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Fever of Unknown Origin Differential Diagnoses

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

Diagnostic ConsiderationsHepatobiliary infectionsOsteomyelitisParasitic infectionsDrug feverTuberculosisCollagen-vascular and autoimmune diseasesConditions to consider in the diagnosis of FUO

Approximately 5-15% of patients with fever of unknown origin (FUO) remain undiagnosed, even after extensive evaluations.

Acute cholecystitis and gallbladder empyema can lead to a diagnosis of FUO because of the lack of right upper quadrant pain or jaundice, especially in elderly patients.

The most common reason for misdiagnosis of osteomyelitis is the failure to consider the disease in a patient who is febrile with musculoskeletal symptoms.

If the physician is unaware of a history of recent travel to an endemic area and if the fever pattern is nonsynchronized, malaria can be missed as a cause of fever.

A history of allergy, skin rashes, or peripheral eosinophilia is often absent in cases of drug fever. Neither the fever pattern nor the duration of previous therapy is helpful in establishing the diagnosis.

Tuberculosis (TB) is usually considered in the FUO differential diagnoses; however, several factors may prevent a prompt diagnosis of TB. In TB, dissemination, which usually occurs in immunocompromised patients, may initially manifest as constitutional symptoms that lack localizing signs.

Consider PAN, RA, and mixed connective-tissue diseases in patients with FUO, because of the potential for nonspecific presentations in these diseases. Rheumatic fever can be difficult to diagnose, because it is rare in the developed world.

Diseases to consider in patients with symptoms of FUO include the following, as well as the disorders in the Differentials subsection, below:

Differential Diagnoses

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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