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Fever of Unknown Origin Treatment & Management

  • Author: Kirk M Chan-Tack, MD; Chief Editor: Michael Stuart Bronze, MD  more...
Updated: Sep 14, 2015

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.


Inpatient Treatment

No evidence supports prolonged hospitalization in 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.



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

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

Contributor Information and Disclosures

Kirk M Chan-Tack, MD Medical Officer, Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration

Disclosure: Nothing to disclose.


John Bartlett, MD Professor Emeritus, Johns Hopkins University School of Medicine

John Bartlett, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Pharmacology, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, American Thoracic Society, American Venereal Disease Association, Association of American Physicians, Infectious Diseases Society of America, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: American College of Physicians, Alliance for the Prudent Use of Antibiotics, The Foundation for AIDS Research, Southern Society for Clinical Investigation, Southwestern Association of Clinical Microbiology, Association of Professors of Medicine, Association for Professionals in Infection Control and Epidemiology, American Clinical and Climatological Association, Infectious Disease Society for Obstetrics and Gynecology, Orleans Parish Medical Society, Southeastern Clinical Club, American Association for the Advancement of Science, Alpha Omega Alpha, American Association of University Professors, American Association for Physician Leadership, American Federation for Medical Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association of American Medical Colleges, Association of American Physicians, Infectious Diseases Society of America, Louisiana State Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southern Medical Association

Disclosure: Received royalty from Baxter International for other.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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