Occupational trichloroethylene hypersensitivity syndrome: Human herpesvirus 6 reactivation and rash phenotypes

Background: Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational ICE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). Objective: This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. Methods: HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. Results: The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (>= 100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p < 0.01). Positive correlations between HHV6 DNA, TNF-alpha, IFN-gamma, IL-6 and IL-10 were significant (p < 0.05) except for that between HHV6 DNA and IFN-gamma. An increase in HHV6 DNA was positively associated with an increase in TNF-alpha on admission (p < 0.01). HHV6 DNA, the antibody titers, TNF-alpha and IL-10 concentrations were significantly higher in ED than in the non-ED type (p < 0.05). Conclusion: Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.