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

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 als...

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Published inNippon Jibi Inkoka Gakkai Kaiho Vol. 104; no. 11; pp. 1093 - 1102_2
Main Author TANAKA, Nobuaki
Format Journal Article
LanguageJapanese
Published Japan The Oto-Rhino-Laryngological Society of Japan, Inc 01.11.2001
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ISSN0030-6622
1883-0854
DOI10.3950/jibiinkoka.104.1093

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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.
AbstractList 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.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.
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.
Author TANAKA, Nobuaki
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References 18) Glickman JN, Howe JG, Steitz JA: Structural analyses of EBER 1 and EBER 2 ribonucleoprotein particles present in Epstein-Barr virus infected cells. J Virol 62: 902-911, 1988.
1) 川名林治: ウイルス感染症の実験室診断の意義. 上竹久雄編, ウイルス学第4版. 理工学社: 495-501, 1992.
3) Evans AS: Infectious mononucleosis and other monolike syndromes. N Engl J Med 286: 836-838, 1972.
12) Beard JS, Fishberg DP, Sau P, Bauer FA, James WD: Ominous tzanck smears in primary herpes simplex virus infection. Arch Dermatol 129: 966-968, 1993.
2) Putto A: Febrile exdative tonsillitis; Viral or streptococcal?. Pediatrics 80: 6-11, 1987.
16) 和田順子: 性感染症 (STD) 病原体と病態単純ヘルペスウイルス. 臨床検査40: 659-662, 1996.
10) Kobayashi R, Takeuchi H, Hasegawa M, Hirai K: Detection of Epstein-Barr virus infection in the epithelial cells and lymphocytes of non-neoplastic tonsils by in situ hybridization and in situ PCR. Arch Virol 143: 803-813, 1998.
14) 白幡雄一, 大西俊郎, 橘敏郎, 馬場千恵子: 伝染性単核球症36例の臨床的検討. 耳展33: 303-310, 1990.
9) Yoda K, Sata T, Kurata T, Aramaki H: Oropharyngotonsillitis Associated With Nonprimary Epstein Barr Virus Infection. Arch Otolaryngial Head Neck Surg 126: 185-193, 2000.
17) 佐多徹太郎, 前田明彦, 佐藤由子, 岩崎琢也, 倉田毅: ヘルペス群ウイルスのin situ hybridization. 病理と臨床11: 203-206, 1993.
20) Niedobitek G, Agathanggelou A, Steven N, Young LS: Epstein-Barr virus (EBV) in infectious mononucleosis; detection of the virus in tonsillar B lymphocytes but not in desquamated oropharyngeal epithelial cells. Mole Pathol 53: 37-42, 2000.
5) Takiuchi Y, Tatsumi E, Shirakawa E, Uchino H: Infectious mononucleosis and Epstei-Barr virus in Japan I. Clinical and Serogical Aspects. 日本血液学会雑誌43: 700-710, 1980.
13) Litwins J, Leibowitz S: Abnormal lymphocytes (virocytes) in virus diseases other than infectious mononucleosis. Acta Haematol 5: 223-231, 1951.
4) Akashi K, Eizuru Y, Sumiyoshi Y, Hara S, Haneda M: Sever infectious mononucleosis like syndromes and primary human herpesvirus 6 infection in an adult. N Engl J Med 329: 168-171, 1993.
11) 床枝康伸, 伊藤純子, 片山啓, 伊藤令子: アデノウイルス3型による有熱性滲出性扁桃炎の臨床的検討. 日本小児科学会雑誌93: 117-126, 1989.
15) 本藤良: 単純ヘルペスウイルス (4) 血清疫学. ウイルス感染症の臨床と病理. 医学書院: 34-37, 1991.
22) Niedobitek G, Herbst H, Young LS, Brooks L, Masucci MG,: Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue. Blood 79: 2520-2526, 1992.
8) 佐多徹太郎, 倉田毅: ウイルス感染症 (2). 病理と臨床6: 203-206, 1988.
24) Endo LH, Ferreria D, Montenegro MC, Pinto GA, Altemani A,: Detection of Epstein-Barr virus in tonsillar of children and the relationship with recurrent tonsillitis. Int J Pediatr Otolaryngol 58: 9-15, 2001.
6) 小川浩司, 山崎嘉司, 橋口一弘: 性行為によって感染した2型単純ヘルペス・ウイルスによる急性扁桃炎. 耳鼻臨床81: 79-83, 1988.
21) Anagnostopoulos I, Hummel M, Kreschel C, Stein H: Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus. Blood 85: 744-750, 1995.
7) 青山友三, 南谷幹夫, 倉田毅: ウイルス感染症検索のための材料採取の方法と検索の仕方. ウイルス感染症の臨床と病理. 医学書院: 1-21, 1991.
25) 新村眞人, 本田まりこ: 性感染症 (STD) 新しい免疫学的検査法・遺伝子診断法単純ヘルペスウイルス. 臨床検査40: 699-701, 1996.
19) 永里弘子, 徳永正義, 小山田誠朋, 山下勝江, 藤崎人美, 他: 病理組織標本におけるEpstei-Barr virus (EBV) の証明法-病理研究室でのin situ hybridzation-. 病理と臨床10: 951-955, 1992.
23) Ikeda T, Kobayasi R, Horiuchi M, Nagata Y, Hasegawa M,: Detection of lymphocytes productively infection with Epstein-Barr virus in non-neoplastic tonsils. J Gen Viro 181: 1211-1216, 2000.
References_xml – reference: 17) 佐多徹太郎, 前田明彦, 佐藤由子, 岩崎琢也, 倉田毅: ヘルペス群ウイルスのin situ hybridization. 病理と臨床11: 203-206, 1993.
– reference: 1) 川名林治: ウイルス感染症の実験室診断の意義. 上竹久雄編, ウイルス学第4版. 理工学社: 495-501, 1992.
– reference: 10) Kobayashi R, Takeuchi H, Hasegawa M, Hirai K: Detection of Epstein-Barr virus infection in the epithelial cells and lymphocytes of non-neoplastic tonsils by in situ hybridization and in situ PCR. Arch Virol 143: 803-813, 1998.
– reference: 22) Niedobitek G, Herbst H, Young LS, Brooks L, Masucci MG,: Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue. Blood 79: 2520-2526, 1992.
– reference: 24) Endo LH, Ferreria D, Montenegro MC, Pinto GA, Altemani A,: Detection of Epstein-Barr virus in tonsillar of children and the relationship with recurrent tonsillitis. Int J Pediatr Otolaryngol 58: 9-15, 2001.
– reference: 8) 佐多徹太郎, 倉田毅: ウイルス感染症 (2). 病理と臨床6: 203-206, 1988.
– reference: 3) Evans AS: Infectious mononucleosis and other monolike syndromes. N Engl J Med 286: 836-838, 1972.
– reference: 12) Beard JS, Fishberg DP, Sau P, Bauer FA, James WD: Ominous tzanck smears in primary herpes simplex virus infection. Arch Dermatol 129: 966-968, 1993.
– reference: 7) 青山友三, 南谷幹夫, 倉田毅: ウイルス感染症検索のための材料採取の方法と検索の仕方. ウイルス感染症の臨床と病理. 医学書院: 1-21, 1991.
– reference: 15) 本藤良: 単純ヘルペスウイルス (4) 血清疫学. ウイルス感染症の臨床と病理. 医学書院: 34-37, 1991.
– reference: 21) Anagnostopoulos I, Hummel M, Kreschel C, Stein H: Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus. Blood 85: 744-750, 1995.
– reference: 5) Takiuchi Y, Tatsumi E, Shirakawa E, Uchino H: Infectious mononucleosis and Epstei-Barr virus in Japan I. Clinical and Serogical Aspects. 日本血液学会雑誌43: 700-710, 1980.
– reference: 6) 小川浩司, 山崎嘉司, 橋口一弘: 性行為によって感染した2型単純ヘルペス・ウイルスによる急性扁桃炎. 耳鼻臨床81: 79-83, 1988.
– reference: 16) 和田順子: 性感染症 (STD) 病原体と病態単純ヘルペスウイルス. 臨床検査40: 659-662, 1996.
– reference: 2) Putto A: Febrile exdative tonsillitis; Viral or streptococcal?. Pediatrics 80: 6-11, 1987.
– reference: 14) 白幡雄一, 大西俊郎, 橘敏郎, 馬場千恵子: 伝染性単核球症36例の臨床的検討. 耳展33: 303-310, 1990.
– reference: 20) Niedobitek G, Agathanggelou A, Steven N, Young LS: Epstein-Barr virus (EBV) in infectious mononucleosis; detection of the virus in tonsillar B lymphocytes but not in desquamated oropharyngeal epithelial cells. Mole Pathol 53: 37-42, 2000.
– reference: 23) Ikeda T, Kobayasi R, Horiuchi M, Nagata Y, Hasegawa M,: Detection of lymphocytes productively infection with Epstein-Barr virus in non-neoplastic tonsils. J Gen Viro 181: 1211-1216, 2000.
– reference: 19) 永里弘子, 徳永正義, 小山田誠朋, 山下勝江, 藤崎人美, 他: 病理組織標本におけるEpstei-Barr virus (EBV) の証明法-病理研究室でのin situ hybridzation-. 病理と臨床10: 951-955, 1992.
– reference: 9) Yoda K, Sata T, Kurata T, Aramaki H: Oropharyngotonsillitis Associated With Nonprimary Epstein Barr Virus Infection. Arch Otolaryngial Head Neck Surg 126: 185-193, 2000.
– reference: 25) 新村眞人, 本田まりこ: 性感染症 (STD) 新しい免疫学的検査法・遺伝子診断法単純ヘルペスウイルス. 臨床検査40: 699-701, 1996.
– reference: 18) Glickman JN, Howe JG, Steitz JA: Structural analyses of EBER 1 and EBER 2 ribonucleoprotein particles present in Epstein-Barr virus infected cells. J Virol 62: 902-911, 1988.
– reference: 13) Litwins J, Leibowitz S: Abnormal lymphocytes (virocytes) in virus diseases other than infectious mononucleosis. Acta Haematol 5: 223-231, 1951.
– reference: 4) Akashi K, Eizuru Y, Sumiyoshi Y, Hara S, Haneda M: Sever infectious mononucleosis like syndromes and primary human herpesvirus 6 infection in an adult. N Engl J Med 329: 168-171, 1993.
– reference: 11) 床枝康伸, 伊藤純子, 片山啓, 伊藤令子: アデノウイルス3型による有熱性滲出性扁桃炎の臨床的検討. 日本小児科学会雑誌93: 117-126, 1989.
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Snippet 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...
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pubmed
jstage
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SubjectTerms Acute Disease
acute tonsillitis
Adolescent
Adult
Aged
electron microscopy
Epstein-Barr Virus Infections
Female
Herpes Simplex
Herpesvirus 4, Human - isolation & purification
Humans
immunohistochemistry
in situ hybridization
Male
Middle Aged
Palatine Tonsil - pathology
Simplexvirus - isolation & purification
Tonsillitis - pathology
Tonsillitis - virology
viral infection
Subtitle Histopathological Assessment by Optical and Electron Microscopic Observation of Biopsy Specimens of Tonsils
Title Infection of Herpes Simplex Virus (HSV) and Epstein-Barr Virus (EBV) in Acute Tonsillitis
URI https://www.jstage.jst.go.jp/article/jibiinkoka1947/104/11/104_11_1093/_article/-char/en
https://www.ncbi.nlm.nih.gov/pubmed/11766395
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Volume 104
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ispartofPNX Nippon Jibiinkoka Gakkai Kaiho, 2001/11/20, Vol.104(11), pp.1093-1102_2
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