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.