The role of viral infection in the development of severe drug eruptions

The role of viral infections in the development of drug allergy has recently received increasing attention. Evidence is accumulating that immune responses to drugs can be profoundly influenced by herpesvirus infection that occurs before, concurrent with, or subsequent to drug administration. The current advances in our understanding of the role of viral infections in drug eruptions have been sparked by recent studies on human herpesvirus 6 (HHV-6) reactivation in severe systemic hypersensitivity reactions to drugs, eventually referred to as drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia with systemic symptoms (DRESS). It becomes clear that HHV-6 is not the only herpes virus reactivated during the course of DiHS and other herpes viruses are also reactivated in sequence as shown in graft-versus-host disease (GVHD), which can explain frequent deterioration or several flare-ups of clinical symptoms occurring after withdrawal of the causative drug in DiHS. Here we describe how sequential reactivations of herpesviruses occur during the course of DiHS and discuss how the reactivation events could influence the initiation and maintenance of drug-specific immune responses, resulting in severe immunopathology.