Predominant Contribution of CD4 T Cells to Human Herpesvirus 6 (HHV-6) Load in the Peripheral Blood of Patients with Drug-induced Hypersensitivity Syndrome and Persistent HHV-6 Infection

Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse cutaneous drug reaction associated with the reactivation of human herpesvirus 6 (HHV-6). In DIHS, HHV-6 is generally reactivated 2-3 weeks after the onset of a rash, and such reactivation is associated with the flare-up of clinical symptoms (1). The reactivation of HHV-6 usually occurs as a transient event; however, in rare cases HHV-6 DNA continues to be detected long after the onset of the condition, which is sometimes associated with frequent recurrence of clinical symptoms, such as skin rashes. There has been only one report of a case of DIHS involving a persistent HHV-6 infection (2). We report here 3 cases of DIHS in which HHV-6 DNA was detected in the patients' peripheral blood mononuclear cells (PBMC) long after resolution of their DIHS. We also demonstrated that CD4 T cells were the main contributors to the PBMC HHV-6 DNA load throughout the patients' clinical courses, while in the early stages of their conditions CD14+ monocytes and other types of PBMC also harboured HHV-6 DNA.