Recent Advances in Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms

Drug-induced hypersensitivity syndrome (DIHS), also termed as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multiorgan systemic reaction characterized by a close relationship with the reactivation of herpes virus. Published data has demonstrated that among patients with DIHS/DRESS, 75-95% have leukocytosis, 18.2-90% show atypical lymphocytes, 52-95% have eosinophilia, and 75-100% have hepatic abnormalities. Histologically, eosinophils were observed less frequently than we expected (20%). The mainstay of DIHS/DRESS treatment is a moderate dose of systemic corticosteroids, followed by gradual dose reduction. In this review, we will emphasize that elevations in the levels of several cytokines/chemokines, including tumor necrosis factor- (TNF-) alpha and the thymus and activation-regulated chemokine (TARC/CCL17), during the early stage of disease, are good markers allowing the early recognition of HHV-6 reactivation. TNF-alpha and TARC levels also reflect therapeutic responses and may be useful markers of the DIHS disease process. Recently, the pathogenic mechanism of T-cell activation triggered by human leukocyte antigen- (HLA-) restricted presentation of a drug or metabolites was elucidated. Additionally, we recently reported that dapsone would fit within the unique subpocket of the antigen-recognition site of HLA-B*13:01. Further studies will render it possible to choose better strategies for DIHS prevention and therapy.