Histiocytic necrotizing lymphadenitis in children : association of human herpes virus 8 and Epstein Barr virus

소아에서의 조직구성 괴사성 림프절염 : human herpesvirus 8과 Epstein Barr virus와의 연관성

  • Kim, Hyun A (Department of Pediatrics, College of Medicine, Inje University) ;
  • Chung, Ju-Young (Department of Pediatrics, College of Medicine, Inje University) ;
  • Kim, Sang Woo (Department of Pediatrics, College of Medicine, Inje University) ;
  • Lim, Sung Jig (Department of Pathology, College of Medicine, Inje University) ;
  • Shin, Haeng Seop (Division of AIDS, National Institute for Health)
  • 김현아 (인제대학교 의과대학 소아과학교실) ;
  • 정주영 (인제대학교 의과대학 소아과학교실) ;
  • 김상우 (인제대학교 의과대학 소아과학교실) ;
  • 임성직 (인제대학교 의과대학 병리학교실) ;
  • 신행섭 (국립보건연구원 에이즈종양바이러스팀)
  • Received : 2006.04.14
  • Accepted : 2006.06.13
  • Published : 2006.08.15

Abstract

Purpose : The aims of this study were to analyze the clinical characteristics of children with Kikuchi's disease(KD) at a medical center and to investigate the etiologic role of human herpesvirus 8(HHV 8) or Epstein-Barr virus(EBV) in children with KD. Methods : Twenty six children who were diagnosed as KD between Jan. 1998 and Dec. 2005 were included. Medical records were reviewed on the clinical characteristics of children with KD. Follow up data were collected by chart review and telephone contact. Polymerase chain reaction(PCR) was performed in order to detect HHV 8 DNA, and in situ hybridization(ISH) was perfomed in order to detect EBV RNA from 20 lymph node tissues. Results : There were 15 girls and 11 boys with a mean age of 13 years. Posterior cervical lymph nodes were involved in 72 percent(18/25) of the patients. Extracervical lymphadenopathy was associated in one patient. Fever was an associated symptom in 31 percent(8/26) of the patients. Leukopenia was observed in six (46 percent) patients. The cervical lymphadenopathy usually resolved spontaneously within 6 months. Only one patient had a recurrence of lymphadenopathy with fever during follow-up. No children with KD in our series developed systemic lupus erythematosus. HHV 8 DNA was not amplified by nested PCR in any of the cases, and all cases were negative for EBV RNA by ISH. Conclusion : KD should be differentiated as a cause of cervical lymphadenopathy in children. HHV 8 and EBV may not play major causative roles in KD in children.

목 적 : KD는 주로 동양의 젊은 성인 여성에게서 경부 림프절 종대로 발현하는 것이 특징이며 수개월 내에 자연 치유되는 양호한 경과를 가지는 질환이다, 저자들은 KD로 진단된 소아환아의 임상적 특징을 알아보고, 환아들의 림프절 조직에서 바이러스 검출을 시도하여 KD와 HHV 8, EBV와의 연관성을 알아보기 위하여 본 연구를 시행하였다. 방 법 : 인제대학교 상계백병원에서 1998년 1월부터 2005년 12월까지 KD로 진단되어 치료받은 17세 이하 소아 26례를 대상으로 임상적 특징을 고찰하였다. 병력지 고찰을 통하여 후향적으로 분석하였고 추적 조사는 외래 병력 기록지와 전화 방문을 통하여 분석하였다. KD 환아의 림프절 조직으로부터 DNA를 추출하여 HHV 8 DNA를 검출하기 위해 PCR, EBV RNA를 검출하기 위해 ISH가 시행되었다. 결 과 : KD로 진단된 26명 중 남아 11례, 여아 15례로 성비는 1:1.4였고, 평균 연령은 13세였다. 환아의 연도별 분포는 2000년에 7례로 가장 많았으며, 여름에 가장 많이 진단되었다. 주증상은 발열(8/26)과 림프절의 동통(11/26)으로 발열의 기간은 평균 7.3일 이었다. 목빗근 뒷부위의 림프절 종대가 72%(18/24)였고 1례에서 경부 이외의 림프절 종대로 나타났다. 림프절의 크기는 $1cm{\times}1cm$에서부터 $6cm{\times}6cm$까지로 다양하게 나타났다. 백혈구 감소가 46%(6/13)에서 있었고 적혈구 침강 속도상승(>20 mm/hr)이 62%(8/13)에서 나타났다. 검체 확보가 가능하였던 20례 모두에서 HHV 8 DNA는 검출되지 않았으며, ISH를 이용한 EBV RNA 검사 결과도 음성이었다. KD 26례 모두 임상 경과는 양호하였으며, 1례(4%)만이 추적 중 발열과 함께 재발하였다. 전신성 홍반성 루프스를 포함한 결체 조직 질환으로의 이환은 관찰되지 않았다. 결 론 : KD는 소아에서 드물지 않게 발생하므로, 림프절 종대를 호소하는 환아에서 감별 진단에 포함되어야 한다. HHV 8과 EBV는 소아에서 진단된 KD의 원인 병원체로 작용할 가능성이 적을 것으로 생각된다.

Keywords

References

  1. Kikuchi M. Lymphadenitis showing focal reticulum cell hyperplasia with nuclear debris and phagocytosis. Acta Haematol Jpn 1972;35:379-80
  2. Fujimoto Y, Kojima Y, Yamaguchi K. Cervical subacute necrotizing lymphadenitis. Naika 1972;30:920-7
  3. Dorfman RF, Berry GJ. Lymphadenitis : an analysis of 108 cases with emphasis on differential diagnosis. Semin Diagn Pathol 1988;5:329-45
  4. Imamura M, Ueno H, Mastuura A, Kamiya H, Suzuki T, Kikuchi K, et al. An ultrastructural study of subacute necrotizing lymphadenitis. Am J Pathol 1982;107:292-9
  5. Chua SH, Giam YC, Sim CS. Systemic lupus erythematosus with erythema multiform-like lesions and histiocytic necrotizing lymphadenitis-a case report. Ann Acad Med Singapore 1996;25:599-661
  6. Viguer JM, Jimenez-Heffernan JA, Perez P, Lopez-Ferrer P, Gonzalez-Peramoto P, Vicandi B. Fine needle aspiration cytology of Kikuchi's lymphadenitis; a report of ten cases. Diagn Cytopathol 2001;25:220-4. https://doi.org/10.1002/dc.2042
  7. Asano S, Akaike Y, Muramatsu T, Wakasa H, Yshida H, Konou R, et al. Necrotizing lymphadenitis : A clinicopathological and immunohistochemical study of four familial cases and five recurrent cases. Virchows Arch A Pathol Anat histopathol 1991;418:215-23 https://doi.org/10.1007/BF01606059
  8. Chiu CF, Chow KC, Lin TY, Tsai MH, Shin CM, Chen LM. Virus infection in patients with histiocytic necrotizing lymphadenitis in Taiwan : detection of Epstein-Barr virus, type 1 human T-cell lymphtrophic virus, and parvovirus B 19. Am J Clin Pathol 2000;113:774-81 https://doi.org/10.1309/1A6Y-YCKP-5AVF-QTYR
  9. Krueger GR, Huetter ML, Rojo J, Romero M, Cruz-Ortiz H. Human herpesvirues HHV-4(EBV) and HHV-6 in Hodgkin's and Kikuchi's diseases and their relation to proliferation and apoptosis. Anticancer Res 2001;21:2155-61
  10. Kikuchi M, Yoshizumi T, Nakamura H, Necrotizing lymphadenitis: Possible acute toxoplasmic infection. Virchows Arch A Pathol Anat Histol 1977;376:247-53 https://doi.org/10.1007/BF00432400
  11. Cho KJ, Lee SS, Khang SK. Histiocytic necrotizing lymphadenitis. A clinico-pathologic study of 45 cases with in situ hybridization for Epstein-Barr virus and hepatitis B virus. J Korean Med Sci 1996;11:409-14 https://doi.org/10.3346/jkms.1996.11.5.409
  12. George TI, Jones CD, Zehnder JL, Warnke RA, Dorfman RF. Lack of human herpesvirus 8 and Epstein-Barr virus in Kikuchi's histiocytic necrotizing lymphadenitis. Hum Pathol 2003;34:130-5 https://doi.org/10.1053/hupa.2003.11
  13. Chung JY, Kim SW, Han TH, Lim SJ. Detection of the Bartonella henselae gene sequence in lymph node of children with Kikuchi's disease. Pediatrics 2005;115:1112
  14. Huh J, Kang GH, Gong G, Kim SS, Ro JY, Kim CW. Kaposi's sarcoma associated herpesvirus in Kikuchi's disease. Hum Pathol 1998;29:1091-6 https://doi.org/10.1016/S0046-8177(98)90419-1
  15. Chadburn A, Cesarman E, Nador RG, Liu YF, Knowles DM. Kaposi's sarcoma associated herpesvirus sequences in benign lymphoid proliferation not associated with human immunodeficiency virus. Cancer 1997;80:788-97 https://doi.org/10.1002/(SICI)1097-0142(19970815)80:4<788::AID-CNCR18>3.0.CO;2-P
  16. Han TH, Chung JY, Kim SW. Seroprevalence of Human Herpesvirus 8 in children in Seoul, Korea. Pediatr Infect Dis J 2005;24:476
  17. Andreoni M, Sarmati L, Nicastri E, El Sawaf G, El Zalabani M, Uccella I, et al. Primary human herpesvirus 8 infection in immunocompetent children. JAMA 2002;287: 1295-300 https://doi.org/10.1001/jama.287.10.1295
  18. Bigoni B, Dolcetti R, de Lellis L, Carbone A, Boiocchi M, Cassai E, et al. Human Herpesvirus 8 is present in the lymphoid system of healthy persons and can reactivate in the course of AIDS. J Infect Dis 1996;173:542-9 https://doi.org/10.1093/infdis/173.3.542
  19. Tsang WYW, Chan JKC, Ng CS. Kikuchi's lymphadenitis disease. A morphologic analysis of 75 cases with special reference to unusual features. Am J Surg Pathol 1994;18: 219-31 https://doi.org/10.1097/00000478-199403000-00001
  20. Kuo TT. Kikuchi's disease(histiocytic necrotizing lymphadenitis). A clinicopathological study of 79 cases with an analysis of histologic subtypes, immunohistology and DNA ploidy. Am J Surg Pathol 1995;19:798-809 https://doi.org/10.1097/00000478-199507000-00008
  21. Kim KH, Jung SH, Park C, Choi IJ. Subacute necrotizing lymphadenitis. A collective clinicopathological and immunohistochemical study. Yonsei Med J 1992;33:32-40 https://doi.org/10.3349/ymj.1992.33.1.32
  22. Hong JY, Bae SH, Kim WS. Clinical features of subacute necrotizing lymphadenitis in children. Korean J Pediatr 2002;45:994-9
  23. Ohshima K, Shimazaki K, Kume T, Suzumiya J, Kanda M, Kikuchi M. Perforin and fas pathway of cytotoxic T cells in histiocytic necrotizing lymphadenitis. Histopathology 1998;33:471-8 https://doi.org/10.1046/j.1365-2559.1998.00532.x
  24. Takakuwa T, Ohnuma S, Koike J, Hoshikawa M, Koizumi H. Involvement of cell-mediated killing in apoptosis in histiocytic necrotizing lymphadenitis(Kikuchi-Fujimoto's disease). Histopathology 1996;28:41-8 https://doi.org/10.1046/j.1365-2559.1996.267310.x
  25. Lerosy Y, Lecler-Scarcella V, Francois A, Guitrancourt JA. A pseudo-tumoral form of Kikuchi's disease in children : a case report and review of the literature. Int J Pediatr Otorhinolaryngol 1998;45:1-6 https://doi.org/10.1016/S0165-5876(98)00027-5
  26. Garcia CE, Girdhar-Gopal HV, Dorfman DM. Kikuchi- Fujimoto disease of the neck. Ann Otol Rhinol Laryngol 1993;102:11-5 https://doi.org/10.1177/000348949310200103
  27. Norris A, Krasinskas A, Salhany K, Gluckman S. Kikuchi- Fujimoto disease : a benign cause of fever and lymphadenopathy. Am J Med 1996;101:401-5 https://doi.org/10.1016/S0002-9343(96)00231-8
  28. Turner RR, Martin J, Dorfman RF. Necrotizing lymphadenitis; a study of 30 cases. Am J Surg Pathol 1983;7:115- 23 https://doi.org/10.1097/00000478-198303000-00001
  29. Buchino JJ, Jones VJ. Fine needle aspiration in the evaluation of children with lymphadenopathy. Arch Pediatr Adolesc Med 1994;148:1327-30 https://doi.org/10.1001/archpedi.1994.02170120089017
  30. Ponder TB, Smith D, Ramzy I. Lymphadenopathy in children and adolescents : Role of fine-needle aspiration in management. Cancer Detect Prev 2000;24:228-33
  31. Eisner MD, Amory J, Mullaney B, Tierney LJ, Boner S, Necrotizing lymphadnitis associated with systemic lupus erythematosus. Semin Arthritis Rheum 1996;26:477-82 https://doi.org/10.1016/S0049-0172(96)80028-X
  32. Jang YJ, Park KH, Seok HJ. Management of Kikuchi's disease using glucocorticoid. J Laryngol Otol 2000;114:709- 11
  33. O'Neill D, O'Gray J, Varind S. Child fatality associated with pathological fatures of histiocytic necrotizing lymphadenitis(Kikuchi-Fujimoto disease). Pediatr Pathol Lab Med 1998;18:79-88 https://doi.org/10.1080/107710498174245