Association Between Anticonvulsant Hypersensitivity Syndrome and Human Herpesvirus 6 Reactivation and Hypogammaglobulinemia

Abstract

BACKGROUND: Anticonvulsant hypersensitivity syndrome (AHS) is a life-threatening, drug-induced, multiorgan system reaction. The identification of predisposing factors is clearly needed to predict the incidence and outcome of AHS; attention has recently been focused on reactivation of human herpesvirus 6 (HHV-6). OBJECTIVE: To determine whether immunosuppressive conditions that can allow HHV-6 reactivation could be specifically detected in association with the onset of AHS. DESIGN: We analyzed patients with AHS who were treated during 1997-2002. Two groups of patients receiving anticonvulsants served as controls. SETTING: Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan. Patients Ten patients with AHS. MAIN OUTCOME MEASURES: The results of serologic tests for antibody titers for various viruses, including HHV-6, HHV-6 DNA detection by real-time polymerase chain reaction, immunoglobulin levels by turbidimetric immunoassay, IgG subclass levels by nephelometry, and CD19(+) B-cell counts by flow cytometric analysis, were sequentially assessed. RESULTS: Serum IgG levels (mean, 745 mg/dL) and circulating B-cell counts (mean, 88/ micro L) in patients with AHS were significantly decreased at onset compared with control groups (P<.001 and P =.007, respectively). These alterations returned to normal on full recovery. Reactivation of HHV-6 as judged by a greater than 4-fold increase in HHV-6 IgG titers was exclusively detected in most patients with AHS associated with decreased IgG levels and B-cell counts. CONCLUSIONS: A decrease in immunoglobulin levels and B-cell counts can be associated with HHV-6 reactivation and the subsequent onset of AHS. These immunological alterations might be a useful predictor of the development of AHS.