Roseola Infantum (exanthum subitum, sixth disease)

Are You Confident of the Diagnosis?

What you should be alert for in the history

Roseola infamtum is a common infectious disease of infancy characterized by a rash proceeded for 3-5 days by high fever (40-40.5°C; 104-105°F) in an otherwise healthy appearing infant.

Characteristic findings on physical examination

These include rose pink macules and papules on the trunk, neck, extremities, and less commonly on the face. Upper respiratory findings such as injection of the tympanic membranes, in addition to cervical or occipital lymphadenopathy may be appreciated. Red papules on the soft palate may be seen (Nagayama’s spots), as well as uvulo-palatoglossal junction ulcers. Bulging fontanelles, seizures, encephalopathy, or aseptic meningitis may alert the practitioner to neurological involvement

Expected results of diagnostic studies

Laboratory investigations for diagnosing human herpesvirus (HHV) include serologies, antigen detection, PCR, and immunofluorescence.

Diagnosis confirmation

Differential diagnoses include other viral exanthems such as adenovirus, enterovirus, parvovirus B19, rubella, and parainfluenza.

Who is at Risk for Developing this Disease?

Infants and toddlers between 6 months and 3 years of age are the highest risk group with the peak age being 6-7 months. It is more common in the spring.

What is the Cause of the Disease?

HHV-6 and HHV-7. HHV-6 and HHV-7 is acquired via respiratory droplet. The virus replicates in T cells, although widespread infection is possible. Viremia occurs 2 days prior to the onset of fever, and is self-limiting. Latency is established and most commonly occurs in the salivary glands and peripheral blood mononuclear cells.

Systemic Implications and Complications

Patients with HIV or immunosuppressed patients may experience reactivation of the virus. The non-specific features of fever, malaise, and rash may mimic acute graft-versus-host disease. Bone marrow failure, neurological involvement, or pneumonitis may ensue. Since HHV-6 has several genes which transactivate long terminal repeat (LTR) of HIV, it is proposed that HHV-6 may have a role as the cofactor for AIDS.

Treatment Options

In most cases the disease is mild and self-limiting, and treatment is supportive using antipyretics, such as acetaminophen during the febrile stage. In more severe cases, ganciclovir or foscarnet have activity against HHV-6 and HHV-7. The virus is less responsive to acyclovir.

Optimal Therapeutic Approach for this Disease

Use anti-virals as above in severe disease, and control fever with anti-pyretics as needed.

Patient Management

The otherwise healthy infant can be managed as an outpatient. At the onset of the rash, the fever should improve, with the rash resolving in 5-10 days.

In a patient with neurological symptoms, inpatient monitoring is necessary, and initiation of anti-virals should be strongly considered.

Unusual Clinical Scenarios to Consider in Patient Management

Intractable seizures following roseola have been reported.

HHV-6 has been implicated as an etiologic agent in drug hypersensitivity syndomes, with ganciclovir being used therapeutically

What is the Evidence?

Torigoe, S, Kumamoto, T, Koide, W, Taya, K, Yamanishi, K. “Clinical manifestations associated with human herpesvirus 7 infection”. Arch Dis Child. vol. 72. 1995 June. pp. 518-519. (Documents association of herpes virus with clinical manifestations of roseola.)

Dyer, JA. “Childhood Viral Exanthems”. Pediatr Ann. vol. 36. 2007 Jan. pp. 21-9. (Provides clincal overview of childhood exanthems including roseola.)