성인 혈구탐식증후군 환자들의 원인과 사망에 관련된 요인 = Causes and Risk Factors of Mortality in Adult Patients with Hemophagocytic Syndrome

다국어 초록 (Multilingual Abstract)

Background: Hemophagocytic syndrome (HS) is a distinct clinical entity characterized by high fever and hemophagocytosis with histiocytosis in tissue biopsy. We seldom encounter patients who suffer from unexplained, persistent fevers. Although there have been many studies about childhood HS, studies about adult HS are relatively rare. The causes and prognoses of HS in adults were evaluated in this study. We focused on infection-related HS.
Material and Methods: We enrolled 41 adult patients with HS retrospectively from four hospitals in Kyungbuk province and Daegu city. The patients were diagnosed by bone marrow or liver biopsy, either of which showed hemophagocytosis with histiocytosis and had clinical findings consistent with HS. We explored the etiologies,clinical symptoms, laboratory findings, treatments, and outcomes of each case.
Results: The most common cause of HS was infection, such as the Epstein-Barr virus (EBV) or Mycobacterium tuberculosis . Old age and malignancy-associated HS had a poor prognosis. The overall mortality rate was 17.1%. Most patients survived after conservative therapy and the control of underlying diseases, in contrast to previous studies that showed a poor prognosis of infection-associated HS.
Conclusions: A proper investigation is crucial to determine the cause of HS in patients who have unexplained persistent fever and hemophagocytosis with histiocytosis in their tissue. Cases of infection-related HS are common, but physicians should consider undiagnosed malignancy that may be related to a poor prognosis.
Treatments appropriate to the causes are important for better outcomes in adult HS.

참고문헌 (Reference)

1 오준혁, "혈구포식 림프조직구증을 동반한 Kikuchi병 1례" 대한감염학회 36 (36): 185-188, 2004

2 김형욱, "쯔쯔가무시병과 동반된 혈구탐식 림프조직구증으로 사망한 1예" 대한감염학회 42 (42): 266-270, 2010

3 Lee GR., "Wintrobe's clinical hematology. 9th ed" Lea & Febiger 2189-2191, 1993

4 Risdall RJ., "Virus-associated hemophagocytic syndrome : a benign histiocytic proliferation distinct from malignant histiocytosis" 44 : 993-1002, 1979

5 정지인, "Virus-associated hemophagocytic syndrome 1예" 대한내과학회 75 (75): 322-326, 2008

6 Ryu DR., "Two cases of infectionassociated hemophagocytic syndrome with review of literature" 30 : 470-477, 1998

7 Chandra P., "Transient histiocytosis with striking phagocytosis of platelets, leukocytes, and erythrocytes" 135 : 989-991, 1975

8 Yoon HJ., "Successful treatment with intravenous immunoglobulin and etoposide in a systemic lupus erythematosus patient with hemophagocytic syndrome" 70 : S363-S367, 2006

9 Shukla N., "Successful treatment of refractory metastatic histiocytic sarcoma with alemtuzumab" 2011

10 Dhote R., "Reactive hemophagocytic syndrome in adult systemic disease : report of twenty-six cases and literature review" 49 : 633-639, 2003

11 Kim IH., "Reactive hemophagocytic syndrome : a clinical study of 16 cases" 30 : 397-405, 1995

12 Levy L., "Prolonged fever, hepatosplenomegaly, and pancytopenia in a 46-year-old woman" 6 : e1000053-, 2009

13 Larroche C., "Pathogenesis of hemophagocytic syndrome(HPS)" 3 : 69-75, 2004

14 Ishii E., "Nationwide survey of hemophagocytic lymphohistiocytosis in Japan" 86 : 58-65, 2007

15 Schmidt D., "Malignant histiocytosis" 8 : 1-4, 2001

16 Fardet L., "Low glycosylated ferritin, a good marker for the diagnosis of hemophagocytic syndrome" 58 : 1521-1527, 2008

17 Janka G., "Infection-and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis" 12 : 435-444, 1998

18 Chen RL., "Immunomodulation treatment for childhood virus-associated haemophagocytic lymphohistiocytosis" 89 : 282-290, 1995

19 Esumi N., "High serum ferritin level as a marker of malignant histiocytosis and virusassociated hemophagocytic syndrome" 61 : 2071-2076, 1988

20 Fisman DN., "Hemophagocytic syndromes and infection" 6 : 601-608, 2000

21 Lee SY., "Hemophagocytic histiocytosis : analysis of underlying causes and hematological findings" 16 : 435-446, 1996

22 Cunha BA., "Fever of unknown origin : focused diagnostic approach based on clinical clues from the history, physical examination, and laboratory tests" 21 : 1137-1187, 2007

23 Cunha BA., "Fever of unknown origin : clinical overview of classic and current concepts" 21 : 867-915, 2007

24 Zhiyong Z., "Fever of unknown origin : a report from China of 208 cases" 57 : 592-596, 2003

25 Petersdorf RG., "Fever of unexplained origin : report on 100 cases" 40 : 1-30, 1961

26 Kim JW., "Epstein-Barr virusassociated hemophagocytic syndrome confirmed by in situ hybridization : case report and review of the related literature" 16 : 369-375, 1998

27 Albrecht H., "Epstein-Barr virus--Associated hemophagocytic syndrome. A cause of fever of unknown origin in human immunodeficiency virus infection" 121 : 853-858, 1997

28 Han B., "Diagnostic splenectomy in patients with fever of unknown origin and splenomegaly" 119 : 83-88, 2008

29 Henter JI., "Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society" 18 : 29-33, 1991

30 Risdall RJ., "Bacteriaassociated hemophagocytic syndrome" 54 : 2968-2972, 1984

31 Mourad O., "A comprehensive evidencebased approach to fever of unknown origin" 163 : 545-551, 2003

32 Kim YK., "A comparison of causes of fever of unknown origin between the 1980s and the 1990s" 61 : 546-552, 2001

33 Oh MD., "A clinical study on 55 patients with fever of undetermined origin" 25 : 1-8, 1993

34 Su NW., "A case of tuberculosis-induced hemophagocytic lymphohistiocytosis in a patient under hemodialysis" 89 : 298-301, 2009

35 Ryoo HO., "A case of infectionassociated hemophagocytic syndrome(IAHS)" 25 : 71-77, 1993

36 Kang SK., "A case of infection-associated hemophagocytic syndrome associated with CMV mononucleosis" 25 : 387-391, 1993

37 Yang CW., "A case of Rickettsia-associated pancytopenia and hemophagocytosis" 24 : 215-220, 1992

38 기세윤, "1998년부터 2003년까지 일개 대학 병원에서 관찰된 성인 불명열 환자의 원인" 대한감염학회 37 (37): 127-132, 2005