Clinical Manifestations of primary infection with human herpesvirus 6 (HHV-6) include roseola (exanthem subitum) in approximately 20% of infected children, undifferentiated febrile illness without rash or localizing signs, and other acute febrile illnesses (febrile seizures, encephalitis and other neurologic disorders, and mononucleosis-like syndromes), often accompanied by cervical and postoccipital lymphadenopathy, gastrointestinal tract or respiratory tract signs, and inflamed tympanic membranes. Fever characteristically is high (temperature greater than 39.5°C [103.0°F]) and persists for 3 to 7 days. Approximately 20% of all emergency department visits for febrile children 6 through 12 months of age are attributable to HHV-6. In roseola, an erythematous maculopapular rash lasting hours to days is noted once fever resolves. Febrile seizures occur during the febrile period in approximately 10% to 15% of primary infections. A bulging anterior fontanelle occurs occasionally in patients with roseola. HHV6 and HHV7 may cause neurologic disease, including encephalitis. The virus persists and may reactivate. The clinical circumstances and manifestations of reactivation in healthy people are not known. Illness associated with reactivation, primarily in immunocompromised hosts, has been described in association with manifestations such as fever, rash, hepatitis, bone marrow suppression, pneumonia, and encephalitis.

Recognition of the varied Clinical Manifestations of human herpesvirus 7 (HHV-7) infection is evolving. Many, if not most, primary infections with HHV-7 may be asymptomatic or mild; some may present as typical roseola and may account for second or recurrent cases of roseola. Febrile illnesses associated with seizures also have been reported. Some investigators suggest that the association of HHV-7 with these Clinical Manifestations results from the ability of HHV-7 to reactivate HHV-6 from latency.