Exanthem Subitum-Associated Encephalitis: Nationwide Survey in Japan

Yoshikawa, Tetsushi; Ohashi, Masahiro; Miyake, Fumi; Fujita, Ayano; Usui, Chie; Sugata, Ken; Suga, S.; Hashimoto, Shuji; Asano, Yoshizo

doi:10.1016/j.pediatrneurol.2009.05.012

Cited by 68 publications

(40 citation statements)

References 32 publications

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“…A nationwide survey in Japan showed an unexpectedly poor prognosis for exanthema subitum-associated encephalitis (157). In addition, two ultimately fatal cases of encephalopathy a HCMV, human cytomegalovirus; C or H, consistent or hypothetical association with HHV-6 (keeping in mind that robust large-scale studies are lacking in most cases, which makes this classification prone to frequent changes and subject to personal interpretation).…”

Section: Clinical Impacts Of Hhv-6 Infections Primary Infectionsmentioning

confidence: 99%

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

2015

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SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus.

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Section: Clinical Impacts Of Hhv-6 Infections Primary Infectionsmentioning

confidence: 99%

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

2015

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“…Surveys estimate that 60 cases of roseola per year are complicated by encephalitis in Japan, making it the second most common cause of infection-related encephalitis. Severe neurologic sequelae such as acute necrotizing encephalitis, hemorrhagic shock and acute encephalopathy with biphasic seizures complicate nearly half of those cases [38, 39]. Evidence suggests that this may be a cytokine-mediated disorder [40].…”

Section: Neurologic Complications and Sequelaementioning

confidence: 99%

Clinical impact of primary infection with roseoloviruses

Tesini

Epstein

Caserta

2014

Current Opinion in Virology

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The roseoloviruses, human herpesvirus-6A -6B and -7 (HHV-6A, HHV-6B and HHV-7) cause acute infection, establish latency, and in the case of HHV-6A and HHV-6B, whole virus can integrate into the host chromosome. Primary infection with HHV-6B occurs in nearly all children and was first linked to the clinical syndrome roseola infantum. However, roseolovirus infection results in a spectrum of clinical disease, ranging from asymptomatic infection to acute febrile illnesses with severe neurologic complications and accounts for a significant portion of healthcare utilization by young children. Recent advances have underscored the association of HHV-6B and HHV-7 primary infection with febrile status epilepticus as well as the role of reactivation of latent infection in encephalitis following cord blood stem cell transplantation.

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“…According to a recent survey, 3 an annual incidence of exanthem subitum-associated encephalitis/encephalopathy was estimated at 60 cases per year in Japan, and the prognosis of the disease was unexpectedly poor. In addition to primary infection, it has been suggested that HHV-6 reactivation can cause encephalitis in transplant recipients [4][5][6][7][8] and patients with drug-induced hypersensitivity syndrome.…”

Section: Introductionmentioning

confidence: 99%