Drs. Ishida and Shiohara from Kyorin University in Tokyo have published an important new study on the dynamics of herpesvirus reactivations during and after severe drug reactions. We asked them their thoughts on the implications of their findings.
Q: What are your future plans for research on the role of herpesviruses in drug hypersensitivity reactions?
A: Our aim is to elucidate the mechanism of how herpesvirus infection can be involved in the development of drug hypersensitivity reactions. There are several possibilities. First, resident memory T cells specific for herpes virus cold be activated in a cross-reactive manner by drug, whose concept is known as heterologous immunity. Second, the subpopulation of monocytes, particularly proinflammatory monocytes, which has been shown to mediate an anti-viral role by sensing herpes virus infection and producing cytokines and chemokines, could be depleted by their infection with herpes virus, thereby causing expansions of regulatory T cells and subsequent reactivation of several herpes viruses. We have recently focused on the second possibility.
Q: Will your group begin administering steroids only to EBV+ patients in the future?
A: We used corticosteroids for many patients with severe drug eruptions regardless of whether they are positive for EBV-DNA. Although our study demonstrates the beneficial role of EBV-DNA for the prevention to progression to TEN, this result should be confirmed by a large-scale of study. So far we suppose that corticosteroids given to patients with severe drug eruption may serve to ameliorate tissue damage and reduce subsequent development of sequelae.
Q: Will you consider EBV and CMV/HHV-6 specific antiviral therapy for these patients?
A: CMV reactivation occurring during and after severe drug eruptions should be treated by ganciclovir (or valganciclovir), because CMV diseases are often fatal. However, we usually do not treat EBV and HHV-6 reactivation, because there is no standard treatment modality for reducing the viral loads and they do not develop severe clinical symptoms. In addition, because we have some concern that the use of these antiviral agents may cause additional sensitization to these drugs in the setting of drug eruption, we do not specifically treat EBV and HHV-6 reactivations.
Q: What was the difference in outcome between the DIHS/DRESS patients in the steroid vs non-steroid group? (In other words, there were four deaths. Were they all in the steroid treated group?)
A: All deaths in acute disease phase were observed in patients treated with systemic corticosteroids. In contrast, however, many sequelae in the resolution stage can be preferentially observed in the non-steroid group. That’s why we need more information about short- and long-term outcomes in these patients treated with or without corticosteroids.