HHV-6 has long been associated with drug hypersensitivity reaction syndromes such as DIHS/DRESS. However, the specific mechanism of this relationship has yet to be fully elucidated, and to date there have been no widely accepted biomarkers of the DIHS/DRESS disease process. In a recent study from Japan, a serum TNF-a level of 12 pg/mL, CRP level of 7 mg/dl, and LDH level of 600 U/L were found to be sufficient for prediction of HHV-6 reactivation in this patient population. The TNF-a threshold was particularly correlated with HHV-6 DNA detection, and additional data suggest IL-6 and TNF-a may be good indicators of DIHS/DRESS disease progression overall. While elevated TNF-a detected at the early onset of disease is a strong indicator for the early recognition of HHV-6 reactivation, this finding also reflects important therapeutic information that could be used as an early diagnostic marker of DIHS/DRESS. In addition, IL-6 was found to be a good marker to differentiate DIHS from erythema multiforme.
Although several herpesviruses have been shown to reactivate with DIHS/DRESS, HHV-6 is the most common, and in fact HHV-6 reactivation is part of the criteria for diagnosis of Drug Induced Hypersensitivity Disorder or DIHS in Japan. The authors point out that the mortality rate of DIHS/DRESS is in the range of 2-14%, but that the pathogenesis has never been fully elucidated. Some suspect that the late “flare” of symptoms and organ failure in DIHS/DRES may be due HHV-6 reactivation, exacerbated in part by the high dose steroids that are typically administered. Recently, Vincent Descamps announced that he plans a trial of antiviral therapy in DRESS patients.