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 TCE 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)-α, interferon (IFN)-γ, 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-α, IFN-γ, IL-6 and IL-10 were significant (p<0.05) except for that between HHV6 DNA and IFN-γ. An increase in HHV6 DNA was positively associated with an increase in TNF-α on admission (p<0.01). HHV6 DNA, the antibody titers, TNF-α and IL-10 concentrations were significantly higher in ED than in the non-ED type (p<0.05).


CONCLUSIONS
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.
Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Electronic address: kamijima@med.nagoya-cu.ac.jp.
Michihiro
M
Kamijima
Hailan
H
Wang
Osamu
O
Yamanoshita
Yuki
Y
Ito
Lihua
L
Xia
Yukie
Y
Yanagiba
Cishan
C
Chen
Ai
A
Okamura
Zhenlie
Z
Huang
Xinxiang
X
Qiu
Xiangrong
X
Song
Tingfeng
T
Cai
Lili
L
Liu
Yichen
Y
Ge
Yingyu
Y
Deng
Hisao
H
Naito
Tetsushi
T
Yoshikawa
Mikiko
M
Tohyama
Laiyu
L
Li
Hanlin
H
Huang
Tamie
T
Nakajima
D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000097:blood*; D063926:Drug Hypersensitivity Syndrome / Q000097:blood / Q000209:etiology* / Q000473:pathology; D005076:Exanthema / Q000139:chemically induced / Q000473:pathology; D005260:Female; D015654:Herpesvirus 6, Human / Q000187:drug effects*; D006801:Humans; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D010641:Phenotype; D011446:Prospective Studies; D019349:Roseolovirus Infections / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D014241:Trichloroethylene / Q000506:poisoning*; D019562:Viral Load; D014775:Virus Activation / Q000187:drug effects; D055815:Young Adult
D016207:Cytokines; D014241:Trichloroethylene
Biomarker; Cytokine; DIHS; DRESS; Drug-induced hypersensitivity syndrome (DIHS); ED; EM; HHV6; Human herpesvirus 6; IFN-γ; IL; LOQ; PBMC; Reactivation; SD; TCA; TCE; TEN; TNF-α; Trichloroethylene; drug reaction with eosinophilia and systemic symptoms; drug-induced hypersensitivity syndrome; erythema multiforme; exfoliative dermatitis; human herpesvirus 6; interferon gamma; interleukin; limit of quantification; peripheral blood mononuculear cell; standard deviation; toxic epidermal necrolysis; trichloroacetic acid; trichloroethylene; tumor necrosis factor alpha