Infant With High Fever and Rose-Pink Macular Rash at Defervescence

ANSWER: ROSEOLA INFANTUM 

Roseola infantum, also known as exanthem subitum or sixth disease, is a common childhood disease characterized by high fever that lasts 3 to 4 days followed by the sudden appearance of a rash at defervescence.^1,2

PREVALENCE

Infants and children between 6 months and 2 years of age are most frequently affected. Presumably, maternal antibodies protect most infants from infection during the first few months of life.³ By 12 and 18 months of age, approximately 65% and 95% of children, respectively, have become infected.³ Roseola infantum is rare after age 4 years.⁴ The sex ratio is equal. The condition occurs throughout the year.⁵

ETIOLOGY AND PATHOGENESIS

Human herpesvirus 6 (HHV-6) is the major cause of roseola infantum, the other cause being HHV-7.^4,6 Both are enveloped, double-stranded DNA viruses with an icosahedral capsid.⁷ They are members of the Roseolovirus genus of the Betaherpesvirinae subfamily.⁸

Transmission of the infection most likely results from asymptomatic shedding of the virus in the saliva of caregivers or other close contacts.⁵ The main route of transmission, by inoculation of the oropharynx, leads to replication of the virus in salivary glands.⁹ From the salivary glands, the virus gains access to T lymphocytes.⁹ The incubation period of HHV-6 is 5 to 15 days, while the incubation period of HHV-7 is not known.³ HHV-7 infection tends to occur later in life than HHV-6 and may account for second or recurrent cases of roseola infantum.⁶

CLINICAL MANIFESTATIONS

The prodromal period of roseola infantum is usually asymptomatic.⁵ The infected child generally has fever of abrupt onset, with temperatures in the range of 39°C (102°F) to 40.5°C (105°F). At defervescence, 3 to 4 days later, a rash suddenly appears—hence the term “exanthem subitum,” meaning sudden rash.^2,9 Most children are otherwise well and seem happy, alert, and playful.^1,6 However, some children may exhibit restlessness and irritability during times of increased fever.

The typical lesions of roseola infantum are rose-pink, macular, and of 2 to 3 mm in diameter (Figure). The eruption first appears on the trunk. It then spreads to the neck and proximal extremities, and occasionally the face.⁶ The rash usually blanches on pressure and subsides within 2 to 4 days.² Characteristically, lesions remain discrete but may become confluent, as in the patient described on page 387.⁵ Pruritus and desquamation are usually absent.⁹

Other potential findings include suboccipital, postauricular, and cervical lymphadenopathy; palpebral and periorbital edema (Berliner sign); tympanic membrane injection; erythematous maculopapular spots on the soft palate and vulva (Nagayama spots); and mild erythema of the pharynx.^1-3,6

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

The diagnosis is mainly clinical. The differential 

diagnosis includes, most importantly, drug allergy in a febrile child who is receiving antimicrobial therapy, along with other childhood exanthems:

• Drug allergy rash usually lasts longer than a few days and may be accompanied by pruritus and fever.
• Measles typically presents with cough, coryza, conjunctivitis, Koplik spots, and appearance of rash at the height of the fever.⁵
• Rubella generally causes low-grade fever, prominent occipital and postauricular lymphadenopathy, and an extensive rash.⁵
• Scarlet fever commonly manifests as sudden onset of sore throat, fever, a beefy red pharynx, enlarged and erythematous tonsils (with or without exudates), enlarged tender anterior cervical lymph nodes, and a rash. The rash typically blanches on pressure, has the texture of gooseflesh, or coarse sandpaper, and is better felt than seen. The rash may be more prominent in flexor skin creases, especially in the antecubital fossae (Pastia lines).

COMPLICATIONS

Febrile seizures occur in about 5% to 10% of children with roseola infantum.⁵ Rarely, meningitis, encephalopathy, thrombocytopenic purpura, hepatitis, inappropriate antidiuretic hormone secretion, and pneumonia may result from HHV-6 or HHV-7 infection.^1-3,7,9-11 Most children recover without sequelae.

MANAGEMENT

Roseola infantum is a benign, self-limited disease. There is no specific treatment. An antipyretic may be used to reduce fever and discomfort.

REFERENCES:
1. Leung AK. Roseola infantum. In: Lang F, ed. The Encyclopedia of Molecular Mechanisms of Disease. Berlin: Springer-Verlag; 2009:1868-1869.
2. Leung AK, Kao CP. A collage of infectious diseases in children. Consultant For Pediatricians. 2006;5:561-564.
3. Scott LA, Stone MS. Viral exanthems. Dermatol Online J. 2003;9(3):4.
4. Vianna RA, de Oliveira SA, Camacho LA, et al. Role of human herpesvirus 6 infection in young Brazilian children with rash illnesses. Pediatr Infect Dis J. 2008;27:533-537.
5. Leach CT. Roseola (human herpesviruses 6 and 7). In: Kliegman RM, Behrman RE, Jenson HB, et al. Nelson Textbook of Pediatrics. Philadelphia: Saunders Elsevier; 2007:1380-1383.
6. Dyer JA. Childhood viral exanthems. Pediatr Ann. 2007;36:21-29.
7. Caselli E, Di Luca D. Molecular biology and clinical associations of Roseoloviruses human herpesvirus 6 and human herpesvirus 7. New Microbiol. 2007;30:173-187.
8. Dockrell DH. Human herpesvirus 6: molecular biology and clinical features. J Med Microbiol. 2003;52:5-18.
9. Krafchik BR, Tellier R. Human herpesvirus 6 infection (roseola infantum). In: Harper J, Oranje A, Prose N, eds. Textbook of Pediatric Dermatology. 2nd ed. Oxford: Blackwell Publishing; 2006:410-411.
10. Shimura N, Kim H, Sugimoto H, et al. Syndrome of inappropriate secretion of antidiuretic hormone as a complication of human herpesvirus-6 infection. Pediatr Int. 2004;46:497-498.
11. Ward KN, Andrews NJ, Verity CM, et al. Human herpesviruses-6 and -7 each cause significant neurological morbidity in Britain and Ireland. Arch Dis Child. 2005;90:619-623.