title: Human herpesvirus 6 and drug allergy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Ehime University School of Medicine, Ehime, Japan. hashik@m.ehime-u.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Masataka
authors.initials: M
authors.lastname: Yasukawa
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tohyama
mesh_terms: D015703:Antigens, CD; D003920:Diabetes Mellitus / Q000276:immunology / Q000821:virology; D004342:Drug Hypersensitivity / Q000150:complications / Q000276:immunology / Q000821:virology*; D018792:Encephalitis, Viral / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D009205:Myocarditis / Q000276:immunology / Q000821:virology; D019349:Roseolovirus Infections / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins