title: Drug-induced hypersensitivity syndrome associated with reactivation of human herpesvirus 6 presenting with severe hepatic injury.
abstract: Little is known about the pathophysiology of liver complication seen in drug-induced hypersensitivity syndrome (DIHS). We describe herein a 32-year-old Japanese man with DIHS due to salazosulfapyridine (SASP) associated with reactivation of human herpesvirus 6 (HHV-6) presenting with severe acute hepatic injury. The patient, with a 1-year history of ulcerative colitis (UC), presented with high fever and abnormally elevated liver enzymes. Six weeks prior to his symptoms, prednisolone (PSL) and SASP had been started because of UC aggravation. Besides fever and liver dysfunction, the appearance of atypical lymphocytes together with eosinophils and generalized erythematous maculopapular skin rash developed sequentially, and a diagnosis of DIHS was established. Despite cessation of SASP and increased dose of PSL, his initial abnormalities continued, and biphasic second alanine aminotransferase (ALT) flare with deep jaundice worsened. Based on the significant increase in the titer of HHV-6 IgG antibodies at the second peak of ALT level without HHV-6 IgM antibody elevation, strongly suggesting reactivation of the virus, HHV-6 was first considered to directly contribute to the deterioration of liver function. However, extensive histological analysis of the liver led to the realization that the cause of the DIHS liver injury was essentially drug-related hepatotoxicity induced by SASP, causing wide-ranging damage to both the hepatocytes and cholangiocytes.
authors.affiliation: Department of Internal Medicine, Social Insurance Central General Hospital, 3-22-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan. h.miura@shahochu.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miura
authors.affiliation: Department of Pathology, Yachiyo Medical Center, Tokyo Women's Medical University, 477-96 Ohwadashinden, Yachiyo, Chiba, 276-8524, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Department of Internal Medicine, Social Insurance Central General Hospital, 3-22-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Department of Pathology, Social Insurance Central General Hospital, 3-22-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Kitamura
authors.affiliation: Department of Internal Medicine, Social Insurance Central General Hospital, 3-22-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Internal Medicine, Social Insurance Central General Hospital, 3-22-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takazoe
keywords: Drug-induced hypersensitivity syndrome (DIHS); Drug-induced liver injury; Reactivation of human herpesvirus 6 (HHV-6); Salazosulfapyridine (SASP); Ulcerative colitis (UC)