Key Feature 4: Investigate patients with fever of unknown origin appropriately (ex: with blood cultures, echocardiography, bone scans).
Skills: Clinical Reasoning
Key Feature 5: In febrile patients, consider life-threatening infectious causes (ex: endocarditis, meningitis).
Phase: Hypothesis generation, Diagnosis
Key Feature 5: In immigrants presenting with a new or ongoing medical condition, consider in the differential diagnosis infectious diseases acquired before immigration (ex: malaria, parasitic disease, tuberculosis).
Skill: Clinical Reasoning, Selectivity
Phase: Hypothesis generation
In a patient presenting with a fever, usually with a good history and physical examination, the clinician can find some clues as to what may be going on (the general differential diagnosis includes infection, neoplasm, inflammatory conditions, and drug toxicity, among others). Sometimes, however, there are no symptoms or signs that suggest a reason for the fever, and per the UpToDate article, Approach to the adult with fever of unknown origin (2018), this is best called "fever without localising signs" after initial clinical assessment. If a thorough history and physical examination and a sufficient preliminary workup are unrevealing, and if the fever lasts greater than 2-3 weeks, then this can now take on the diagnostic label of "fever of unknown origin (FUO)." (Note that the definition of FUO for pediatric patients is less demanding, with a duration requirement of only 8 days to meet this diagnostic criteria per the UpToDate article, Fever of unknown origin in children: Evaluation (2018).) Between the time that a persistent fever becomes one that is "without localising signs" to one that is "of unknown origin," the most important thing a clinician can do is continue to clinically reassess and investigate if there are whiffs of something going on that can be measured or caught in a radiograph etc. If the patient is otherwise stable, empiric therapy may not be warranted, and a watch-and-wait approach is preferred. But if the duration of fever tips into the timeline of FUO, it's time to do a more extensive workup. I have outlined the initial workup for a fever without localising signs and a fever of unknown origin per the UpToDate article, Approach to the adult with fever of unknown origin (2018):
Investigations warranted in a patient who has fever without localising signs:
Investigations warranted in a patient who has fever of unknown origin:
*Although not routinely indicated as part of the basic workup in a patient with FUO without positive blood cultures, according to the UpToDate article, Etiologies of fever of unknown origin in adults (2018), "Cultures are negative in 2 to 5 percent of patients with infective endocarditis even when the utmost care is taken in obtaining the proper number and volume of blood cultures. The frequency of negative cultures is higher in patients who have already been treated with antimicrobials, such as intravenous drug users who frequently self-administer antibiotics."