Drug-induced hypersensitivity syndrome (DIHS) / drug reaction with eosinophilia and systemic symptoms (DRESS) is characterized by fever, cutaneous eruptions, hematological abnormalities, multiple organ dysfunction, and reactivation of human herpesviruses such as HHV-6 and CMV. Reactivation of HHV-6 and CMV has been reported to be involved in clinical course of DIHS. In addition, autoimmune diseases such as type 1 diabetes and thyroiditis sometimes develop after resolution of DIHS. We found that quite a few patients harbor high levels (> 1000 copies / 106 PBMC) of HHV-6 DNA in PBMC over 6 months after onset of DIHS. However, it is unclear what effects persistent HHV-6 infection has on DIHS patients in chronic phase. We analyzed clinical symptoms, hematological and biochemical data, reactivation of herpesviruses, expression of serum cytokines (IL-4, IL-5, IL-10, IFN-γ) and soluble IL-2 receptor for 8 DIHS patients with persistent HHV-6 infection and 10 patients with transient HHV-6 infection. Compared to the transient HHV-6 infection group, persistent HHV-6 infection group showed 1) more severe acute phase cutaneous and mucosal eruptions, 2) higher levels of HHV-6 DNA in acute phase, 3) higher rate of CMV reactivation, 4) higher levels of IL-4 in acute phase and higher levels of soluble IL-2 receptor in late phase, 5) higher rate of long-term complications (ie, interstitial nephritis, arthritis, thyroiditis, encephalitis). Persistent HHV-6 infection may have some influence on the pathological and immunological status of DIHS and may be involved in the clinical course and prognosis.

Immunological and clinical features of patients with persistent human herpesvirus 6 infection after drug-induced hypersensitivity syndrome / drug reaction with eosinophilia and systemic symptoms