Roseola Infantum (Exanthem Subitum)

Roseola infantum, also known as exanthem subitum or sixth disease, is a ubiquitous, acute viral infection of infancy and early childhood. It is historically significant as the sixth of the traditional childhood exanthems. The condition is characterized by a distinctive clinical course: a period of high fever followed by the abrupt appearance of a rash just as the temperature normalizes.

Etiology and Epidemiology

The primary causative agent of roseola infantum is Human Herpesvirus 6 (HHV-6), specifically variant B (HHV-6B). A smaller percentage of cases are caused by the related Human Herpesvirus 7 (HHV-7). These viruses belong to the Roseolovirus genus of the Betaherpesvirinae subfamily.

• Age: The peak age of incidence is between 6 months and 3 years. It is a major cause of acute febrile illness in this age group, accounting for a significant proportion of emergency department visits for infants.
• Transmission: The virus is likely transmitted via the respiratory route or through saliva (oral secretions). Following the primary infection, the virus establishes latency and can be shed intermittently in the saliva of healthy adults, serving as a source of transmission to susceptible infants.

Clinical Manifestations

The clinical presentation of roseola is classically biphasic.

1. The Febrile Phase

The illness typically begins abruptly with a high fever, often ranging from 38.5°C to 40°C (101.3°F to 104°F).

• Duration: The fever usually persists for 3 to 4 days (range 3–7 days).
• General Condition: Despite the high temperature, the infant often appears remarkably well and alert ("non-toxic"), although some irritability and fussiness are common.
• Associated Symptoms: While high fever is the most consistent finding, other signs may include mild upper respiratory symptoms such as rhinorrhea, pharyngeal inflammation, and conjunctival redness. Mild cervical or occipital lymphadenopathy may be present. Palpebral edema (swelling of the eyelids) is another feature occasionally observed.
• Nagayama Spots: In some cases, ulcers known as Nagayama spots may be seen at the uvulopalatoglossal junction.

2. The Exanthematous Phase

The hallmark of roseola is the timing of the rash. The high fever resolves abruptly (by crisis) or gradually over 24 hours (by lysis). As the fever disappears (or within 12–24 hours of defervescence), the rash appears.

• Morphology: The rash consists of discrete, rose-colored or pink macules and papules (2–3 mm in diameter) that blanch on pressure.
• Distribution: It typically starts on the trunk and spreads centrifugally to the neck, face, and proximal extremities. This contrasts with measles and rubella, which typically start on the face and spread downward.
• Duration: The rash is non-pruritic and evanescent; it may last for 1 to 3 days or be visible for only a few hours before fading without desquamation or pigmentation.

Diagnosis and Differential Diagnosis

Diagnosis is primarily clinical, based on the characteristic history of high fever followed by a rash in an otherwise well-appearing infant. Laboratory investigations are rarely necessary but may show leukopenia with relative lymphocytosis.

Differential Diagnosis:

• Measles: Distinguished by the presence of significant cough, coryza, conjunctivitis, Koplik spots, and a rash that appears at the height of the fever, not after it subsides.
• Rubella: Characterized by significant retroauricular and suboccipital lymphadenopathy and a rash that appears coincident with low-grade fever.
• Drug Hypersensitivity: Because antibiotics are frequently prescribed for the initial high fever of roseola, the subsequent appearance of the rash is often misdiagnosed as an antibiotic allergy.
• Enteroviral Infections: Can cause fever and rash but do not typically follow the distinct "fever-then-rash" timeline.

Complications

While generally benign, roseola is a common cause of febrile seizures.

• Seizures: Convulsions occur in approximately 5–15% (up to one-third) of children during the febrile phase. HHV-6B is a frequently identified cause of febrile status epilepticus.
• CNS Involvement: Rarely, the virus can cause aseptic meningitis, meningoencephalitis, or encephalopathy.
• Immunocompromised Hosts: In patients with depressed cell-mediated immunity, primary or reactivated infection can cause severe disease, including pneumonia, marrow suppression, and encephalitis.

Management

There is no specific antiviral therapy recommended for routine cases of roseola infantum in immunocompetent children.

• Supportive Care: Management focuses on maintaining adequate hydration and using antipyretics (e.g., paracetamol) to control high fever and improve comfort.
• Antiviral Therapy: In rare, severe cases involving immunocompromised patients or severe encephalitis, agents such as ganciclovir, foscarnet, or cidofovir may be considered, although their efficacy is not definitively established by randomized trials.

Prognosis

The prognosis for roseola infantum is excellent. It is a self-limited illness with complete recovery in the vast majority of children. Even in children who experience febrile seizures associated with roseola, the risk of developing epilepsy or long-term neurologic sequelae is generally low and comparable to other causes of simple febrile seizures.