raised transaminases or cholestasis (impaired bile flow). These reflect the viraemia and are not by themselves an indication for treatment or investigation.
Management
Management is supportive: antipyretics for comfort and fluids. There is no specific therapy for roseola in a healthy child, and none is needed — the disease is self-limited and the diagnostic step (the rash) arrives only after the illness has begun to resolve.
In immunocompromised patients the picture is different. HHV-6 reactivation after haematopoietic stem cell transplantation can cause encephalitis and other end-organ disease, and antiviral treatment such as ganciclovir or foscarnet is sometimes used in that setting. That is a different clinical problem from roseola in an infant, and it belongs with the management of the immunocompromised host.