Advertisement

The yield of F18 FDG PET-CT for the investigation of fever of unknown origin, compared with diagnostic CT

  • S. Buchrits
    Correspondence
    Corresponding author at: Internal Medicine A, Beilinson Campus, Rabin Medical center, Israel.
    Affiliations
    Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
    Search for articles by this author
  • A. Gafter-Gvili
    Affiliations
    Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
    Search for articles by this author
  • Y. Eynath
    Affiliations
    Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
    Search for articles by this author
  • H. Bernstine
    Affiliations
    Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel

    Department of nuclear medicine, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
    Search for articles by this author
  • D. Guz
    Affiliations
    Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
    Search for articles by this author
  • T. Avni
    Affiliations
    Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
    Search for articles by this author
Published:August 20, 2021DOI:https://doi.org/10.1016/j.ejim.2021.07.014

      Highlights

      • PET-CT is recommended as a first or a second-line imaging method for the evaluation of patients with FUO. We evaluated the yield of PET-CT vs. contrast enhanced CT (alone) for the diagnosis of classical FUO.
      • A single center, 8-year retrospective cohort study. All hospitalized patients who underwent PET-CT for the investigation of classical FUO between were included. For each case, we determined whether the diagnosis would have been reached based on the CT scan alone, or based on the PET-CT
      • A total of 303 patients with classical FUO were referred for PET-CT.
      • PET-CT had superior sensitivity vs CT (p=0.00) for all subgroups, with generally decreased specificity than CT for infections and inflammatory conditions. PET-CT was determined as necessary in 26% (79/303) of the patients.
      • Endovascular infection, hematological malignancy and large vessel vasculitis were the only factors associated with PET-CT necessity on multivariable analysis.

      Abstract

      Background

      18F-Fluoro-2-deoxy-D-glucose (FDG) positron emission tomography, with contrast enhanced CT (PET-CT), is recommended as a first or a second-line imaging method for the evaluation of patients with fever of unknown origin (FUO). We evaluated the yield of PET-CT vs. contrast enhanced CT (alone) for the diagnosis of classical FUO.

      Methods

      A single center, 8-year retrospective cohort study. All hospitalized patients who underwent PET-CT for the investigation of classical FUO between 1/2012-1/2020 were included. The final diagnosis, based on clinical, microbiological, radiological and pathological data available at the latest follow-up, at least six months after discharge, was determined. For each case, we determined whether the diagnosis would have been reached based on the CT scan alone, or based on the PET-CT (thus, defining PET-CT as necessary). We compared the overall sensitivity and specificity results for both PET-CT and CT scan. Variables that were found to be significantly associated with PET-CT necessity on univariable analysis were entered into a multivariable logistic regression analysis. The results of the regression model were reported in odds ratios (OR) and 95% confidence intervals (CI).

      Result

      A total of 303 patients with classical FUO were referred for PET-CT. The final diagnoses included infectious diseases in 111/303 patients (36.5%), malignancies in 56/303 patients (18.4%) and non-infectious inflammatory conditions in 52/303 patients (17.1%). FUO resolved without diagnosis in 84/303 patients (28%). The overall sensitivity and specificity of the PET-CT scans were 88.7% and 80.9%, respectively, and for the CT scans were 75.2% and 90.2%, respectively. PET-CT had superior sensitivity vs CT (p=0.00) for all subgroups, with generally decreased specificity than CT for infections and inflammatory conditions. PET-CT was determined as necessary in 26% (79/303) of the patients. Endovascular infection, hematological malignancy and large vessel vasculitis were the only factors associated with PET-CT necessity on multivariable analysis.

      Conclusions

      PET-CT offers superior sensitivity with slightly decreased specificity for the diagnosis of classical FUO compared to diagnostic CT. We recommend PET-CT as the imaging modality of choice for patients with classical FUO, when endovascular infection, hematological malignancy or large vessel vasculitis are suspected.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Petersdorf RG
        • Beeson PB
        Fever of unexplained origin: report on 100 cases.
        Medicine (Baltimore). 1961; 40: 1
        • Durack DT
        • Street AC.
        Fever of unknown origin–reexamined and redefined.
        Curr Clin Top Infect Dis. 1991; 11: 35-51
        • Vanderschueren S
        • Knockaert D
        • Adriaenssens T
        • Demey W
        • Durnez A
        • Blockmans D
        • et al.
        From prolonged febrile illness to fever of unknown origin: the challenge continues.
        Arch Intern Med. 2003; 163: 1033-1041
        • Zenone T.
        Fever of unknown origin in adults: evaluation of 144 cases in a non-university hospital.
        Scand J Infect Dis. 2006; 38 (632-)
        • Meller J.
        • Sahlmann C.O.
        • Scheel A.K.
        18F-FDG PET and PET/CT in fever of unknown origin.
        J Nucl Med. 2007; 48: 35-45
        • Dong MJ
        • Zhao K
        • Liu ZF
        • Wang GL
        • Yang SY
        • Zhou GJ
        A meta-analysis of the value of fluorodeoxyglucose-PET/PET-CT in the evaluation of fever of unknown origin.
        Eur J Radiol. 2011; 80: 834-844
        • Sheng ZK
        • Ye J
        • Li JJ
        • Zhao K
        • Sheng JF.
        Utility of fluorodeoxyglucose positron emission tomography/computed tomography in patients with fever of unknown origin diagnosed as lymphoma.
        Med Principles Pract: Int J Kuwait Univ Health Sci Centre. 2014 Jul 17; (PubMed PMID: 25034855)
        • Blockmans D
        • Knockaert D
        • Maes A
        • De Caestecker J
        • Stroobants S
        • Bobbaers H
        • et al.
        Clinical value of [(18)F]fluoro-deoxyglucose positron emission tomography for patients with fever of unknown origin.
        Clin Infect Dis: Off Public Infect Dis Soc Am. 2001; 32: 191-196
        • Gafter-Gvili A
        • Raibman S
        • Grossman A
        • Avni T
        • Paul M
        • Leibovici L
        • et al.
        [18F]FDG-PET/CT for the diagnosis of patients with fever of unknown origin.
        QJM: Mon J Assoc Phys. 2015; 108: 289-298
      1. Keidar, Z., Gurman-Balbir, A., Gaitini, D., & Israel, O. (n.d.). Fever of Unknown Origin: The Role of 18F-FDG PET/CT. https://doi-org.beilinson-ez.medlcp.tau.ac.il/10.2967/JNUMED.108.054692.

        • Hao R
        • Yuan L
        • Kan Y
        • Li C
        • Yang J.
        Diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin: a meta-analysis.
        Nucl Med Commun. 2013; 34 (Jul PubMed PMID: 23636293): 682-688
        • Bleeker-Rovers CP
        • Vos FJ
        • Mudde AH
        • Dofferhoff ASM
        • de Geus-Oei LF
        • Rijnders AJ
        • et al.
        A prospective multi-centre study of the value of FDG-PET as part of a structured diagnostic protocol in patients with fever of unknown origin.
        Eur J Nucl Med Mol Imaging. 2007; 34: 694-703
        • Unger M
        • Karanikas G
        • Kerschbaumer A
        • Winkler S
        • Aletaha D.
        Fever of unknown origin (FUO) revised.
        Wien Klin Wochenschr. 2016; 128: 796-801
        • Brown M.
        Pyrexia of unknown origin 90 years on: a paradigm of modern clinical medicine.
        Postgrad Med J. 2015; 91: 665-669
        • Saif MW
        • Tzannou I
        • Makrilia N
        • Syrigos K.
        Role and cost effectiveness of PET/CT in management of patients with cancer.
        Yale J Biol Med. 2010; 83: 53-65
        • Khwaja A.
        KDIGO clinical practice guidelines for acute kidney injury.
        Nephron Clin Pract. 2012; 120: c179-c184
        • Zerizer I.
        • et al.
        Role of FDG-PET and PET/CT in the diagnosis and management of vasculitis.
        Eur J Radiol. 2010; 73: 504-509
        • Kermani T.A.
        • et al.
        Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis.
        Ann Rheum Dis. 2013; 72: 1989-1994
      2. Ben Shimol J, Amital H, Lidar M, Domachevsky L, Shoenfeld Y, Davidson T. The utility of PET/CT in large vessel vasculitis. Sci Rep. 2020 Oct 19;10(1):17709. doi: 10.1038/s41598-020-73818-2. PMID: 33077771; PMCID: PMC7572466.

        • Jiemy W.
        • et al.
        Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of macrophages in large vessel vasculitis: current status and future prospects.
        Autoimmun. Rev. 2018; 17: 715-726
        • Mahmood M
        • Kendi AT
        • Ajmal S
        • Farid S
        • O'Horo JC
        • Chareonthaitawee P
        • Baddour LM
        • Sohail MR
        Meta-analysis of 18F-FDG PET/CT in the diagnosis of infective endocarditis.
        J Nucl Cardiol. 2019; 26 (Jun Epub 2017 Oct 30. PMID: 29086386): 922-935https://doi.org/10.1007/s12350-017-1092-8
        • Habib G.
        • et al.
        2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM).
        Eur Heart J. 2015; 36 (Nov 21): 3075-3128
        • Georga S
        • Exadaktylou P
        • Petrou I
        • Katsampoukas D
        • Mpalaris V
        • Moralidis EI
        • Arvaniti K
        • Papastergiou C
        • Arsos G.
        Diagnostic value of 18F-FDG-PET/CT in patients with FUO.
        J Clin Med. 2020; 9 (Jul 4 PMID: 32635566; PMCID: PMC7408628): 2112https://doi.org/10.3390/jcm9072112
        • Gallagher BM
        • Fowler JS
        • Gutterson NI
        • et al.
        (1978) Metabolic trapping as a principle of radiopharmaceutical design: some factors responsible for the biodistribution of [18F] 2-deoxy-2-fluoro-D-glucose.
        J Nucl Med. 1978; 19 (PMID:214528): 1154-1161
        • Vitola J.V.
        • Dondi M.
        • Prado P.
        • Shaw L.
        • Paez D.
        Worldwide availability and utilization of PET/CT from IAEA survey: potential for nuclear cardiology applications.
        Ann Nuclear Cardiol. 2019; 5 (https://doi-org.beilinson-ez.medlcp.tau.ac.il/10.17996/anc.19-00103): 44-46