Human herpesvirus 6 and drug allergy

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Abstract
The similarity between viral skin eruption and drug-induced rash has inspired many researchers to seek an association between viral infection and drug allergy. Hypersensitivity syndrome (referred to in this review as drug-induced hypersensitivity syndrome) is one of the severe adverse reactions to drugs and was reported more than 50 years ago. However, the mechanism of drug-induced hypersensitivity syndrome has not been fully elucidated. Several groups reported the association between human herpesvirus 6 reactivation and drug-induced hypersensitivity syndrome 5 years ago. Recently, similar case reports have accumulated. Recent findings concerning human herpesvirus 6 and drug-induced hypersensitivity syndrome are reviewed here. In drug-induced hypersensitivity syndrome, examination of serial serum samples revealed a marked and sudden increase in anti-human herpesvirus 6 IgG titers in the third or fourth week after the onset of clinical manifestations. In addition, active human herpesvirus 6 replication precedes the rise in antibody titers. Furthermore, the recurrence or worsening of signs and symptoms was observed concurrently with human herpesvirus 6 reactivation. In encephalitis associated with drug-induced hypersensitivity syndrome, human herpesvirus 6 DNA was detected in cerebrospinal fluid. This strongly indicates the involvement of reactivated human herpesvirus 6 in the pathogenesis of encephalitis. Similarly, reactivation of human herpesvirus 6 was observed in fulminant type 1 diabetes mellitus associated with drug-induced hypersensitivity syndrome caused by carbamazepine. The reactivation of human herpesvirus 6 in drug-induced hypersensitivity syndrome is not a coincidental phenomenon. Human herpesvirus 6 reactivation plays an important role in the pathogenesis of drug-induced hypersensitivity syndrome, especially in the latter half of the clinical symptoms. Reactivated human herpesvirus 6 sometimes leads to the severe complications of drug-induced hypersensitivity syndrome, such as encephalitis and type 1 diabetes mellitus. In conclusion, drug-induced hypersensitivity syndrome is a complex disease composed of drug allergy and human herpesvirus 6.