Viral reactivation and clinical outcomes in Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare severe cutaneous adverse drug reaction associated with multi-organ involvement and long-term sequelae. Human herpesviridae species reactivation has been observed, however, risk factors for reactivation and its impact on the clinical course and outcomes is unclear. We aimed to explore the impact of viral reactivation on DRESS on clinical outcomes and to identify potential risk factors for reactivation. This was a retrospective cohort study in an academic medical centre. Cases were validated in-hospital cases of DRESS from 2009 to 2017. Overall, 100 patients fulfilled the probable or definite DRESS case criteria. Ninety-three patients had at least one viral marker tested. Viral reactivation was positive in 39 patients (42%). HHV6, EBV and CMV reactivation occurred in 24 out of 85 cases (28%), 15 out of 87 (17%) cases, and 18 out of 89 (20%) cases respectively. Viral reactivation cases were associated with higher 1-year mortality, dialysis initiation, recurrent flares of disease, and longer hospital stay (all p < 0.05). Risk of inpatient mortality (OR, 5.8; 95% CI, 1.7-20.7; p < 0.01) and 1-year mortality (OR, 10.0, 95% CI, 2.9-34.9; p < 0.01) increased with multiple viral reactivations. Human herpesviridae viral reactivation in DRESS, particularly multiple viral reactivations, is associated with poorer clinical outcomes. Although this study is unable to prove a causal or pathogenic association, routine evaluation of herpesvirus in DRESS should be performed. Further work is needed to identify patients at risk of reactivation and the potential impact of treatment.