Evaluation of fever of unknown origin in adults

References

Key articles

Haidar G, Singh N. Fever of unknown origin. N Engl J Med. 2022 Feb 3;386(5):463-77. Abstract

Cunha BA, Lortholary O, Cunha CB. Fever of unknown origin: a clinical approach. Am J Med. 2015 Oct;128(10):1138.e1-1138.e15.Full text  Abstract

Wright WF, Auwaerter PG. Fever and fever of unknown origin: review, recent advances, and lingering dogma. Open Forum Infect Dis. 2020 May;7(5):ofaa132.Full text  Abstract

Reference articles

1. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961 Feb;40:1-30. Abstract

2. Durack DT, Street AC. Fever of unknown origin - reexamined and redefined. Curr Clin Top Infect Dis. 1991;11:35-51. Abstract

3. 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. Medicine (Baltimore). 1997 Nov;76(6):392-400. Abstract

4. Wright WF, Mulders-Manders CM, Auwaerter PG, et al. Fever of unknown origin (FUO) - a call for new research standards and updated clinical management. Am J Med. 2022 Feb;135(2):173-8. Abstract

5. Haidar G, Singh N. Fever of unknown origin. N Engl J Med. 2022 Feb 3;386(5):463-77. Abstract

6. Wright WF, Yenokyan G, Simner PJ, et al. Geographic variation of infectious disease diagnoses among patients with fever of unknown origin: a systematic review and meta-analysis. Open Forum Infect Dis. 2022 May;9(5):ofac151.Full text  Abstract

7. Fusco FM, Pisapia R, Nardiello S, et al. Fever of unknown origin (FUO): which are the factors influencing the final diagnosis? A 2005-2015 systematic review. BMC Infect Dis. 2019 Jul 22;19(1):653.Full text  Abstract

8. Gaeta GB, Fusco FM, Nardiello S. Fever of unknown origin: a systematic review of the literature for 1995-2004. Nucl Med Commun. 2006 Mar;27(3):205-11. Abstract

9. Wright WF, Wang J, Auwaerter PG. Investigator-determined categories for fever of unknown origin (FUO) compared with international classification of diseases-10 classification of illness: a systematic review and meta-analysis with a proposal for revised FUO classification. Open Forum Infect Dis. 2023 Mar;10(3):ofad104.Full text  Abstract

10. Mulders-Manders CM, Pietersz G, Simon A, et al. Referral of patients with fever of unknown origin to an expertise center has high diagnostic and therapeutic value. QJM. 2017 Dec 1;110(12):793-801.Full text  Abstract

11. Naito T, Tanei M, Ikeda N, et al. Key diagnostic characteristics of fever of unknown origin in Japanese patients: a prospective multicentre study. BMJ Open. 2019 Nov 19;9(11):e032059.Full text  Abstract

12. Wright WF, Yenokyan G, Auwaerter PG. Geographic influence upon noninfectious diseases accounting for fever of unknown origin: a systematic review and meta-analysis. Open Forum Infect Dis. 2022 Aug;9(8):ofac396.Full text  Abstract

13. Betrains A, Moreel L, De Langhe E, et al. Rheumatic disorders among patients with fever of unknown origin: A systematic review and meta-analysis. Semin Arthritis Rheum. 2022 Oct;56:152066. Abstract

14. Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol. 2017 Aug;31(4):596-609. Abstract

15. Delplanque M, Fayand A, Boursier G, et al. Diagnostic and therapeutic algorithms for monogenic autoinflammatory diseases presenting with recurrent fevers among adults. Rheumatology (Oxford). 2023 Aug 1;62(8):2665-72. Abstract

16. Watanabe R, Sakuraba H, Hiraga H, et al. Diagnostic approach for patients with unidentified fever according to the classical criteria of fever of unknown origin in the field of autoimmune disorders. Immunol Med. 2019 Dec;42(4):176-84.Full text  Abstract

17. Cantarini L, Vitale A, Sicignano LL, et al. Diagnostic criteria for adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Front Immunol. 2017;8:1018.Full text  Abstract

18. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93.Full text  Abstract

19. Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021 Aug;73(8):1349-65.Full text  Abstract

20. Cunha BA, Lortholary O, Cunha CB. Fever of unknown origin: a clinical approach. Am J Med. 2015 Oct;128(10):1138.e1-1138.e15.Full text  Abstract

21. National Institute for Health and Care Excellence. Headaches in over 12s: diagnosis and management. Dec 2021 [internet publication].​Full text

22. Czihal M, Lottspeich C, Bernau C, et al. A diagnostic algorithm based on a simple clinical prediction rule for the diagnosis of cranial giant cell arteritis. J Clin Med. 2021 Mar 10;10(6):1163.Full text  Abstract

23. Andel PM, Chrysidis S, Geiger J, et al. Diagnosing giant cell arteritis: a comprehensive practical guide for the practicing rheumatologist. Rheumatology (Oxford). 2021 Nov 3;60(11):4958-71.Full text  Abstract

24. Wright WF, Auwaerter PG. Fever and fever of unknown origin: review, recent advances, and lingering dogma. Open Forum Infect Dis. 2020 May;7(5):ofaa132.Full text  Abstract

25. Mackie SL, Dejaco C, Appenzeller S, et al. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis. Rheumatology (Oxford). 2020 Mar 1;59(3):e1-23.Full text  Abstract

26. Hellmich B, Agueda A, Monti S, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020 Jan;79(1):19-30.Full text  Abstract

27. Wright WF, Simner PJ, Carroll KC, et al. Progress report: next-generation sequencing, multiplex polymerase chain reaction, and broad-range molecular assays as diagnostic tools for fever of unknown origin investigations in adults. Clin Infect Dis. 2022 Mar 9;74(5):924-32.Full text  Abstract

28. Wright WF, Auwaerter PG, Dibble EH, et al. Imaging a fever-redefining the role of 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography/computed tomography in fever of unknown origin investigations. Clin Infect Dis. 2021 Apr 8;72(7):1279-86.Full text  Abstract

29. Iikuni Y, Okada J, Kondo H, et al. Current fever of unknown origin 1982-1992. Intern Med. 1994 Feb;33(2):67-73.Full text  Abstract

30. Mansueto P, Di Lorenzo G, Rizzo M, et al. Fever of unknown origin in a Mediterranean survey from a division of internal medicine: report of 91 cases during a 12-year-period (1991-2002). Intern Emerg Med. 2008 Sep;3(3):219-25. Abstract

31. Bleeker-Rovers CP, Vos FJ, de Kleijn EMHA, et al. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore). 2007 Jan;86(1):26-38.Full text  Abstract

32. Varghese GM, Trowbridge P, Doherty T. Investigating and managing pyrexia of unknown origin in adults. BMJ. 2010;341:C5470. Abstract

33. de Kleijn, Elisabeth M.H.A et al. Fever of unknown origin: a new definition and proposal for diagnostic work-up. Eur J Intern Med. 2000 Feb;11(1):1-3.

34. Mourad O, Palda V, Detsky AS. A comprehensive evidence-based approach to fever of unknown origin. Arch Intern Med. 2003 Mar 10;163(5):545-51.Full text  Abstract

35. Wright WF, Betz JF, Auwaerter PG. Prospective studies comparing structured vs nonstructured diagnostic protocol evaluations among patients with fever of unknown origin: a systematic review and meta-analysis. JAMA Netw Open. 2022 Jun 1;5(6):e2215000.Full text  Abstract

36. Knockaert DC. Recurrent fevers of unknown origin. Infect Dis Clin North Am. 2007 Dec;21(4):1189-211, xi. Abstract

37. Cunha BA. Fever of unknown origin: focused diagnostic approach based on clinical clues from the history, physical examination, and laboratory tests. Infect Dis Clin North Am. 2007 Dec;21(4):1137-87, xi. Abstract

38. Wagner AD, Andresen J, Raum E, et al. Standardised work-up programme for fever of unknown origin and contribution of magnetic resonance imaging for the diagnosis of hidden systemic vasculitis. Ann Rheum Dis. 2005 Jan;64(1):105-10.Full text  Abstract

39. Takeuchi M, Dahabreh IJ, Nihashi T, et al. Nuclear imaging for classic fever of unknown origin: meta-analysis. J Nucl Med. 2016 Dec;57(12):1913-9.Full text  Abstract

40. Bharucha T, Rutherford A, Skeoch S, et al. Diagnostic yield of FDG-PET/CT in fever of unknown origin: a systematic review, meta-analysis, and Delphi exercise. Clin Radiol. 2017 Sep;72(9):764-71. Abstract

41. Takeuchi M, Nihashi T, Gafter-Gvili A, et al. Association of 18F-FDG PET or PET/CT results with spontaneous remission in classic fever of unknown origin: a systematic review and meta-analysis. Medicine (Baltimore). 2018 Oct;97(43):e12909.Full text  Abstract

42. Dong MJ, Zhao K, Liu ZF, et al. A meta-analysis of the value of fluorodeoxyglucose-PET/PET-CT in the evaluation of fever of unknown origin. Eur J Radiol. 2011 Dec;80(3):834-44. Abstract

43. Kan Y, Wang W, Liu J, et al. Contribution of 18F-FDG PET/CT in a case-mix of fever of unknown origin and inflammation of unknown origin: a meta-analysis. Acta Radiol. 2019 Jun;60(6):716-25. Abstract

44. Dibble EH, Yoo DC, Baird GL, et al. FDG PET/CT of infection: should it replace labeled leukocyte scintigraphy of inpatients? AJR Am J Roentgenol. 2019 Dec;213(6):1358-65.Full text  Abstract

45. Mahajna H, Vaknin K, Ben Shimol J, et al. The utility of 18FDG-PET/CT in diagnosing fever of unknown origin: the experience of a large tertiary medical center. Int J Environ Res Public Health. 2021 May 18;18(10):5360.Full text  Abstract

46. Letertre S, Fesler P, Zerkowski L, et al. Place of the (18)F-FDG-PET/CT in the diagnostic workup in patients with classical fever of unknown origin (FUO). J Clin Med. 2021 Aug 26;10(17):3831.Full text  Abstract

47. Hayakawa K, Ramasamy B, Chandrasekar PH. Fever of unknown origin: an evidence-based review. Am J Med Sci. 2012 Oct;344(4):307-16. Abstract

48. Becerra Nakayo EM, García Vicente AM, Soriano Castrejón AM, et al. Analysis of cost-effectiveness in the diagnosis of fever of unknown origin and the role of (18)F-FDG PET-CT: a proposal of diagnostic algorithm [in Spanish]. Rev Esp Med Nucl Imagen Mol. 2012 Jul-Aug;31(4):178-86. Abstract

49. Chen J, Wang Q. Cost-effectiveness analysis of 18F-FDG PET/CT in the diagnosis of fever of unknown origin in China.​ J Nucl Med. 2019 May 1;60(1):1063.

50. van Rijsewijk ND, IJpma FFA, Wouthuyzen-Bakker M, et al. Molecular imaging of fever of unknown origin: an update. Semin Nucl Med. 2023 Jan;53(1):4-17.Full text  Abstract

51. Palestro C, Clark A, Grady E, et al. Appropriate use criteria for the use of nuclear medicine in musculoskeletal infection imaging. J Nucl Med. 2021 Sep 30;62(12):1815-31.Full text  Abstract

52. Hot A, Jaisson I, Girard C, et al. Yield of bone marrow examination in diagnosing the source of fever of unknown origin. Arch Intern Med. 2009 Nov 23;169(21):2018-23.Full text  Abstract

53. Fu ZF, Zhang HC, Zhang Y, et al. Evaluations of clinical utilization of metagenomic next-generation sequencing in adults with fever of unknown origin. Front Cell Infect Microbiol. 2021;11:745156.Full text  Abstract

54. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-5.Full text  Abstract

55. Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph node tuberculosis in northern Germany: a clinical review. Chest. 2002 Apr;121(4):1177-82. Abstract

56. Weir MR, Thornton GF. Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med. 1985 Oct;79(4):467-78. Abstract

57. Baydur A. The spectrum of extrapulmonary tuberculosis. West J Med. 1977 Apr;126(4):253-62. Abstract

58. Nataraj G, Kurup S, Pandit A, et al. Correlation of fine needle aspiration cytology, smear and culture in tuberculous lymphadenitis: a prospective study. J Postgrad Med. 2002 Apr-Jun;48(2):113-6. Abstract

59. Centers for Disease Control and Prevention. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. Jan 2009 [internet publication].Full text

60. World Health Organization. WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication].​Full text

61. Bjerrum S, Schiller I, Dendukuri N, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019 Oct 21;10(10):CD011420.Full text  Abstract

62. Centers for Disease Control and Prevention. 2018 quick reference guide: recommended laboratory HIV testing algorithm for serum or plasma specimens. January 2018 [internet publication].Full text

63. Centers for Disease Control and Prevention. Laboratory testing for the diagnosis of HIV infection: updated recommendations. June 2014 [internet publication].Full text

64. McCormack J, Pollard J. Aspergillus endocarditis 2003-2009. Med Mycol. 2011 Apr;49 Suppl 1:S30-4.Full text  Abstract

65. Talha KM, DeSimone DC, Sohail MR, et al. Pathogen influence on epidemiology, diagnostic evaluation and management of infective endocarditis. Heart. 2020 Dec;106(24):1878-82. Abstract

66. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med. 1994 Mar;96(3):200-9. Abstract

67. Kupferwasser LI, Darius H, Muller AM, et al. Diagnosis of culture-negative endocarditis: the role of the Duke criteria and the impact of transesophageal echocardiography. Am Heart J. 2001 Jul;142(1):146-52. Abstract

68. Centers for Disease Control and Prevention (CDC). Recommendations for test performance and interpretation from the second national conference on serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 1995 Aug 11;44(31):590-1. Abstract

69. Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):703.Full text  Abstract

70. Knockaert DC, Vanneste LJ, Bobbaers HJ. Recurrent or episodic fever of unknown origin. Review of 45 cases and survey of the literature. Medicine (Baltimore). 1993 May;72(3):184-96. Abstract

71. Salvarani C, Cantini F, Boiardi L, et al. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med. 2002 Jul 25;347(4):261-71. Abstract

72. Dejaco C, Ramiro S, Bond M, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update. Ann Rheum Dis. 2023 Aug 7;ard-2023-224543.Full text  Abstract

73. Ponte C, Grayson PC, Robson JC, et al. 2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis. Arthritis Rheumatol. 2022 Dec;74(12):1881-9. Abstract

74. Younge BR, Cook BE Jr, Bartley GB, et al. Initiation of glucocorticoid therapy: before or after temporal artery biopsy? Mayo Clin Proc. 2004 Apr;79(4):483-91. Abstract

75. Saraux A, Berthelot JM, Chales G, et al. Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. Arthritis Rheum. 2001 Nov;44(11):2485-91. Abstract

76. Sieper J, Rudwaleit M, Braun J, et al. Diagnosing reactive arthritis: role of clinical setting in the value of serologic and microbiologic assays. Arthritis Rheum. 2002 Feb;46(2):319-27.Full text  Abstract

77. van der Linden SM, Valkenburg HA, de Jongh BM, et al. The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum. 1984 Mar;27(3):241-9.Full text  Abstract

78. Omair MA, AlDuraibi FK, Bedaiwi MK, et al. Prevalence of HLA-B27 in the general population and in patients with axial spondyloarthritis in Saudi Arabia. Clin Rheumatol. 2017 Jul;36(7):1537-43. Abstract

79. Arnow PM, Flaherty JP. Fever of unknown origin. Lancet. 1997 Aug 23;350(9077):575-80. Abstract

80. Thillai M, Atkins CP, Crawshaw A, et al. BTS Clinical Statement on pulmonary sarcoidosis. Thorax. 2021 Jan;76(1):4-20. Abstract

81. World Health Organization. WHO guidelines for malaria. 2023 [internet publication].​Full text

82. Rogers CL, Bain BJ, Garg M, et al. British Society for Haematology guidelines for the laboratory diagnosis of malaria. Br J Haematol. 2022 May;197(3):271-82.Full text  Abstract

83. Pattanasin S, Proux S, Chompasuk D, et al. Evaluation of a new Plasmodium lactate dehydrogenase assay (OptiMAL-IT) for the detection of malaria. Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):672-4. Abstract

84. Ashley EA, Touabi M, Ahrer M, et al. Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria. Malar J. 2009 Oct 27;8:241.Full text  Abstract

85. Yerlikaya S, Campillo A, Gonzalez IJ. A Systematic review: performance of rapid diagnostic tests for the detection of Plasmodium knowlesi, Plasmodium malariae, and Plasmodium ovale monoinfections in human blood. J Infect Dis. 2018 Jun 20;218(2):265-76.Full text  Abstract

86. Stauffer WM, Cartwright CP, Olson DA, et al. Diagnostic performance of rapid diagnostic tests versus blood smears for malaria in US clinical practice. Clin Infect Dis. 2009 Sep 15;49(6):908-13.Full text  Abstract

87. Nicastri E, Bevilacqua N, Sañé Schepisi M, et al. Accuracy of malaria diagnosis by microscopy, rapid diagnostic test, and PCR methods and evidence of antimalarial overprescription in non-severe febrile patients in two Tanzanian hospitals. Am J Trop Med Hyg. 2009 May;80(5):712-7. Abstract

88. World Health Organization, Regional Office for South-East Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever - revised and expanded edition. 2011 [internet publication].Full text

89. Teixeira MG, Barreto ML. Diagnosis and management of dengue. BMJ. 2009 Nov 18;339:b4338. Abstract

90. Centers for Disease Control and Prevention. CDC DENV-1-4 real-time RT-PCR multiplex assay. Jun 2023 [internet publication].Full text

91. Centers for Disease Control and Prevention. CDC DENV-1-4 rRT-PCR multiplex and trioplex rRT-PCR assays. Jan 2020 [internet publication].​Full text

92. Lima Mda R, Nogueira RM, Schatzmayr HG, et al. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis. 2010 Jul 6;4(7):e738.Full text  Abstract

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