(Last Updated On: January 19, 2016)

Chapter 4 – “Fever of Unknown Origin”


Welcome to the fourth installment of “Inconceivable: medical terms that don’t mean what you think they mean.”

You are taking care of a patient sent in from his PCP to be admitted for an intermittent fever for the past two weeks. He has no localizing infectious symptoms, he is nontoxic in appearance and his physical exam is unremarkable except for a temperature of 38.5 °C. His work up including labs, UA, and chest x-ray are notable only for a leukocytosis.

When you call the admitting team to give report, you state that the patient will be admitted for “fever of unknown origin.” Although your patient does have a fever and you haven’t yet figured out the source, “fever of unknown origin” is a term with very specific criteria that your patient doesn’t meet. Let’s take a closer look.

Fever of Unknown origin (FUO) requires three things:1

  1. Temperature greater than 38.3 °C (101 °F)
  2. Greater than 3 weeks duration of illness
  3. Failure to determine the source despite appropriate inpatient evaluation.

The original definition of FUO from 1961, and the one that some sources still adhere to, requires a full week of inpatient work up.2 Unsurprisingly, improvements in medical diagnostics – particularly advanced imaging and serology – have continuously changed our understanding of FUO as we are able to diagnose and treat many more pathologies.3  As such, most now do not feel a full week of inpatient treatment is needed to label FUO if there has been an appropriate work up in the hospital.

The most common sources for FUO are infections, neoplasms, and autoimmune disorders, but approximately 5-15% of FUO remain undiagnosed despite exhaustive work ups. Although we can’t officially diagnose FUO in the ED (unless the patient is a bounce-back), there are a number of sources of fever in the ED that often go overlooked and are relatively easy to diagnose if we consider them:

  • Abscesses – Although one would expect localizing symptoms in a patient with an abscess, this is not always the case, particularly in the abdomen and pelvis.
  • HIV – Just send the test, especially if you are admitting the patient (after obtaining patient consent, of course).
  • Venous thromboembolism – Up to a 1/3 of patients with PE may present with fevers without another cause.4
  • Syphilis – Does your patient have a rash? If so, it could be syphilis. Any rash? Yes, pretty much any rash can be syphilis. Yes, even in geriatric patients. A sexually active septuagenarian I recently tested for STI told me, “I didn’t know us old people could get those kinds of infections!”


Dr. Krueger is currently an attending physician at Advocate Lutheran General Hospital and a former UIC EM Chief Resident.



  1. Fever of Unknown Origin. Retrieved December 31, 2015, from http://emedicine.medscape.com/article/217675-overview#a5
  2. Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases.Medicine. 1961;40:1–30.
  3. Ergönül O, Willke A, Azap A, et al. Revised definition of ‘fever of unknown origin’: limitations and opportunities.J Infect. 2005 Jan. 50(1):1-5.
  4. Kokturk N, Demir N, Oguzulgen IK, Demirel K, Ekim N. Fever in pulmonary embolism.Blood Coagul Fibrinolysis. 2005 Jul;16(5):341-7