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Fever of unknown origin


Authors: Vyacheslav Grebenyuk 1,2;  Olga Kryštůfková 3;  Monika Gregová 3;  Magdalena Sokalská-Jurkiewicz 3;  Renata Steinbauerová 4;  Marie Sukovská 4;  Lubica Gahérová 5;  Ivana Zubatá 5;  Jana Gregorová 6;  Lucia Kaliská 7;  Hana Roháčová 2;  Milan Trojánek 1,2,8
Authors‘ workplace: Klinika infekčních nemocí, 2. lékařská fakulta, Univerzita Karlova, Praha 1;  Klinika infekčních, parazitárních a tropických nemocí, Fakultní nemocnice Bulovka, Praha 2;  Revmatologický ústav, Praha 3;  Oddělení klinické hematologie, Fakultní nemocnice Bulovka, Praha 4;  Interní hematologická klinika, 3. lékařská fakulta a Fakultní nemocnice Královské Vinohrady, Praha 5;  Oddělení klinické farmacie, Praha 6;  Oddělení nukleární medicíny, Proton Therapy Center Czech, Praha 7;  Katedra infekčního lékařství, IPVZ, Praha 8
Published in: Vnitř Lék 2021; 67(1): 32-42
Category: Differential Diagnosis Column or What You Can Be Asked at a Postgraduate Certification Exam

Overview

Fever of unknown origin is a rare clinical syndrome, that represents a significant diagnostic challenge. There have been described more than 200 potential diseases, that can manifest as a fever of unknown origin. These are classically divided into following categories: infections, non-infectious inflammatory diseases, malignancies, and other miscellaneous disorders. Each of the disease type is associated with rather characteristic symptoms, clinical signs and laboratory findings, which are individually non-specific, but may provide helpful clues for a further focused diagnostic work-up. The clinician’s task is to be able to identify these hallmark clinical features and to correctly interpret their significance and limitations in the appropriate differential diagnostic context. The aim of this review is to provide up-to-date clinical research evidence and to propose a  concise clue-oriented diagnostic approach.

Keywords:

diagnostic imaging – differential diagnosis – fever – granulomatous diseases – infections – inflammation – medical history taking – neoplasms – physical examination – rheumatic diseases


Sources

1. Vanderschueren S, Knockaert D, Adriaenssens T, et al. From prolonged febrile illness to fever of unknown origin: the challenge continues. Arch Intern Med 2003; 163(9): 1033–1041.

2. Arnow PM, Flaherty JP. Fever of unknown origin. Lancet 1997; 350(9077): 575–580.

3. 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. Medicine (Baltimore) 2007; 86(1): 26–38.

4. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore) 1961; 40: 1–0.

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

6. Knockaert DC, Vanneste LJ, Vanneste SB, et al. Fever of Unknown Origin in the 1980 s: An Update of the Diagnostic Spectrum. Arch Intern Med 1992; 152(1): 51–55.

7. Hayakawa K, Ramasamy B, Chandrasekar PH. Fever of unknown origin: an evidence-based review. Am J Med Sci 2012; 344(4): 307–316.

8. 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 (Baltimore) 1997; 76(6): 392–400.

9. Mourad O, Palda V, Detsky AS. A comprehensive evidence -based approach to fever of unknown origin. Arch Intern Med 2003; 163(5): 545–551.

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

11. Bleeker -Rovers CP, van der Meer JWM. Fever of unknown origin. In: Kasper DL, Fauci AS, Longo DL, Hauser SL, Jameson JL, Loscalzo J (eds). Harrison’s Principles of Internal Medicine. 19th ed. McGraw -Hill: New York 2016: 135–142.

12. Hersch EC, Oh RC. Prolonged febrile illness and fever of unknown origin in adults. Am Fam Physician 2014; 90(2): 91–96.

13. Kouijzer IJE, Mulders -Manders CM, Bleeker -Rovers CP, et al. Fever of Unknown Origin: the Value of FDG -PET/CT. Semin Nucl Med 2018; 48(2): 100–107.

14. Mackowiak PA, Durack DT. Fever of unknown origin. In: Bennett JE, Dolin R, Blaser MJ, Parta M (eds). Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Elsevier Saunders: Philadelphia 2015: 721–729.

15. Bottieau E, Clerinx J, Van den Enden E, et al. Fever after a stay in the tropics: diagnostic predictors of the leading tropical conditions. Medicine (Baltimore) 2007; 86(1): 18–25.

16. Zenone T. Fever of unknown origin in rheumatic diseases. Infect Dis Clin North Am 2007; 21(4): 1115–1135.

17. Gerfaud -Valentin M, Jamilloux Y, Iwaz J, Sève P. Adult -onset Still’s disease. Autoimmun Rev 2014; 13(7): 708–722.

18. Foggo V, Cavenagh J. Malignant causes of fever of unknown origin. Clin Med (Lond) 2015; 15(3): 292–294.

19. Chang JC, Gross HM. Utility of naproxen in the differential diagnosis of fever of undetermined origin in patients with cancer. Am J Med 1984; 76: 597–603.

20. Roush MK, Nelson KM. Understanding drug -induced febrile reactions. Am Pharm 1993; 33(10): 39–42.

21. Mackowiak PA. Drug fever: mechanisms, maxims and misconceptions. Am J Med Sci. 1987; 294(4): 275–286.

22. Ochi H, Wada K, Okada H, et al. The persistence of drug -induced fever by teicoplanin-a case report. Int J Clin Pharmacol Ther. 2011; 49(5): 339–343.

23. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994; 331(19): 1272–1285.

24. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: Part I. Clinical perspectives. J Am Acad Dermatol 2013; 68(5): 693.e1–e14.

25. 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; 21(4): 1137–1187.

26. Kovačevičová M, Švestková S. Retikulární exantémy – patofyziologie, etiopatogeneze, klasifikace. Čes -slov Derm 2012; 87(6): 211–219.

27. Fogo A, du Vivier A. The cutaneous manifestations of haematological malignancy. Clin Med (Lond) 2009; 9(4): 366–370.

28. Shmerling RH. Evaluation of the adult with polyarticular pain. UpToDate 2020. [cit. 2020-06-25]. Dostupné z www: .

29. Gaddey HL, Riegel AM. Unexplained Lymphadenopathy: Evaluation and Differential Diagnosis. Am Fam Physician 2016; 94(11): 896–903.

30. Bona R. Evaluation of splenomegaly and other splenic disorders in adults. UpToDate 2020. [cit. 2020-06-25]. Dostupné z www: .

31. Curry MP, Bonder A. Overwiew of the evaluation of hepatomegaly in adults. UpToDate. 2020 [cited 2020 Jun 25]. Dostupné z www: .

32. Loughrey PB, Armstrong D, Lockhart CJ. Classical eye signs in bacterial endocarditis. QJM 2015; 108(11): 909–910.

33. Ruddy SM, Bergstrom R, Tivakaran VS. Roth Spots. StatPearls 2020. [cit. 2020-06-25]. Dostupné z www: .

34. Shane E. Diagnostic approach to hypercalcemia. UpToDate 2020. [cit. 2020-07-12]. Dostupné z www: < https://www.uptodate.com/contents/diagnostic -approach -to -hypercalcemia>.

35. Bray C, Bell LN, Liang H, et al. Erythrocyte Sedimentation Rate and C -reactive Protein Measurements and Their Relevance in Clinical Medicine. WMJ 2016; 115(6): 317–321.

36. Simon L, Gauvin F, Amre DK, et al. Serum procalcitonin and C -reactive protein levels as markers of bacterial infection: a systematic review and meta -analysis. Clin Infect Dis 2004; 39(2): 206–217.

37. Maruna P. Proteiny akutní fáze. 1. vydání. Maxdorf: Praha 2004.

38. Erez A, Shental O, Tchebiner JZ, et al. Diagnostic and prognostic value of very high serum lactate dehydrogenase in admitted medical patients. Isr Med Assoc J 2014; 16(7): 439–443.

39. Li L, Dong M, Wang XG. The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator. Chin Med J (Engl) 2016; 129(4): 448–455.

40. Castro C, Gourley M. Diagnostic testing and interpretation of tests for autoimmunity. J Allergy Clin Immunol 2010; 125(Suppl 2): S238–S247.

41. Dasgupta A, Wahed A. Protein Electrophoresis and Immunofixation. In Dasgupta A, Wahed A (authors). Clinical chemistry, immunology and laboratory quality control: A comprehensive review for board preparation, certification and clinical practice. 1st ed. Elsevier: Amsterdam 2014: 391–405.

42. Casulo C, Maragulia J, Zelenetz AD. Incidence of Hypogammaglobulinemia in Patients Receiving Rituximab and the Use of Intravenous Immunoglobulin for Recurrent Infections. Clin Lymphoma Myeloma Leuk 2013; 13(2): 106–111.

43. De Angelis F, Tosti ME, Capria S, et al. Risk of secondary hypogammaglobulinaemia after Rituximab and Fludarabine in indolent non -Hodgkin lymphomas: A retrospective cohort study. Leuk Res 2015; 39(12): 1382–1388.

44. Guyomard S, Salles G, Coudurier M et al. Prevalence and pattern of antinuclear autoantibodies in 347 patients with non-Hodgkin’s lymphoma. Br J Haematol 2003; 123(1): 90–99.

45. Coburn B, Morris AM, Tomlinson G, et al. Does this adult patient with suspected bacteremia require blood cultures? JAMA 2012; 308(5): 502–511.

46. Werner M, Andersson R, Olaison L, et al. A clinical study of culture -negative endocarditis. Medicine (Baltimore) 2003; 82(4): 263–273.

47. Dibble EH, Yoo DC, Noto RB. Role of PET/CT in Workup of Fever without a Source. Radiographics 2016; 36(4): 1166–1177.

48. Vilacosta I, Olmos C, de Agustín A, et al. The diagnostic ability of echocardiography for infective endocarditis and its associated complications. Expert Rev Cardiovasc Ther 2015; 13(11): 1225–1236.

49. Censullo A, Vijayan T. Using Nuclear Medicine Imaging Wisely in Diagnosing Infectious Diseases. Open Forum Infect Dis 2017; 4(1): ofx011. Dostupné z DOI: .

50. Hung BT, Wang PW, Su YJ, et al. The efficacy of 18 F -FDG PET/CT and 67Ga SPECT/CT in diagnosing fever of unknown origin. Int J Infect Dis 2017; 62: 10–17.

51. Seshadri N, Sonoda LI, Lever AM, et al. Superiority of 18F -FDG PET compared to 111In -labelled leucocyte scintigraphy in the evaluation of fever of unknown origin.J Infect 2012; 65(1): 71–79.

52. Roth AR, Basello GM. Approach to the adult patient with fever of unknown origin. Am Fam Physician 2003; 68(11): 2223–2228.

53. Tan Y, Liu X, Shi X. Clinical features and outcomes of patients with fever of unknown origin: a retrospective study. BMC Infect Dis 2019; 19(1): 198.

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