Fever of Unknown Origin (FUO) Differential Diagnoses

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

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

Hepatobiliary infections

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.

Parasitic infections

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.

Drug fever

A history of allergy, skin rashes, or peripheral eosinophilia is often absent in cases of drug fever.


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

Collagen-vascular and autoimmune diseases

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.

Conditions to consider in the diagnosis of FUO

More than 200 conditions may cause FUO and include the following, as well as the disorders in the Differentials subsection, below:

Differential Diagnoses