A Clinical Observation of Drug Hypersensitivity Syndrome and Serologic and Molecular Genetic Analyses of Human Herpesvirus-6 Reactivation

Kim, Jae Wang; Kim, Jin Seok; Kim, Kwang Joong

Abstract

BACKGROUND
Drug hypersensitivity syndrome (DHS) is a life-threatening reaction that appears after prolonged exposure to certain drugs. Unlike usual drug eruptions, DHS typically represents protracted a clinical course, slow resolution and a higher mortality rate. Recently, several studies have provided evidence to show that the reactivation of human herpesvirus-6 (HHV-6) is implicated in the pathogenesis of DHS. Until now, the study of the relationship of HHV-6 with DHS has rarely been presented in Korea. OBJECTIVE: We performed this study in order to determine the possibility of reactivation of HHV-6 in patients with DHS. METHODS: A clinical survey was performed retrospectively using the available medical records of 8 DHS cases. Concurrently, the histopathologic, serologic and molecular genetic analyses of the preserved specimens of the DHS patients were conducted, and the results were compared with 3 cases of another type of drug eruption. RESULTS: 1. Mean time of onset of clinical disease following the institution of a new drug was 21.8 days. Time from appearance of first skin lesion to the initiation of therapy (time to treat) was 6.1 days. The most common offending drugs were allopurinol (37.5%) and anti-convulsants (50%), including lamotrigine. The clinical outcome was as follows; recovery in 7 patients and transfer in one patient. 2. The clinical features of patients with DHS were as follows; widespread skin rash (100%), histopathologic findings compatible with drug hypersensitivity (100%), toxic hepatitis (100%), cholestatic injuries (37.5%), renal dysfunction (37.5%), drug fever (100%), leukocytosis (100%), peripheral eosinophilia (100%), lymphadenopathy (62.5%), and atypical lymphoid cells on a peripheral blood smear (62.5%). 3. Anti-HHV-6 IgM antibodies were detected in 2 patients (25%). Reactivation of HHV-6, as judged by a greater than 4-fold increase in anti-HHV-6 IgG titers, was detected in 5 cases (62.5%) of serum samples obtained 3 weeks after onset. 4. HHV-6B genome was detected by polymerase chain reaction (PCR) in 3 patients (37.5%) in the serum samples obtained 2 weeks after onset. At the second weeks, it was detected in the skin lesions of 4 patients (50%) and in the normal skin specimen of one case (12.5%). In one case of a patient without DHS, HHV-6B DNA was found by PCR in the serum sample at the second weeks. CONCLUSION: Several cases of DHS in Korea were associated with the reactivation of HHV-6. Accordingly, HHV-6 reactivation seems to play a potential role in the development of DHS in susceptible patients.