Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis (HNL), is a self-limited disease characterized by cervical lymphadenopathy and fever. The etiology of KFD remains unknown; however, the self-limiting nature of HNL suggests the cause of this disease could be viral infection. For this reason, several viruses have been evaluated as possible etiologies of HNL, including Epstein-Barr virus (EBV), human herpesvirus 6 (HHV6), human herpesvirus 8 (HHV8), and cytomegalovirus (CMV). The aim of this study was to examine the relationship of EBV and HHV6 to HNL.

Data pertaining to 51 cases with biopsy-confirmed HNL were collected between January 1999 and December 2005, from the Department of Pathology, College of Medicine, Pusan National University, Busan, Korea. The clinical records-including data regarding age, gender, duration of fever, and lymph node involvementwere reviewed retrospectively. The in situ hybridization (ISH) assay was performed by EBER PNA probe (Dako, Capinteria, CA, USA), and immunohistochemistry testing was performed with anti-HHV type 6 monoclonal antibodies (Chemicon, Temecula, CA, USA).

The HNL patients in this study were 24 males and 27 females, ranging in age from seven to 61 years (median: 25.9). ISH for EBV was positive in 8/51 (15.7%) biopsies, and immunohistochemistry for HHV6 was positive in 15/51 (29.4%) biopsies. Serologic analysis of EBV IgM was performed in 23 cases; only one patient was positive for EBV IgM and EBV ISH.

Our study could not provide supportive evidence of a viral pathogenesis for HNL; therefore, cases of HNL may not have a dominant viral cause. However, some rare exceptional cases may have been caused by viral infection.