title: Evidence for human herpesvirus-6B infection of regulatory T-cells in acute systemic lymphadenitis in an immunocompetent adult with the drug reaction with eosinophilia and systemic symptoms syndrome: a case report.
abstract: We describe a fatal case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with human herpesvirus-6B (HHV-6B)-associated lymphadenitis and virus-associated hemophagocytic syndrome triggered by an over-the-counter medication to treat respiratory and influenza-like symptoms. Histologically, the structure of the lymph node was disrupted with infiltration of large lymphocytes carrying intranuclear acidophilic inclusion bodies. Immunohistochemistry and real-time PCR analysis revealed that these large lymphocytes were positive for HHV-6B. Numerous HHV-6 particles were detected in the inclusion body of the lymphocytes by electron microscopy. Interestingly, immunohistochemistry revealed that HHV-6B-infected cells in the lymph node were CD3(+), CD4(+), CD25(+), and FoxP3(+) T cells, indicating a phenotypic resemblance to regulatory T-cells. This case provides direct evidence of HHV-6 infection in CD25(+)/FoxP3(+) T cells in a case of acute lymphadenitis of DRESS syndrome, suggesting a significant role of HHV-6 infection of regulatory T-cells in the pathogenesis of DRESS syndrome.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Sohtaro
authors.initials: S
authors.lastname: Mine
authors.affiliation: Department of Pathology, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan.
authors.forename: Koyu
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Fukumoto
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Kataoka
authors.affiliation: Department of Microbiology and Immunology, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu City, Gifu 501-1196, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Department of Diagnostic Pathology, Nara Medial University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Ohbayashi
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan.
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Electronic address: katano@nih.go.jp.
authors.forename: Harutaka
authors.initials: H
authors.lastname: Katano
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D063926:Drug Hypersensitivity Syndrome / Q000150:complications*; D004583:Electrons; D017809:Fatal Outcome; D051858:Forkhead Transcription Factors / Q000032:analysis; D015654:Herpesvirus 6, Human / Q000302:isolation & purification*; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007181:Inclusion Bodies, Viral / Q000648:ultrastructure; D008198:Lymph Nodes / Q000473:pathology; D008199:Lymphadenitis / Q000175:diagnosis* / Q000209:etiology*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000473:pathology; D008853:Microscopy; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D019349:Roseolovirus Infections / Q000150:complications / Q000175:diagnosis* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000473:pathology / Q000821:virology*
chemical_list: D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: DRESS syndrome; Drug-induced hypersensitivity syndrome; Human herpesvirus 6; Lymphadenitis; Over-the-counter medicine; Regulatory T-cells