Infection of herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in acute tonsillitis--histopathological assessment by optical and electron microscopic observation of biopsy specimens of tonsils

Abstract

Infection with HSV or EBV was studied by measuring serum antiviral antibody titers in adults with acute tonsillitis, and results were compared to light and electron microscopy findings of tonsil biopsy specimens. The clinical and laboratory features of acute tonsillitis caused by HSV or EBV were also studied. Subjiects were 42 patients with acute tonsillitis treated at the Department of Otorhinolaryngology at Tokyo Women's Medical University Daini Hospital between August 1997 and March 2000. They had failed to respond to antimicrobial agents prescribed by a physician, and had severe oropharyngeal mucosal lesions, liver dysfunction, skin eruptions, or cervical lymphadenopathy, with hospitalization required because of impaired food intake due to sore throat or deterioration in general condition. Subjects were 24 men (mean age: 30.8 years) and 18 women (mean age: 28.3 years) aged 16 to 78 years (mean: 29.8 years). A underwent, bacteriological and hematology tests and palatine tonsil biopsy specimens were obtained to examine tissue changes by light microscopy and electron microscopy due to detect HSV antigen by immunohistochemistry and EBV nucleic acids by EBV-encoded small nuclear RNA 1 and 2 (EBER) in situ hybridization (ISH). Among patients, the serum antiviral antibody profile indicated that 4 (9.5%) had acute tonsillitis due to primary HSV infection and 5 (11.9%) had acute tonsillitis due to primary EBV infection. The findings characteristic of acute tonsillitis due to primary HSV infection included stomatitis, skin eruptions, atypical lymphocytes, and liver dysfunction. Findings characteristic of acute tonsillitis due to primary EBV infection included petechiae of the soft palate, an increase of lymphocytes, atypical lymphocytes, and liver dysfunction. At the initial test, serum anti-HSV antibody was positive in 14 patients (33.3%), and more than half had no history of prior infection. Anti-EBNA antibody was positive in 32 (76.2%), and many had been infected previously. It should be noted that a decrease in positive HSV antibody means that acute tonsillitis due to primary HSV infection is not uncommon in adults and is expected to increase steadily. Light microscopy revealed histological changes in 2 patients. HSV antigen was positive in 2 (50%) with acute tonsillitis due to primary HSV infection, while EBER cells were positive in 5 (100%) with acute tonsillitis due to primary EBV infection, so special staining of the tissues was found to be useful. Electron microscopy failed to detect viral particles in ultrathin sections and no differences were seen in morphological changes or tissue damage between patients with positivity for HSV antigen and with EBER-positive cells. Detection of HSV antigen and EBV nucleic acids in pathological specimens from patients with acute tonsillitis requires careful judgment, but is considered useful for making an early diagnosis and for making a diagnosis in patients without an increase of the antiviral antibody titer and in those with reinfection or reactivation. Pathological examination (including special staining) and careful observation of clinical features may help to identify HSV or EBV infection and allow decisions to be made with regard to the therapeutic strategy and prevention of complications.