Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome

Abstract

Background Drug‐induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after a 3–6‐week exposure to certain drugs, including anticonvulsants. There are some reports showing that serum IgG levels often decrease at the early stage of DIHS. Reactivation of human herpesvirus (HHV)‐6 has been reported in patients with DIHS, and some other DIHS patients showed reactivation of cytomegalovirus (CMV) or Epstein–Barr virus (EBV). Objectives To determine whether reactivation of HHV‐6, HHV‐7, CMV and/or EBV occurs in patients with DIHS. Methods Titres of IgG and IgM antibodies to HHV‐6 and HHV‐7 were determined using an indirect immunofluorescence antibody assay on admission and at various times after admission. Anti‐CMV IgG and IgM antibody titres and anti‐EBV capsid antigen IgG, IgA, IgM, and EBV nuclear antigen and EBV early antigen IgG titres were determined by enzyme immunoassay. Polymerase chain reaction (PCR) procedures for HHV‐6, HHV‐7, CMV and EBV DNAs were performed using serum samples. Results IgG antibody titres to HHV‐6, HHV‐7, CMV and EBV were increased after the onset in seven, six, seven and two of seven patients, respectively. IgG antibody titres to HHV‐6 and HHV‐7 were elevated simultaneously 21–38 days after the onset. IgG antibody titres to CMV and EBV were elevated 10–21 days after the elevation of HHV‐6 and HHV‐7 antibody titres. PCR showed that HHV‐6, HHV‐7, CMV and EBV DNAs became positive in six, five, seven and two of seven patients, respectively. HHV‐6 and HHV‐7 DNAs were detected 21–35 days after the onset, and CMV DNA was detected 10–21 days after detection of HHV‐6 and HHV‐7 DNAs. Conclusions The present study suggests that in addition to HHV‐6 reactivation, reactivation of HHV‐7, CMV and/or EBV may also occur following drug eruption in some patients with DIHS.