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.
Osteomyelitis
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
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:
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C burnetii infection
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Choledocholithiasis
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Drug Fever
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Empyema, Gallbladder
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Empyema, Pleuropulmonary
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Gallbladder Gangrene
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Hepatitis A-E
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Hepatoma
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Intra-abdominal Sepsis
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Lyssavirus Infection
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Malassezia furfur Infection
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Miliary Tuberculosis
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Nonarticular Rheumatism/Regional Pain Syndrome
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Prostatic Abscess
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Rat-bite Fever (S minor)
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SARS-Covid 19
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Sphenoid Sinusitis
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West Nile Virus
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Zika Virus
Differential Diagnoses
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Appendicitis
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Tender subcutaneous nodules on the anterior shin and foot in an individual with polyarteritis nodosa
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Early rash of systemic lupus erythematosis. Rashes occurring the setting of FUO may be biopsied for diagnosis.[ From eMedicine article, Subacute Cutaneous Lupus Erythematosis]
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Sweet syndrome may herald a hematologic malignancy
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Psoas abscess may cause fevers, but it may be secondary to another condition that may cause FUO, including endocarditis, gastrointestinal or urologic malignancy or infection, vertebral osteomyelitis, or occult intravenous drug use. In this case, an enteric fistula due to underlying Crohn's disease was the culprit.
