Human herpesvirus 6 infection in children: Clinical manifestations, diagnosis, and treatment

INTRODUCTION — The clinical manifestations, diagnosis, and treatment of human herpesvirus 6 (HHV-6) infection in children will be discussed here. Roseola and the virology, pathogenesis, and epidemiology of HHV-6, the clinical manifestations, diagnosis, and treatment of HHV-6 infections in adults, and HHV-6 infection in hematopoietic cell transplant recipients are discussed separately.

●(See "Roseola infantum (exanthem subitum)".)

●(See "Virology, pathogenesis, and epidemiology of human herpesvirus 6 infection".)

●(See "Clinical manifestations, diagnosis, and treatment of human herpesvirus 6 infection in adults".)

●(See "Human herpesvirus 6 infection in hematopoietic cell transplant recipients".)

VIROLOGY — HHV-6 is a member of the Herpesviridae family. HHV-6 replicates in activated CD4+ T lymphocytes [1]. There are two HHV-6 species: HHV-6A and HHV-6B. HHV-6B causes the majority of documented primary infections and reactivations events. Little is known about the epidemiology or clinical implications of HHV-6A. (See "Virology, pathogenesis, and epidemiology of human herpesvirus 6 infection", section on 'Virology and pathogenesis'.)

Like other herpesviruses, HHV-6 establishes latency after primary infection and may reactivate in immunocompromised hosts, especially after allogeneic hematopoietic cell transplantation. (See "Human herpesvirus 6 infection in hematopoietic cell transplant recipients".)

Latency of HHV-6 usually occurs through integration into the telomeric region of a human chromosome as a result of homologous recombination, typically in a small proportion of somatic cells [2]. However, integration into germline cells is responsible for congenital HHV-6 infections [3].

EPIDEMIOLOGY AND TRANSMISSION — HHV-6 infects most children within the first two years of life [4,5], but rarely may be acquired in adulthood [6]. In developed countries, the rate of seroprevalence among adults is generally >70 percent. (See "Virology, pathogenesis, and epidemiology of human herpesvirus 6 infection", section on 'Epidemiology'.)

Although there are few data regarding the incubation period of HHV-6 infection, it is thought to be approximately nine days (range 5 to 15 days) [7,8].

Transmission may occur:

●Prenatally – Prenatal transmission generally occurs through germline transmission of chromosomally integrated HHV-6 from either parent [3,9]. In utero transmission of reactivated virus or primary infection (ie, initial infection or infection with a new strain) occurs rarely. (See 'Congenital infection' below.)

●Postnatally – Postnatal transmission occurs mainly through saliva. Transmission through breast milk or blood products has not been reported [10]. Transmission through organ or hematopoietic cell donation has been reported rarely [11-14].

In approximately 1 percent of people, HHV-6 DNA is integrated into chromosomes, including chromosomes in germline cells [15]. Children born to individuals with chromosomally integrated HHV-6 can have one copy of virus per nucleated cell [16-18]. When an individual with chromosomally integrated HHV-6 donates hematopoietic stem cells, the transplant recipient will have integrated virus in their nucleated hematopoietic cells.

CLINICAL MANIFESTATIONS — The clinical manifestations of HHV-6 infection vary with the age and immune competence of the child.

Congenital infection — Congenital HHV-6 infection occurs in approximately 1 percent of newborn infants [3,19,20]. Most congenital infections with HHV-6 are asymptomatic. However, subtle neurodevelopmental effects may occur [21]. Although congenital HHV-6 has been associated with more severe manifestations (eg, respiratory failure, cardiac and gastrointestinal anomalies), the causal role of HHV-6 could not be determined [22].

Immunocompetent children — The classic manifestations of primary HHV-6 infection in immunocompetent children are roseola infantum (also known as exanthem subitum and sixth disease) and acute febrile illnesses with or without a rash. Other nonspecific symptoms, such as fussiness and rhinorrhea, can occur with primary infection in the absence of fever [4]. Other clinical syndromes (eg, hepatitis, myocarditis, encephalitis) may occur, sometimes in the setting of coinfection with another viral illness [23,24].

Acute febrile illness — Primary HHV-6 infection often presents as a febrile illness without a rash [4,5,25-28]. In a prospective study of 81 children with well-defined onset of primary HHV-6 infection, fever (57 percent), fussiness (69 percent), and rhinorrhea (65 percent) were the most frequent manifestations [4]. Cough, diarrhea, and rash occurred in a minority of children. In another prospective study of 160 children who presented to the emergency department for acute febrile illness and were found to have primary HHV-6 infection, the mean temperature at the time of presentation was 39.6°C (103.3°F), compared with 38.9°C (102.0°F) in children without HHV-6 [5]. Fever was most commonly accompanied by irritability, otitis media, upper and lower respiratory symptoms, or diarrhea. Seizures occurred in 13 percent.

●Febrile seizures – HHV-6 infection has been associated with febrile seizures [5,29-31]. (See "Clinical features and evaluation of febrile seizures", section on 'Infection'.)

Roseola infantum — HHV-6 is the most frequent cause of roseola infantum (exanthem subitum, also called roseola or sixth disease). Roseola is characterized by three to five days of high fever that resolves abruptly and is followed by development of a rash (picture 1). Approximately 25 to 30 percent of children with primary HHV-6 infection develop roseola [4,32]. (See "Roseola infantum (exanthem subitum)".)

Less common manifestations

●Meningoencephalitis – Encephalitis of variable severity can rarely occur as a complication of roseola or as the primary manifestation of HHV-6 infection in otherwise immunocompetent hosts [33-38]. Panencephalitis is most common, but a focal necrotic encephalitis mimicking herpes simplex virus encephalitis has been reported [33,39]. The detection of viral antigens in neural cells suggests that the encephalitis is caused by a direct viral effect, but immune-mediators also may play a role [40]. (See "Acute viral encephalitis in children: Clinical manifestations and diagnosis", section on 'Clinical features'.)

●Mesial temporal lobe epilepsy – HHV-6 has been associated with mesial temporal lobe epilepsy (MTLE). In pathology studies, HHV-6 DNA was recovered more frequently from brain biopsies from patients with MTLE than from patients without MTLE, suggesting that HHV-6 has pathologic effects [41-43]. (See "Focal epilepsy: Causes and clinical features", section on 'Mesial temporal lobe epilepsy'.)

●Mononucleosis-like syndrome – HHV-6 has also been reported in association with a mononucleosis-like syndrome in infants and adults [6,44-46]. (See "Clinical manifestations, diagnosis, and treatment of human herpesvirus 6 infection in adults", section on 'Primary infection'.)

●Hepatitis – HHV-6 has also been reported in association with liver failure of unknown etiology [47,48].

Unproven associations — HHV-6 may be activated by a number of acute illnesses. In many of these clinical syndromes, it is difficult to establish HHV-6 as the causative agent. Associations between HHV-6 and the following conditions have been proposed but remain unproven:

●Pneumonitis [49]

●Myocarditis, cardiomyopathy, and congenital heart disease [50-54]

●Immune thrombocytopenia [55,56]

●Viral associated hemophagocytic syndrome [57-59]

●Langerhans cell histiocytosis [60]

●Papular-purpuric "gloves and socks" syndrome [61]

●Gianotti-Crosti syndrome [62]

●Purpura fulminans [63]

●Guillain-Barré syndrome [64]

●Facial nerve palsy [65,66]

●Drug reaction with eosinophilia and systemic symptoms, also known as drug-induced hypersensitivity syndrome (see "Drug reaction with eosinophilia and systemic symptoms (DRESS)", section on 'Reactivation of Herpesviridae')

●Encephalopathy, hepatitis [67]

Immunocompromised children — Children with primary or secondary cellular immune deficiencies are more likely than immunocompetent children to have clinically relevant reactivation or new infection with herpesviruses such as HHV-6. However, establishing HHV-6 as the cause in such children is problematic for several reasons, including:

●Children with cellular immune deficiencies are frequently coinfected with other herpesviruses, such as cytomegalovirus (CMV), and other opportunistic infections [68]. Rises in antibody titers often occur against several viruses simultaneously.

●The high prevalence of viral DNA in peripheral blood mononuclear cells of healthy controls limits the use of qualitative polymerase chain reaction (PCR) to discriminate between latency and active infection.

Examples of clinical manifestations HHV-6 infection in immunocompromised children include:

●Children with cancer – In children with lymphoma, HHV-6 has been associated with decreased white blood cell count and hemoglobin. In an observational study, herpesvirus DNA (HHV-6 or CMV) was detected by PCR in the plasma or white blood cells of children with Hodgkin or non-Hodgkin lymphoma more often than in controls (46 versus 10 percent) [69]. Detection of both HHV-6 and CMV was associated with more frequent episodes of febrile neutropenia, absolute neutrophil count <800 cells/microL, lymphocytes <500 cells/microL, and hemoglobin <9.1 g/dL. Detection of HHV-6 DNA was predictive of immunosuppression before the onset of CMV infection.

In a cross-sectional study of beta-herpesviruses (HHV-6, HHV-7, and CMV) in 30 children with cancer, HHV-6B DNA was detected in the blood of four patients (13 percent) [70]. HHV-6B DNA was associated with hepatitis in one case and mild viral illness in another. Although HHV-6B was detected less frequently in children with cancer than in a control group of children with solid organ transplants, it should be considered in the differential diagnosis of febrile children with cancer.

●Transplant recipients – HHV-6 reactivation syndromes occur in approximately 50 percent of hematopoietic cell transplant (HCT) recipients and 20 to 62 percent of solid organ transplant recipients [71,72]. Primary HHV-6 infection has also been reported among solid organ transplant recipients [73-75]. Clinical manifestations of HHV-6 in HCT recipients are discussed in detail separately. HHV-6 encephalitis is the most clearly established clinical manifestation of HHV-6 reactivation in allogenic HCT recipients and is the most common cause of encephalitis in this population. Early recognition and empiric therapy are crucial. (See "Human herpesvirus 6 infection in hematopoietic cell transplant recipients", section on 'HHV-6 encephalitis'.)

Reactivation of HHV-6 usually occurs two to four weeks posttransplantation [76]. Rarely, primary infection with HHV-6 can occur through transmission from the donor [11-13,75]. In addition, HHV-6 may be a cofactor for CMV disease in transplant recipients [72,77].

HHV-6 infection has been reported in adult and pediatric transplant recipients. The majority of HHV-6 infections in transplant recipients are asymptomatic [71]. However, the following manifestations have been described in children who have undergone HCT or solid organ transplantation:

•Unexplained fever [71,78,79]

•Viremia [76]

•Rash [13,80]

•Hepatitis [12,71]

•Pneumonitis [71,81,82]

•Myocarditis [83]

•Encephalitis [71,84-87]

•Colitis [88]

•Bone marrow suppression [71,89,90]

•Macrophage activation syndrome [91]

•Graft failure [84]

•Graft rejection [71]

•Graft-versus-host disease (GVHD) in some [81,92], but not all reports [76,93]

Early reactivation of HHV-6 with high levels of HHV-6 DNAemia (ie, >1000 HHV-6 DNA copies/mL) is associated with increased reactivation of CMV (which may worsen posttransplant pneumonitis), increased rates of grades II to IV acute GVHD, and increased nonrelapse mortality [77,94,95]. (See "Human herpesvirus 6 infection in hematopoietic cell transplant recipients", section on 'Disease associations'.)

DIAGNOSIS

In immunocompetent children — In immunocompetent children with typical presentations of HHV-6 (eg, acute illness with high fever, with or without rash, and nonspecific symptoms), laboratory confirmation of HHV-6 is seldom necessary and is unlikely to affect management. In these children, HHV-6 generally resolves spontaneously without adverse effects.

A clinical diagnosis of roseola can be made in young children with the classic presentation (eg, fever for three to five days followed by abrupt defervescence and development of a rash (picture 1)). (See "Roseola infantum (exanthem subitum)", section on 'Clinical features'.)

Indications for laboratory confirmation — Laboratory confirmation of HHV-6 may be necessary in immunocompromised children or immunocompetent children with atypical presentations or complications (eg, meningoencephalitis). In such patients, diagnosis of HHV-6 may affect management (eg, antimicrobial therapy, immunosuppressive therapy) or facilitate monitoring of the clinical course and/or therapy [1]. (See 'Treatment' below.)

The diagnosis of HHV-6 encephalitis in hematopoietic cell transplant recipients is discussed separately. (See "Human herpesvirus 6 infection in hematopoietic cell transplant recipients", section on 'Diagnosis'.)

Approach to laboratory testing — Confirmation of HHV-6 as a causative pathogen is complicated by the high seroprevalence of HHV-6 in individuals older than three years, the persistence of HHV-6 DNA after primary infection (figure 1) [5], and the possibility of integration of HHV-6 DNA into chromosomes (in approximately 1 percent of the population). In addition, reactivation of HHV-6 may occur in healthy children without apparent illness [96]. Available microbiologic methods can establish the presence of replicating HHV-6, but not causality or the timing of infection (eg, acute versus reactivation, versus reinfection) (table 1).

Confirmation that an illness is caused by HHV-6 typically requires a compatible clinical syndrome, evidence of active HHV-6 infection (ie, with viral replication), and elimination of other conditions in the differential diagnosis [97,98]. A combination of laboratory tests may be necessary [99]. Consultation with an expert in infectious diseases is suggested. (See 'Exclusion of other conditions' below.)

Compatible clinical features — Clinical features that are compatible with active HHV-6 infection include [1]:

●A predisposing condition (eg, defect in cellular immunity)

●Dynamics of viral replication or serologic response (if obtained) that follow the clinical course

●Clinical findings that correspond to HHV-6 tropism, particularly in immunocompetent children (eg, viremia, encephalitis)

●No evidence of other pathogens known to cause the clinical syndrome (eg, herpes simplex virus in children with encephalitis) (see 'Exclusion of other conditions' below)

Compatible clinical features help to differentiate HHV-6 infection from incidental detection of HHV-6 (eg, latent infection or asymptomatic reactivation) given the high seroprevalence of HHV-6 in individuals >3 years of age and the persistence of HHV-6 after primary infection (figure 1) [5].

Compatible clinical features also help differentiate HHV-6 infection from HHV-6 detection due to integration of HHV-6 DNA into chromosomes (in approximately 1 percent of the population).

Evidence of HHV-6 infection with viral replication — A variety of tests can be used to provide evidence of HHV-6 infection and replication (table 1), and may help to determine the timing of infection. A combination of laboratory tests may be necessary [99]. Viral replication indicates active infection (primary infection or reactivation) [1,100]. Viral replication in patients with negative serology suggests primary infection rather than reactivation.

●Quantitative real-time HHV-6 PCR – Among the available tests, quantitative real-time HHV-6 polymerase chain reaction (PCR) provides the most useful information (table 1). Quantitative real-time HHV-6 PCR may be performed on any tissue; it is typically performed on whole blood, serum, plasma, and cerebrospinal fluid (CSF). It is highly sensitive and specific and permits HHV-6 speciation. High HHV-6 viral load in the CSF supports HHV-6 as the causative pathogen, particularly in an immunocompromised child [101].

Quantitative PCR of whole blood, as well as plasma, serum and peripheral mononuclear cells, may facilitate preliminary categorization of infection according to levels of HHV-6 DNA [1,102-106]:

•Latent: Low levels

•Active: Intermediate levels

•Chromosomally integrated HHV-6: High levels (typically >1 million copies/mL)

These categorizations are only preliminary because quantitative thresholds for "low," "intermediate," and "high," and a specific threshold for active versus chromosomally integrated HHV-6 infection, have not been established [1].

●Reverse transcriptase and droplet digital PCR – For patients with intermediate or high levels of HHV-6 DNA, additional PCR techniques may be helpful in distinguishing latent from active infection or diagnosing chromosomally integrated HHV-6 DNA:

•Reverse transcriptase PCR – In research laboratories, for patients with intermediate or high levels of HHV-6 DNA, positive reverse transcriptase PCR (RT-PCR), which detects HHV6-mRNA, indicates active infection (table 1) [99,100].

RT-PCR can be performed on blood and plasma. In addition, a multiplex RT-PCR microarray including seven neurotropic viruses (eg, HHV-6, herpesviruses, human enteroviruses) is commercially available for central nervous system viral infection detection in CSF [107].

•Droplet digital PCR – Droplet digital PCR, which provides precise quantitation of the ratio of HHV-6 to cellular DNA, can be used to identify chromosomally integrated HHV-6 [108].

●Qualitative HHV-6 PCR – Qualitative real-time HHV-6 PCR may be performed on any tissue; it is typically performed on whole blood, serum, plasma, and CSF. It is sensitive and specific and permits HHV-6 speciation. However, it does not differentiate between latent infection, active infection, and chromosomally integrated DNA [1,46,97,109-112].

The availability of multiplex PCR-based tests has enhanced identification of causative agents for meningitis and encephalitis. However, detection of HHV-6 with multiplex PCR-based tests is not sufficient evidence of causation. In an immunocompetent child, particularly if there is credible evidence of an alternate diagnosis for the neurologic findings, detection of HHV-6 more commonly represents viral latency, asymptomatic reactivation, or chromosomal integration than HHV-6 meningitis or encephalitis (given that HHV-6 infections are common and occur early in life) [97,113]. (See 'Exclusion of other conditions' below.)

●Viral culture – Viral culture may be performed on peripheral blood mononuclear cells, CSF, and a variety of tissues. A positive viral culture indicates replication and permits HHV-6 speciation.

Viral culture is not always available and is limited by its low sensitivity, technical difficulty, and long turn-around time [1].

●Antigen detection – Monoclonal antibodies against specific HHV-6A and HHV-6B antigens, as well as a polyclonal antibody against HHV-6 U90 protein, indicate viral replication and permit HHV-6 detection and speciation in blood and tissue [114-116]. However, antigen detection is not standardized and has limited sensitivity [1].

●Serology – Serologic tests for the detection of HHV-6 IgG antibody include indirect immunofluorescence assays, anticomplement immunofluorescence, competitive radioimmunoassay, and neutralization and enzyme immunoassays [117-119]. The sensitivity of these assays varies. Serologic assays do not distinguish between the HHV-6A and HHV-6B variants and cross-react with other beta-herpesviruses (eg, HHV-7 and cytomegalovirus [CMV]).

Because most people ≥2 years of age are seropositive for HHV-6 (figure 1), a single positive result cannot be interpreted. Paired sera need to be collected, with a ≥4-fold rise in titers considered diagnostic [120]. Seroconversion from negative to positive is good evidence of primary infection.

HHV-6 immunoglobulin M (IgM) develops within four to seven days of infection. However, many culture-positive children do not develop detectable IgM responses, and approximately 5 percent of healthy adults are IgM positive at any given time, making this test unreliable for a definitive diagnosis of active disease [121]. The mu-capture immunoassay appears to perform more accurately than older generation assays and does not cross react with Epstein-Barr virus or CMV IgM-positive sera [122].

Exclusion of other conditions — The differential diagnosis of HHV-6 infection depends upon the clinical presentation and immunocompetence of the host:

●Acute febrile illness – The differential diagnosis of acute febrile illness with nonspecific symptoms in an immunocompetent child includes other common childhood illnesses. Given that the illness usually resolves spontaneously within a few days, it generally is not necessary to identify the specific pathogen. The evaluation of fever in young children is discussed separately. (See "Fever without a source in children 3 to 36 months of age: Evaluation and management".)

●Fever and rash (roseola) – The differential diagnosis of roseola includes other infectious exanthems and drug allergy (figure 2). (See "Roseola infantum (exanthem subitum)", section on 'Differential diagnosis'.)

●Febrile seizure – The differential diagnosis of febrile seizure includes nonepileptic events or movements, provoked seizures from central nervous system infection (eg, meningitis or encephalitis), and rare forms of genetic epilepsy in which seizures are particularly common with fever. (See "Clinical features and evaluation of febrile seizures", section on 'Differential diagnosis'.)

●Meningoencephalitis – The differential diagnosis of meningoencephalitis in immunocompetent children includes other central nervous system infections, postinfectious encephalitis, autoimmune encephalitis, toxic metabolic conditions, and noninfectious intracranial pathology. (See "Acute viral encephalitis in children: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)

TREATMENT

Indications — In immunocompetent children, HHV-6 infection usually is a benign disease that resolves spontaneously and does not require specific therapy.

Antiviral therapy may be warranted for HHV-6 infections associated with increased morbidity (eg, encephalitis, myocarditis) in both immunocompetent and immunocompromised hosts, although efficacy data are limited and no controlled trials have been reported. If feasible, discontinuation or decreased doses of immunosuppressive therapy also may be warranted [1]. Given the lack of high-quality evidence for treatment of HHV-6 infection, consultation with an expert in pediatric infectious diseases is suggested.

Supportive care and long-term follow-up for children with encephalitis and treatment of HHV-6 encephalitis in hematopoietic cell recipients are discussed separately. (See "Acute viral encephalitis in children: Treatment and prevention" and "Human herpesvirus 6 infection in hematopoietic cell transplant recipients", section on 'Antiviral selection'.)

Choice of therapy — When treatment of HHV-6 infection is necessary, ganciclovir or foscarnet generally is preferred to cidofovir [1], because cidofovir is nephrotoxic [123]. (See "Foscarnet: An overview" and "Ganciclovir and valganciclovir: An overview" and "Cidofovir: An overview".)

Controlled trials of antiviral therapy for HHV-6 infection are lacking. In vitro, HHV-6 is susceptible to foscarnet, ganciclovir, and cidofovir [124]. Foscarnet and cidofovir are active against both HHV-6A and HHV-6B [124]. Ganciclovir is active against HHV-6B, but in some reports HHV-6A was relatively resistant [125-127].

Several case reports and case series have suggested improvement in presumed HHV-6 encephalitis after administration foscarnet or ganciclovir [128-132]. However, in a small case series of HHV-6 encephalitis in immunocompetent children, neurologic symptoms did not improve with ganciclovir therapy [35]. In another retrospective study, ganciclovir prophylaxis in children receiving hematopoietic cell transplant was associated with a decrease in HHV-6 reactivation and HHV-6 viral load [133]. These findings require confirmation in controlled trials.

Response to therapy — Response to therapy is determined by improvement in clinical symptoms and decreased viral load (if viral load was measured at diagnosis) [1].

Clinical improvement without decrease in viral load or decrease in viral load without clinical improvement may indicate that HHV-6 was not the causative agent. Lack of improvement may indicate the emergence of resistance and susceptibility testing may be warranted [134,135].

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SUMMARY AND RECOMMENDATIONS

●Epidemiology – Human herpesvirus 6 (HHV-6) infects most children within the first two years of life. In developed countries, the rate of seroprevalence among adults is >70 percent. Transmission occurs mainly through saliva. (See 'Epidemiology and transmission' above.)

●Clinical presentation

•The clinical presentations of HHV-6 infection vary with the age and immune-competence of the child.

•The incubation period ranges from 5 to 15 days. (See 'Clinical manifestations' above.)

•The classic manifestations of primary HHV-6 infection in immunocompetent children are acute febrile illnesses with or without a rash and roseola infantum (picture 1) (also known as exanthem subitum and sixth disease). (See 'Acute febrile illness' above and "Roseola infantum (exanthem subitum)".)

●Associated syndromes

•HHV-6 has been reported in association with a variety of other clinical syndromes (eg, hepatitis, myocarditis). However, HHV-6 may be activated by a number of acute illnesses, and it is difficult to establish HHV-6 as the causative agent. (See 'Less common manifestations' above and 'Unproven associations' above.)

•Reactivation of HHV-6 may be associated with clinically relevant clinical syndromes (eg, encephalitis, pneumonitis) in immunocompromised children, including hematopoietic cell or solid organ transplant recipients. (See 'Immunocompromised children' above.)

●Diagnosis

•In immunocompetent children with typical presentations of HHV-6 (eg, acute illness with high fever, with or without rash, and nonspecific symptoms), laboratory confirmation of HHV-6 is seldom necessary and is unlikely to affect management. (See 'In immunocompetent children' above.)

•Laboratory identification of HHV-6 may be necessary in immunocompromised children or immunocompetent children with atypical presentations or complications (eg, meningoencephalitis). (See 'Indications for laboratory confirmation' above.)

•Confirmation that an illness is caused by HHV-6 typically requires a compatible clinical syndrome, evidence of active HHV-6 infection (ie, with viral replication), and elimination of other conditions in the differential diagnosis. A combination of laboratory tests may be necessary (table 1). (See 'Approach to laboratory testing' above.)

●Differential diagnosis – The differential diagnosis of HHV-6 infection includes other causes or mimics of acute febrile illness, fever and rash (figure 2), febrile seizures, and meningoencephalitis. (See "Fever without a source in children 3 to 36 months of age: Evaluation and management" and "Roseola infantum (exanthem subitum)" and "Clinical features and evaluation of febrile seizures" and "Acute viral encephalitis in children: Clinical manifestations and diagnosis".)

●Treatment – HHV-6 infection is usually self-limited and does not warrant specific therapy. Antiviral therapy may be warranted for HHV-6 infections associated with increased morbidity (eg, encephalitis, myocarditis) in both immunocompetent and immunocompromised hosts; consultation with an expert in pediatric infectious diseases is suggested. (See 'Treatment' above.)