1. Background
Drug reaction with eosinophilia and systemic symptoms (DRESS) is an uncommon severe cutaneous adverse reaction associated with internal organ involvement, lymphadenopathy, atypical lymphocytosis and eosinophilia. The manifestations are heterogeneous and features of rash and eosinophilia may be occasionally absent, leading to diagnostic difficulties.1, 2 The disease course is typically prolonged and episodes of flares may occur despite drug cessation. Mortality has been reported to be between 2 to 10 percent,3-5 and long-term sequelae of autoimmunity has been reported in survivors.6
The majority of reactions can be attributed to a number of high-risk medications such as allopurinol, aromatic anti-epileptic agents, anti-microbial sulfonamides, vancomycin and minocycline.3 The estimated risk following new prescriptions of aromatic antiepileptic agents is 1-4.5 in 10,000.7 The latency between culprit drug initiation and onset ranges from 2-8 weeks.
Postulated disease mechanism in DRESS include i) pharmacogenetics susceptibility eg. association of HLA- A*3101 in carbamazepine-induced DRESS, HLA-B*5801 in allopurinol-induced DRESS, and HLA-B*1301 in dapsone-induced DRESS.8-10 ii) activation of drug-specific T cells,11 (iii) dysregulation of regulatory cells T cells,12 iv) human herpesvirus reactivation and the subsequent role of anti-viral immune response.13
Reactivation of the human herpesvirus is a known phenomenon of DRESS, occurring in up to 75% of patients.13 HHV6 is the most common agent within the family to be reactivated, occurring between 45-60% depending on detection methodologies.13, 14 Multiple, sequential reactivation of viruses has been observed in up to 30% of cases with a temporal pattern similar to that of graft-versus-host disease.15 Reactivation of HHV6 has been associated with disease flares and severity.14 Fatal DRESS cases have been anecdotally attributed to CMV reactivations.16
Despite these observations, the impact of herpes viral reaction on the clinical course remains largely unknown.17 The primary aim of our study is to examine the impact of viral reactivation on the clinical course and outcomes in a large cohort of DRESS patients and the secondary aim is to explore potential risk factors for viral reactivation.