Investigation of causes of FUO (fever of unknown origin) in children

소아 불명열 원인에 대한 고찰

  • Park, Hyun Seok (Department of Pediatrics, College of Medicine, Pusan National University) ;
  • Im, Sun Ju (Department of Pediatrics, College of Medicine, Pusan National University) ;
  • Park, Su Eun (Department of Pediatrics, College of Medicine, Pusan National University)
  • 박현석 (부산대학교 의과대학 소아과학교실) ;
  • 임선주 (부산대학교 의과대학 소아과학교실) ;
  • 박수은 (부산대학교 의과대학 소아과학교실)
  • Received : 2006.07.28
  • Accepted : 2006.09.27
  • Published : 2006.12.15

Abstract

Purpose : The causes of prolonged fever have changed during the years and are influenced by age, geographic location and availability of diagnostic facilities/techniques. The aim of the present study was to determine the causes of prolonged fever, to know the proportion and outcomes of undiagnosed children. Methods : We reviewed patients with fever persisting for more than 2 weeks in duration, with documented temperatures of $38^{\circ}C$ on several occasions, or uncertain diagnosis after intensive study of 1 week duration in other hospitals who were admitted to Pusan National University Hospital during the period from July 1999 to June 2004. Results : Fifty-four (59.0 percent) were boys and thirty-seven (41 percent) were girls. Forty-six cases were less than 6 years and 45 cases were more than 6 years; the mean age was $6.48{\pm}6.56years$. In 62 cases (68.1 percent), the fever had persisted for 2 to 3 weeks before admission and in 26 cases (28.6 percent), had lasted longer than a month. Final diagnosis had been reached in 66 of 91 children (72.5 percent). The most common cause was infection (38/91), followed by collagen vascular disease (12/91), immune deficiency (3/91), neoplasia (2/91), and miscellaneous disease. Tuberculosis was the most common infectious cause. The causes of fever were not revealed in 25 cases. Outcome on discharge were as follows; 77 cases (84.6 percent) were improved, 10 cases (11.0 percent) discharged without improvement and 4 cases (4.4 percent) expired. Conclusion : The most common cause of prolonged fever in Korean children remains infection, but the incidence of infection was decreased as compared with previous studies. Tuberculosis is the most common among infectious causes. As Kikuchi disease (subacute necrotizing lymphadenitis) represented a significant cause of prolonged fever, it should be considered if a patient has neutropenia with lymphadenopathy. Undiagnosed patients with prolonged fever (27.5 percent) have increased over previous studies.

서 론 : 소아 불명열의 원인은 수년 동안 변해 오고 있으며 과거보다 각종 검사가 용이해짐에 따라 불명열에 대한 접근 방법도 다소 변하고 있다. 저자들은 장기간의 원인 없는 열로 입원한 환아를 대상으로 그 원인과 검사 내용 및 결과를 조사하여 이런 환아들의 접근 방향에 도움을 얻고자 하였다. 방 법 : 1999년 7월부터 2004년 6월까지 5년 동안 부산대학교 병원에 입원하였던 환아들 중, $38^{\circ}C$ 이상의 발열이 외래에서 2주 이상 지속되거나 다른 병원에 입원해서 1주 이상 관찰되었던 환아가 본원 입원 당시에 그 진단이 확실하지 않았던 91명을 대상으로 하였다. 환아들의 의무기록지를 바탕으로 임상 소견, 각종 검사의 결과, 원인 질환 및 치료 결과를 조사하였다. 결 과 : 남아가 54명, 여아가 37명이었고 남녀비는 1.5:1이었다. 1세에서 6세 사이가 32예(35.0%)로 가장 많았고, 6세 미만이 약 반수를 차지하였으며, 평균 연령은 6.48세였다. 입원 전 발열 기간은 3주 이하가 62례(68.1%)였고 4주 이상 발열이 지속된 경우도 26례(28.6%)였다. 총 91명중 66명(72.5%)에서 진단할 수 있었다. 감염성 질환이 38례(41.7%)로 가장 많았고 교원성 질환이 12례(13.2%), 면역 결핍이 3례(3.3%), 악성 종양이 2례(2.2%)였으며 그 밖의 질환으로 괴사성 림프절염이 5례로 가장 많았으며 단일 감염 요인 중에선 결핵이 가장 많았다. 명확한 원인을 밝힐 수 없었던 예는 25례로서 27.5%였다. 치료 결과 77례(84.6%)는 호전되었고 10례(11.0%)는 호전되지 못한 채 퇴원하거나 전원하였으며 4명(4.4%)은 사망하였다. 결 론 : 불명열의 가장 흔한 원인은 감염성 질환이었으나 1970년대와 비교하여 그 비율은 감소하였고, 결핵은 단일 감염 요인 중 가장 높은 빈도를 보였다. 기타 질환 중에서 괴사성 림프절염의 빈도가 높아서 백혈구 감소가 있는 림프절 비대가 있을 때 고려해야 하겠다. 이전의 연구에 비해 진단되지 않는 비율은 27.5%로 증가하였다.

Keywords

References

  1. Pizzo PA, Lovejoy FH Jr, Smith DH. Prolonged fever in children: review of 100 cases. Pediatrics 1975;55:468-73
  2. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine 1961;40:1-30. https://doi.org/10.1097/00005792-196102000-00001
  3. Dummer S. The spectrum of FUOs in the '90s. Antimicrobics infectous Dis. Newsletter 1997;16:25-7 https://doi.org/10.1016/S1069-417X(00)80016-3
  4. Akpede GO, Akenzua GI. Management of children with prolonged fever of unknown origin and difficulties in the management of fever of unknown origin in children in developing countries. Paediatr Drugs 2001;3:247-62 https://doi.org/10.2165/00128072-200103040-00002
  5. Steele RW, Jones SM, Lowe BA, Glasier CM. Usefulness of scanning procedures for diagnosis of fever of unknown origin in children. J Pediatr 1991;119:526-30 https://doi.org/10.1016/S0022-3476(05)82399-6
  6. Knockaert DC, Vanneste LJ, Vanneste SB, Bobbaers HJ.Fever of unknown origin in the 1980s. An update of the diagnostic spectrum. Arch Intern Med 1992;152:51-5 https://doi.org/10.1001/archinte.152.1.51
  7. Han KS, Yun DJ. Prolonged fever in children : review of 120 cases. J Korean Pediatr Soc 1979;22:931-9
  8. Shin JH, Han JW, Lee SY, Lee WG, Moon SS, Park CM. Prolonged fever in infants and children. J Korean Pediatr Soc 1983;26:449-54
  9. Bourrillon A. Management of prolonged fever in infants. Arch Pediatr 1999;6:330-5 https://doi.org/10.1016/S0929-693X(99)80276-0
  10. Miller ML, Szer I, Yogev R, Bernstein B. Fever of unknown origin. Pediatr Clin North Am 1995;42:999-1015. https://doi.org/10.1016/S0031-3955(16)40050-7
  11. Chiang TM, Chang TY. Clinical observation and analysis of febrile children. Zhonghua Yi Xue Za Zhi(Taipei) 1993;51:431-5
  12. Ponce-de-Leon-Rosales S, Molina-Gamboa J, Rivera-Morales I. The changing spectrum of fever of unknown origin in Mexico. Clin Infect Dis 1994;19:353 https://doi.org/10.1093/clinids/19.2.353
  13. Cogulu O, Koturoglu G, Kurugol Z, Ozkinay F, Vardar F, Ozkinay C. Evaluation of 80 children with prolonged fever. Pediatr Int 2003;45:564-9 https://doi.org/10.1046/j.1442-200X.2003.01793.x
  14. De Kleijn EM, Vandenbroucke JP, van der Meer JW. Fever of unknown origin(FUO). I A. prospective multicenter study of 167 patients with FUO, using fixed epidemiologic entry criteria. The Netherlands FUO Study Group. Medicine 1997; 76:392-400 https://doi.org/10.1097/00005792-199711000-00002
  15. Drenth JP, de Kleijn EH, de Mulder PH, van der Meer JW. Metastatic breast cancer presenting as fever, rash, and arthritis. Cancer 1995;75:1608-11 https://doi.org/10.1002/1097-0142(19950401)75:7<1608::AID-CNCR2820750709>3.0.CO;2-A
  16. Scagni P, Peisino M, Bianchi M, Morello M, Sardi N, Linari A et al. Kikuchi-Fujimoto Disease Is a Rare Cause of Lymphadenopathy and Fever of Unknown Origin in Children: Report of Two Cases and Review of the Literature. J Pediatr Hematol Oncol. 2005;27:337-40 https://doi.org/10.1097/01.mph.0000169250.49988.7f
  17. McCarthy PL. Fever without apparent source on clinical examination. Curr Opin Pediatr. 2004;16:94-106 https://doi.org/10.1097/00008480-200402000-00018
  18. Arnow PM, Flaherty JP. Fever of unknown origin. Lancet. 1997;350:575-80 https://doi.org/10.1016/S0140-6736(97)07061-X
  19. Talano JA, Katz BZ. Long-term follow-up of children with fever of unknown origin. Clin Pediatr 2000;39:715-7 https://doi.org/10.1177/000992280003901205
  20. Miller LC, Sisson BA, Tucker LB, Schaller JG. Prolonged fevers of unknown origin in children: patterns of presentation and outcome. J Pediatr 1996;129:419-23 https://doi.org/10.1016/S0022-3476(96)70075-6