{"entity":{"id":"fever-of-unknown-origin","kind":"indication","name":"Fever of unknown origin","aka":[],"tldr":"When a persistent fever has no obvious cause after the usual tests, a whole-body PET scan using the same sugar tracer as cancer imaging often lights up the hidden infection, inflammation or tumour behind it.","summary":"Fever of unknown origin (FUO) is classically defined as a fever above 38.3C persisting for at least three weeks with no diagnosis despite three outpatient visits or three days as an inpatient; a related entity, inflammation of unknown origin (IUO), is unexplained, persistently raised inflammatory markers without fever. Causes span infection, autoimmune and inflammatory disease, and malignancy, and in a substantial fraction of patients no cause is ever found. Because FDG PET/CT can survey the entire body at once for areas of increased glucose metabolism, it has become the nuclear medicine test of choice for this problem once routine work-up (history, examination, standard blood tests and cultures, chest imaging) has failed to find a cause.\n\nThe joint 2024 SNMMI/Infectious Diseases Society of America/American College of Nuclear Medicine appropriate use criteria rate FDG PET/CT as appropriate for both adult and paediatric FUO, and reserve older techniques - gallium-67 scintigraphy and radiolabelled leukocyte scintigraphy - for situations in which FDG PET/CT is unavailable, with leukocyte scintigraphy specifically for cases where infection is strongly suspected. The 2024/2025 EANM/SNMMI FDG hybrid PET guideline for infection and inflammation gives protocol detail specific to this indication: the scan should ideally be performed before, or as early as possible after, starting antibiotics or oral glucocorticoids, since both can suppress the very uptake being sought, and myocardial suppression preparation should be considered if endocarditis or cardiac sarcoidosis is part of the differential.\n\nDiagnostic yield, rather than sensitivity or specificity in isolation, is the relevant performance measure, because many patients with FUO never get a final causative diagnosis by any test; FDG PET/CT is valued for how often it identifies a focus that can be biopsied or otherwise pinned down, and for its high negative predictive value - a negative scan is associated with a good prognosis and can support a watch-and-wait approach rather than further invasive testing.","asOf":"2026-09-22","links":[{"label":"SNMMI appropriate use criteria factsheet: fever of unknown origin","url":"https://snmmi.org/common/Uploaded%20files/AUC%20Factsheets/Fever_of_Unknown_Origin_AUC_Factsheet.pdf"},{"label":"EANM/SNMMI guideline/procedure standard for FDG hybrid PET use in infection and inflammation in adults v2.0","url":"https://link.springer.com/article/10.1007/s00259-024-06915-3"},{"label":"SNMMI: new appropriate use criteria for FUO (news summary)","url":"https://axisimagingnews.com/radiology-products/imaging-equipment/nuclear-medicine/snmmi-issues-new-guidelines-for-diagnosing-fever-of-unknown-origin"}],"tags":["infection","PET","inflammation"],"related":["infection-prosthetic-joint","ga-67"],"indications":[],"sections":[],"technologies":["fdg-pet","pet-ct"],"targets":[],"drugs":["fludeoxyglucose-f18"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"infection","burden":"FUO is an uncommon but recurrent diagnostic problem in general and infectious disease practice; systematic reviews put a final diagnosis within reach in roughly half to two-thirds of cases after full modern work-up, with infection, malignancy, and non-infectious inflammatory disease each accounting for a substantial share of identified causes.","subtypes":[],"biomarkers":[],"standardOfCare":[{"setting":"Adult or paediatric FUO/IUO without a diagnosis after standard work-up","approach":"Whole-body FDG PET/CT, performed early in the work-up where possible and ideally before or within days of starting corticosteroids or antibiotics.","refs":["fludeoxyglucose-f18"]},{"setting":"FDG PET/CT unavailable, or strong clinical suspicion of infection specifically","approach":"Gallium-67 scintigraphy or radiolabelled leukocyte scintigraphy as second-line nuclear imaging options.","refs":[]}],"stateOfArt":["The 2024 SNMMI/IDSA/ACNM appropriate use criteria formalise FDG PET/CT as the nuclear medicine test of choice for FUO in adults and children, a shift from the historical role of gallium and leukocyte scintigraphy.","The EANM/SNMMI FDG hybrid PET guideline v2.0 (2024/2025) covers fever/inflammation of unknown origin as the first of 19 defined infection and inflammation indications, with specific advice on timing relative to glucocorticoid therapy and on myocardial suppression when a cardiac source is possible.","Cost-effectiveness analyses cited in the EANM consensus document support using FDG PET/CT early in the diagnostic pathway rather than as a last resort, since it can shorten the overall diagnostic process."],"history":[],"pipeline":[],"openProblems":["A meaningful fraction of patients with FUO remain without a final diagnosis even after FDG PET/CT, and the guideline explicitly notes insufficient evidence for its use in patients with normal inflammatory markers.","Interpretation is complicated by physiological brown fat, bowel and myocardial uptake, and by uptake from unrelated incidental findings, all of which require correlation with contrast CT or MRI.","Access and cost mean gallium and leukocyte scintigraphy remain in use in settings without ready PET/CT availability, despite their inferior performance."]},"route":"/indications/fever-of-unknown-origin/","neighbours":{"indication":[{"id":"infection-prosthetic-joint","kind":"indication","name":"Prosthetic joint infection","route":"/indications/infection-prosthetic-joint/"}],"isotope":[{"id":"ga-67","kind":"isotope","name":"Gallium-67","route":"/isotopes/ga-67/"}],"technology":[{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"}],"drug":[{"id":"fludeoxyglucose-f18","kind":"drug","name":"Fludeoxyglucose F-18 (FDG)","route":"/drugs/fludeoxyglucose-f18/"}]}}