“Systematic review of HHV-6 and febrile seizures: Should the ER include it in the viral panel?”

• HHV-6B remains an undertested cause of pediatric febrile seizures. • ciHHV-6 complicates diagnosis by mimicking active infection on PCR testing. • Neurologic complications of HHV-6 include seizures and postinfectious encephalitis. • Routine testing is impractical; selective testing may be cost-effective. • Future tools integrating PCR and serology could clarify true HHV-6 activity. Human herpesvirus 6 (HHV-6), particularly subtype B, is a common viral infection in childhood and the cause of roseola infantum. Beyond its dermatologic effects, HHV-6B is an important yet often underrecognized contributor to febrile seizures in young children presenting to the emergency department (ED). This systematic review aims to examine the virology, epidemiology, and clinical features of HHV-6 infection in children, focusing on neurologic manifestations, while evaluating current ED diagnostic practices and the potential role for HHV-6 testing in pediatric febrile seizures. Following PRISMA guidelines, a comprehensive search of PubMed and Embase databases identified studies published up to September 2025 on HHV-6 virology, dermatologic findings, neurologic complications, and ED management in pediatric patients. Inclusion criteria focused on HHV-6’s role in febrile seizures and the utility of rapid molecular diagnostics in the ED. Search terms included keywords related to HHV-6, febrile seizures, and pediatric emergency care. Two reviewers independently performed full-text reviews and extracted data. Primary HHV-6B infection affects most children by age two, with up to 30% of first febrile seizures in this group attributed to the virus. While mostly self-limited, HHV-6B is disproportionately associated with complex febrile seizures and febrile status epilepticus. Emerging rapid diagnostic tools offer opportunities for targeted testing in select high-risk populations but are costly. HHV-6B is an underrecognized cause of febrile seizures in pediatrics. Selective screening for complex or prolonged seizures may enhance improve long-term outcomes. Until stronger evidence emerges, clinicians should interpret HHV-6B results within the broader clinical context.