LI Zhi 1, QI Jun-ying 2*, GUO Wei 2, GUO Hui 2 1 Department of Infectious Diseases, 161 Hospital of PLA, Wuhan , China

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1 [ ](FUO) FUO FUO (86.8%) 150 (44.1%) 145 (42.7%)45 (13.2%) 186 (54.7%) 154 (45.3%) ( ) Still( ) (59.4%) (14.7%) >8 88 (25.9%) FUO [ ] [ ] R441.3 [ ] A [ ] (2013) LI Zhi 1, QI Jun-ying 2*, GUO Wei 2, GUO Hui 2 1 Department of Infectious Diseases, 161 Hospital of PLA, Wuhan , China 2 Department of Infectious Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, Wuhan , China *Corresponding author, jyqi@tjh.tjmu.edu.cn [Abstract] Objective To analyze the etiology, clinical characteristics and diagnostic methods of fever of unknown origin (FUO), so as to provide a reference for the diagnosis and treatment of FUE. Methods The clinical data of 340 patients with FUO admitted in Tongji Hospital from Jan to Dec were retrospectively analyzed. The relationship between etiology and gender, age of the patients, and course of fever were comprehensively evaluated, and the diversity of disease spectrum was also analyzed. Results Among the 340 patients analyzed, 295(86.76%) the diagnosis was definitely made. As to the etiology, 150(50.85%) were suffering from infectious diseases, 145(49.15%) non-infectious diseases, and in 45(13.24%) the etiology remained unknown till they were discharged from hospital. Among all of the patients, 186(54.71%) were male and 154(45.29%) were female. No significant difference existed in the ratio of disease distribution between male and female patients, but the incidence of connective tissue disease was significantly higher in female patients than in male patients, while the incidence of lymphoma was significantly higher in male patients than in females. As to the age distribution of the disease, 66 patients (19.41%) were younger than 20 years old, 98 patients (28.82%) were 21-40, 136(40.00%) were 41-60, and 40(11.76%) were older than 60. The mean age of patients suffering from solid tumors was the highest ( years), and that of adult Still disease was youngest ( years). The course of fever in 202 patients (59.41%) was shorter than 4 weeks, that of 50 patients (14.71%) was 4-8 weeks, and in 88 patients (25.88%) it was longer than 8 weeks. Febrile course was longest in patients suffering from connective tissue disease, lymphoma and tuberculosis. Conclusions Most of the patients with FUO could be definitely diagnosed prudent inquiry of history, followed by scrupulous physical examination, aided by appropriate instrumental examination, most cases of FUO could be definitely diagnosis. Among these patients, infectious diseases remain the main causes of FUO. The disease spectrum will be diverse due to different gender, age and course of fever. [Key words] fever of unknown origin; diagnosis; retrospective studies [ ] [ ] ( ) ( ) [ ] jyqi@tjh.tjmu.edu.cn

2 (fever of unknown origin FUO) FUO 340 FUO FUO : (13 80) Petersdorf Beeson [1] FUO [2] 1.3 Excel SAS 8.0 χ 2 FisherP< % %(11/14) 10 ( ) 3 [ (MRSA)1 1 1 ] 1 ( ) 11 ( 1) 1FUO Fig.1 Cause composition of FUO patients Infectious disease(n=150) Case Percentage(%) Non infectious disease(n=145) Case Percentage(%) Bacterial infection Connective tissue disease Typhoid fever Adult onset still's disease Tuberculosis Solid tumor Viruses Lymphoma Parasite Hyperthyroidism Fungus Drug fever Diseases of blood system (P>0.05) (P<0.05) (P<0.05 2) 2.3 Still ( ) Still FUO (59.4%) (14.7%) >8 88 (25.9%) ( d)> ( d)> ( d)> ( d)> Still ( d)> ( d) Still d ( d) ( d) % % (P>0.05) 2[ (%)] Fig.2 Comparison of disease spectrum between male and female patients [case(%)] Gender Infectious disease Connective tissue disease Adult onset Still's disease Diseases of blood system Solid tumor Lymphoma Male 81(52.3) 14(9.0) 8(5.2) 11(7.1) 11(7.1) 24(15.5) Female 69(57.0) 25(20.7) (1) 6(5.0) 14(11.6) 15(12.4) 10(8.3) (1) (1)P<0.05 compared with male

3 FUO [ (%)] Fig.3 Characteristics of main etiological distribution from 2005 to 2010[case(%)] Cause of disease Infectious disease 19(54.3) 17(60.7) 17(46.0) 29(56.9) 24(42.1) 37(47.4) Bacterial infection 11(31.4) 13(46.4) 11(29.7) 17(33.3) 13(22.8) 17(21.8) Tuberculosis 3(8.6) 3(10.7) 4(10.8) 7(13.7) 6(10.5) 12(15.4) Connective tissue disease 2(5.7) 2(7.1) 5(13.5) 5(9.8) 13(22.8) 12(15.4) Adult onset Still's disease 3(8.6) 1(3.6) 1(2.7) 3(5.9) 2(3.5) 4(5.1) Solid tumor 3(8.6) 1(3.6) 3(8.1) 4(7.8) 6(10.5) 9(11.5) Lymphoma 6(17.1) 3(10.7) 7(18.9) 5(9.8) 6(10.5) 7(9.0) Diseases of blood system 1(2.9) 3(10.7) 4(10.8) 4(7.8) 5(8.8) 8(10.3) Sum FUO [3] 340 FUO % [4-6] FUO 44.1% [6] 27.8% 11.9% ( Still ) (18.0%) (11.5%) (8.8%) (8.5%) %(11/14) 71.4%(10/14) FUO1~ % Still Still % Still Still [7-8] 4060 [7] Still 71 Still C (SFe) Still SFe5 StillSFe [9] Still 86.52% SFe % SFe (>10 ) Still 20% SFe [10] 35 60

4 FUO PPD [11] PPD PPD [12] 70.97% 3 4 [13] 5d 14d (T-cell interferon gamma release assays TIGRA) TIGRA PPD HIV % 1 13d 4d 1~2 FUO 8 4 [14] 67 Ga- - (FDG-PET) 18 F-FDG-PET ( ) FDG FDG [15] FDG-PET [16] FDG [17] SUV [18] 18 F-FDG (SU V max ) FUO FUO FUO [1] Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases[j]. Medicine, 1961, 40: [2] Bleeker-Rovers CP, Vos FJ, de Kleijn EM, et al. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol[j]. Medicine(Baltimore), 2007, 86(1): [3] Ni W, Miu XH, Zhang RQ, et al. Fever of unknown origin: a retrospective analysis of 107 clinical cases[j]. Med J Chin PLA, 2002, 27(10): [,,,. 107 [J]., 2002, 27(10): ] [4] Turkulov V, Brki S, Sevi S, et al. Fever of unknown origin in elderly patients[j]. Srp Arh Celok Lek, 2011, 139(1-2): [5] Moawad MA, Bassil H, Elsherif M, et al. Fever of unknown origin:98 cases from Saudi Arabia[J].Ann Saudi Med, 2010, 30(4): [6] Ma XJ, Wang AX, Deng GH, et al. A clinical review of 449 cases with fever of unknown origin[j]. Chin J Intern Med, 2004, 43(9): [,,,. 449 [J]., 2004, 43(9): ] [7] Chen J, Li FJ, Chen M, et al. Retrospective analysis of adult onset still's disease[j]. J Luzhou Med Coll, 2009, 32(2): [,,,. Still[J]., 2009, 32(2): ] [8] Tao ZW. The discussion of adult Still diseases diagnosis and treatment[j]. Chin J Pract Intern Med, 2009, 29(12): [. Still [J]., 2009, 29(12): ] [9] Fautrel B. Ferritin levels in adult Still's disease:any sugar[j]? Joint Bone Spine, 2002, 69(4): [10] Vignes S, Le Moël G, Fautrel B, et al. Percentage of glycosylated serum ferritin remains low throughout the course of adult onset Still's disease[j]. Ann Rheum Dis, 2000, 59(5):

5 [11] Shi XP, Qimanguli Wushouer, Wang Q, et al. Significance of serum neopterin level in diagnosis of active pulmonary tuberculosis[j]. Med J Chin PLA, 2011, 36(10): [,,,. [J]., 2011, 36(10): ] [12] Tu DH. Application of tuberculin test[j]. Buccetin Chin Antituberculosis Association, 2001,23(2): [. [J]., 2001, 23(2): ] [13] Wong XH, Chen S. The pathogenic diagnosis and rational treatment of fever of unknown origin[j]. Chin J Intern Med, 2003, 42(4): [,. [J]., 2003, 42(4): ] [14] Zhou YJ, Deng ZY, Sun H, et al. Patients with lung cancer 99mTc-MDP bone scan time of review[j]. Chin J Pract Intern Med, 2011, 31(3): [,,,. 99mTc-MDP[J]., 2011, 31(3): ] [15] Zhuang H, Alavi A. 18-fluorodeoxyglucose positron emission tomography imaging in the detection and monitoring of infection and inflammation[j]. Semin Nucl Med, 2002, 32(1): [16] Bleeker-Rovers CP, Boerman OC, Rennen HJ, et al. Radiolabeled compounds in diagnosis of infectious and inflammatory disease[j]. Curr Pharm Des, 2004, 10(24): [17] Zhang SW, Tian JH, He YJ, et al. Clinical value of (18) FDG- PET for patients with fever of unknown origin[j]. Chin J Med Imaging, 2003, 11(2): [,,,. 18F-FDG-PET [J]., 2003, 11(2): ] [18] Zhang BQ, Zhang YX, Wu T, et al. Diagnostic value of (18) F-FDG PET/CT in defining the etiology of fever of unknown origin[j]. Radiol Pract, 2010, 25(6): [,,,. 18F-FDG PET/CT [J]., 2010, 25(6): ] ( ) ( )

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