Fever of Unknown Origin (FUO) Treatment & Management

Updated: May 17, 2021
  • Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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Approach Considerations

In general, empiric therapy has little or no role in cases of classic fever of unknown origin (FUO).

Treatment should be directed toward the underlying cause, as needed, once a diagnosis is made.

Some studies suggest a few exceptions to this general approach, including the following:

  • Cases that meet criteria for culture-negative endocarditis
  • Cases in which findings or the clinical setting suggests cryptic disseminated TB (or, occasionally, other granulomatous infections)
  • Cases in which temporal arteritis with vision loss is suspected

Several studies have found that prolonged undiagnosed FUO generally carries a favorable prognosis.

Because of a better understanding of the etiologies and careful diagnostic approaches, patients with FUO rarely need surgical treatment.

Specific examples of treatment

In patients with hepatic granulomas, approximately 50% of patients recover spontaneously, while the other 50% respond to corticosteroid treatment (duration of therapy ranging from a few weeks to several years).

Patients with giant cell arteritis should be treated with high doses of steroids, and intravenous steroids should be administered if the patient is very ill or has significant ocular compromise. Carefully monitor the patient, since inadequate treatment and steroid toxicities (eg, hypertension, diabetes, dyspepsia, bone loss, psychosis, cataracts) can cause significant morbidity.

In polymyalgia rheumatica, the treatment consists of amelioration of symptoms with steroid therapy and close monitoring for possible development of GCA.

When drug fever is suspected, discontinue the implicated drug. Stopping the causative drug generally leads to defervescence within 2 days.


Inpatient Treatment

No evidence supports prolonged hospitalization of patients who are clinically stable and whose workup findings are unrevealing.


Outpatient Care

Conduct close follow-up procedures and systematic reevaluation studies to prevent clinical worsening. Guide further workup studies on an outpatient basis.


Patient Transfer

The need for transfer is indicated if (1) the current facility is unable to establish a diagnosis, (2) diagnostic tests are unavailable at the existing facility, or (3) the patient deteriorates clinically such that necessary level of care or consultations is unavailable.



Appropriate consultations are indicated based on patient history, physical examination, laboratory data, and radiologic findings. Consultations include the following:

  • Infectious disease specialist
  • Hematologist/oncologist
  • Rheumatologist
  • Pulmonologist
  • Gastroenterologist
  • Endocrinologist
  • Interventional radiologist
  • Surgeon

Long-Term Monitoring

The 5%-15% of patients whose FUO remains undiagnosed, even after extensive evaluations, usually have a benign long-term course, but close follow-up and systematic reevaluation studies are essential to avoid missing potential etiologies.