History
Human herpesvirus 6 (HHV-6) infection can be asymptomatic. Symptomatic manifestations occur predominately after primary infection in infants and after either primary or reactivation disease in immunocompromised adults.
HHV-6 is a common cause of hospital visits in infants with fever. Some estimates suggest that 20% of HHV-6 infections manifest as roseola, which is characterized by fever for 3-5 days and followed by an erythematous maculopapular rash. [8, 23] The rash starts at the trunk and spreads centrifugally to the face and limbs. More commonly, the infection presents as an acute nonspecific febrile illness in a child younger than 2 years. HHV-6 infection may also manifest as a rash alone.
Symptoms reported in children may include the following:
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Ear symptoms, otitis
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Upper respiratory tract symptoms
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Gastrointestinal (GI) symptoms, including liver dysfunction and hepatitis
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Fever-induced seizures [28]
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Bulging fontanelles
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Symptoms of meningoencephalitis [29]
Symptoms reported in adults may include the following:
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Fever with lymphadenopathy, a mononucleosislike syndrome
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Symptoms consistent with hepatitis
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Symptoms consistent with encephalitis (delirium, confusion, amnesia, ataxia, seizure)
Symptoms reported in immunocompromised hosts and transplant recipients may include the following:
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Fever, usually very high
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Symptoms of graft versus host disease (GVHD)
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Symptoms of graft rejection
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Symptoms of interstitial pneumonitis
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Symptoms of meningoencephalitis or myelitis [30]
Physical Examination
Physical findings of HHV-6 infection are those expected with the symptoms described (see History). Very few physical examination findings exist in children who are infected with HHV-6 until skin findings become apparent.
Findings in infants that may suggest HHV-6 infection include the following (see the images below):
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High-grade fever (>39.5°C [103°F]), typically persisting for 3-5 days and then resolving abruptly; undifferentiated febrile illness without rash or localizing signs is possible
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Erythematous macular or maculopapular rash on the trunk, arms, neck, and face, and later on the lower extremities; the rash commonly appears during or within a few hours after defervescence; it is nonpruritic and mildly elevated, consists of rose-pink papules, and blanches on pressure; it usually fades in 1-2 days
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Inflamed tympanic membranes
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Signs of upper and, occasionally, lower respiratory tract involvement
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Hepatomegaly (a common GI sign)
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Central nervous system (CNS) manifestations – Most children are playful despite high-grade fever; however, anorexia, irritability, and listlessness may be presenting signs; febrile seizures occur in 10%-15% of primary infections.
Nine-month-old infant boy presented with one-day history of high-grade fever and irritability. In the emergency department, the patient underwent septic workup, including lumbar puncture, with normal cerebrospinal fluid analysis results. He was admitted to the hospital. High-grade fever abruptly resolved on day 3 of hospitalization. Within a few hours, erythematous, pink papular (roseola) nonpruritic rash appeared, mainly on trunk.
N-month-old infant boy presented with one-day history of high-grade fever and irritability. In the emergency department, the patient underwent septic workup, including lumbar puncture, with normal cerebrospinal fluid analysis results. He was admitted to the hospital. High-grade fever abruptly resolved on day 3 of hospitalization. Within a few hours, erythematous, pink papular (roseola) nonpruritic rash appeared, mainly on trunk. Patient was playful after supportive therapy. Antibiotics were discontinued after 2 days of negative cultures.
HHV-6 infection in adults can have a wide variety of manifestations, which may range from mild to severe. Findings in healthy adults may include the following:
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Fever
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Lymphadenopathy
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Hepatosplenomegaly
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CNS manifestations (eg, meningismus and mental status changes)
Findings in immunocompromised individuals may include the following:
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Fever
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Rash
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Signs of pneumonitis
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Mental status changes
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Anterograde amnesia
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Hepatosplenomegaly
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Encephalitis
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Meningitis
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Seizure
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Myelosuppression
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Nine-month-old infant boy presented with one-day history of high-grade fever and irritability. In the emergency department, the patient underwent septic workup, including lumbar puncture (adhesive bandage), with normal cerebrospinal fluid analysis results. He was admitted to the hospital.
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Nine-month-old infant boy presented with one-day history of high-grade fever and irritability. In the emergency department, the patient underwent septic workup, including lumbar puncture, with normal cerebrospinal fluid analysis results. He was admitted to the hospital. High-grade fever abruptly resolved on day 3 of hospitalization. Within a few hours, erythematous, pink papular (roseola) nonpruritic rash appeared, mainly on trunk.
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N-month-old infant boy presented with one-day history of high-grade fever and irritability. In the emergency department, the patient underwent septic workup, including lumbar puncture, with normal cerebrospinal fluid analysis results. He was admitted to the hospital. High-grade fever abruptly resolved on day 3 of hospitalization. Within a few hours, erythematous, pink papular (roseola) nonpruritic rash appeared, mainly on trunk. Patient was playful after supportive therapy. Antibiotics were discontinued after 2 days of negative cultures.
