Roseola Infantum in Emergency Medicine

Roseola infantum is the sixth of the traditional exanthems of childhood. The condition is an acute benign disease of childhood classically characterized by a history of a prodromal febrile illness lasting approximately 3 days, followed by defervescence and the appearance of a faint pink maculopapular rash.

Since identification of the etiologic agent human herpesvirus type 6 (HHV-6), infection has been documented without the characteristic fever or rash. The virus may present as an acute 3-7 day febrile illness (characteristically >39.5 º C) associated with respiratory or gastrointestinal symptomatology. In one prospective cohort, 93% of newly acquired infections were symptomatic, with fever, fussiness, diarrhea, and rash as the most distinguishing features.[1]

Newly recognized clinical manifestations of HHV-6 infection include hepatitis, encephalitis, myocarditis, hemophagocytic syndrome, and an adult mononucleosislike illness. The virus persists and may reactivate, primarily in immunocompromised hosts. Reactivation manifestations may present as fever, rash, pneumonia, hepatitis, bone marrow suppression, and encephalitis.[2] The full spectrum of clinical manifestations of HHV-6 has not been elucidated.

Respiratory secretions of asymptomatic individuals likely transmit the virus. The child is most likely to spread the infection during the febrile and viremic phase of the illness.

Cell-associated viremia has been noted, usually on the third day of illness and immediately before rash appearance. By the eighth day of illness, antibody activity peaks and results in resolution of the viremia.

Children with the cell-free virus also have been noted. This likely represents a greater magnitude of viral dissemination because these children have more severe clinical manifestations.

Frequency

United States

Approximately 12-30% of children have clinical manifestations consistent with roseola. Eighty-six percent of children have acquired HHV-6 antibodies by age 1 year. By age 4 years, almost all children are seropositive. Roseola appears to peak in spring and fall.

International

A relationship seems to exist among prevalence, geographic location, and ethnicity. The prevalence of roseola is 92% in Ecuador, 60% in Japan, 20% in Morocco, and 49-76% in Malaysia. The disease is more prevalent among younger infants in Japan than in the United States or Europe.

Mortality/Morbidity

Roseola is usually a self-limited illness with no sequelae.

The major morbidity associated with roseola is seizures (6-15%) during the febrile phase of the illness.

Encephalitis, fulminant hepatitis, hemophagocytic syndrome, and disseminated infection with HHV-6 are extremely rare manifestations in healthy hosts. Immunosuppression secondary to transplantation may result in viral replication and reactivation. While HHV-6 is commonly detected post transplantation, it is generally asymptomatic. However, it has been implicated in encephalitis, hepatitis, bone marrow suppression, and pneumonitis in a minority of cases.[2]

Sex

No predilection for roseola infantum exists.

Age

Most cases present within the first 2 years of life, with peak occurrence in infants aged 9-21 months.

Symptoms of roseola infantum include the following:

• Roseola is typically characterized by a history of high fever followed by rapid defervescence and a characteristic rash.

• Fever (often up to 40°C and of 3-7 days' duration)

• Rash (fades within a few hours to 2 d)

  • Maculopapular or erythematous

  • Typically beginning on the trunk and may spread to involve the neck and extremities

  • Nonpruritic

  • Blanches on pressure

• Seizures (6-15%)

• Diarrhea (68%)

• Prodromal symptoms (14%)

  • Listlessness

  • Irritability

• Cough (50%)

Physical examination findings of roseola infantum include the following:

• Alert, nontoxic appearance

• Fever (98%)

• Rash (98%)

  • Rose pink macules or maculopapules approximately 2-5 mm in diameter are present.

    Discrete rose-pink macules/maculopapules characteristic of roseola infantum.

  • Lesions are characteristically discrete, rarely coalesce, and fade with blanching of the skin surface.

  • Typically, roseola infantum involves the trunk or back with minimal facial or proximal extremity involvement.

  • Some lesions may be surrounded by a halo of pale skin.

  • The rash typically evolves over 12 hours with a duration of 1-2 days.[3]

• Bulging anterior fontanel (26%)[4]

• Nagayama spots (erythematous papules on the soft palate and uvula) (65%)

• Periorbital edema, most common in the preexanthematous stage (30%); palpebral edema also common

• Cervical, postauricular, and postoccipital lymphadenopathy (31%)

• Splenomegaly

• Encephalopathy

• Conjunctival erythema

See the list below:

• HHV-6 was identified as the etiologic agent of roseola infantum in 1988.

  • This large, double-stranded deoxyribonucleic acid (DNA) virus is a member of the Herpesviridae family.

  • Two major strains, variants A and B, of this virus exist. HHV-6A appears to be more cytolytic and potentially more virulent. Strain B is responsible for most of the exanthem subitum infections in children.

  • The incubation period is approximately 9 days (range, 5-15 d).

  • Approximately 21% of primary infections will exhibit the classic clinical presentation of roseola infantum.[5]

• HHV-6B is not believed to be the only causative agent of exanthem subitum. Primary infection with human herpesvirus type 7 (HHV-7) has also been implicated in exanthem subitum, but it is typically asymptomatic.

• Transmission is usually horizontal via person-to-person oral secretions. Adult family members or older siblings appear to be the infective source. The virus has been found in the saliva of healthy adults. Although rare, vertical transmission has been reported with chromosomally integrated HHV-6 DNA.[6]

See the list below:

• Given the benign nature and short duration of roseola infantum, laboratory studies generally are not obtained if the child presents with a classic history.

• Diagnosis of primary HHV-6 can be confirmed by primary viral isolation from the peripheral blood.

• Specific immunoglobulin M (IgM) serology or a rise in HHV-6-specific immunoglobulin G (IgG) and HHV-6 DNA polymerase chain reaction can document infection, even distinguishing between HHV-6a and 6b.[7]

• If a complete blood count (CBC) is obtained, leukopenia may be noted. The white blood cell (WBC) count usually returns to reference ranges within a week.

Huang et al conducted a study to identify factors for differentiating roseola infantum from urinary tract infection (UTI) and to describe a cohort of infants diagnosed with roseola infantum and sterile pyuria. The study concluded that leukocytosis is the strongest predictor of UTI over roseola infantum. Sterile pyuria may occur in infants with roseola infantum.[8]

Treatment for roseola infantum is supportive.

To date, no controlled antiviral trials exist against HHV-6. However, treatment is recommended with end-organ disease in the transplantation population. Anecdotal reports of ganciclovir suggest that it may be beneficial in these patients.[9]

Because of the ubiquity of the virus, isolation of patients with HHV-6 infection is probably unnecessary.

Complications of roseola infantum may include the following:

• Febrile seizures

• Encephalitis (rare)[10]

• Meningitis

  • According to Yoshikawa and Asano, the presence of HHV-6 in cerebrospinal fluid has been demonstrated by polymerase chain reaction in 3 of 8 children with febrile seizures and in 3 of 3 children with encephalitis.[11]

  • CNS primary invasion and complications by HHV-6 appear to occur during the acute febrile portion of the illness.

• Hepatitis

• Latency - Like other herpes viruses, HHV-6 and HHV-7 may persist in the salivary glands, peripheral blood, and brain.[12] HHV-6 may reactivate following organ or marrow transplant and may mimic graft versus host disease. It additionally may have a possible role in the development of temporal lobe epilepsy in immunocompromised patients,[13] as well as the flare and severity of drug-induced hypersensitivity syndromes.[14]

See the list below:

• The clinical course of roseola infantum is acute and benign, and complete recovery without sequelae is expected.

• The skin eruption gradually fades and resolves without scarring.

For excellent patient education resources, visit eMedicine's Children's Health Center. Also, see eMedicine's patient education article Skin Rashes in Children.