HHV-6 Drug Induced Hypersensitivity Syndrome

Numerous studies have linked the reactivation of HHV-6 to Drug-Induced Hypersensitivity Syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS), an uncommon but severe cutaneous adverse drug reaction characterized by acute widespread erythmea with high fever, and multi-organ involvement, especially liver dysfunction. However, the specific mechanisms for viral reactivation and modification of the clinical features remain unclear. A small in vivo study in Japan demonstrated that HHV-6 reactivation induces synthesis of proinflammatory cytokines, specifically elevations of TNF-a and IL-6, which may modulate the clinical features of the syndrome (Yoshikawa et al. 2006). Preliminary results from a study in France suggest that the immune response observed in DRESS patients is principally directed against Human Herpesviruses, especially HHV-6 (Descamps 2006). Another study sought to determine whether herpes viruses reactivate from latency in an obligate order in the course of DIHS, and whether herpesviruses contribute to the clinical manifestations of the syndrome. The real time PCR results from patients with severe DIHS  demonstrated that herpesviruses reactivate in a sequential order as described in patients with graft-versus-host disease (GVHD); the sequential herpesvirus reactivation is coincident with the various clinical manifestations in patients with DIHS (Kano et al., 2004).  Finally, a group in Japan retrospectively analyzed reports of DIHS published in medical journals and found that nearly 84% of DIHS patients had HHV-6 reactivation by increase of HHV-6 IgG and/or increase of HHV-6 DNA in the peripheral blood (Aihara 2004).