Fever of Unknown Origin

  • Basics

    Fever is a protective response to infection and injury. An elevated temperature enhances the body’s innate defense mechanisms by making conditions less favorable for infectious microorganisms to thrive. An elevated body temperature, for example, decreases the levels of iron in the bloodstream, thus inhibiting the growth of some microorganisms. People with fevers also tend to eat less and rely more on fat and protein sources for energy, which decreases the blood glucose levels upon which bacteria normally thrive. In addition, there are some microorganisms that are heat-sensitive, and do not grow well at elevated body temperatures.

    Unexplained fevers that continue for more than three weeks are referred to as fever of undetermined origin (FUO). FUO is classically identified by the following elements:

    • A temperature higher than 101°F (38.3°C) on several occasions
    • A fever that lasts longer than three weeks
    • Failure to find the underlying cause(s) of the fever, despite one week of inpatient investigation or three outpatient visits

  • Causes

    Infections are the most common cause of fever Table 01. FUO is most commonly caused by infectious diseases. When an infection occurs, invading organisms trigger a cascade of events in the immune system, one of which releases chemicals that instruct the body to raise its core temperature. Common examples that may lead to FUO include tuberculosis, mononucleosis, HIV, pneumonia, and meningitis, among others. However, FUO can result from almost any bacterial, viral, or fungal infection if that infection is not diagnosed or treated promptly.

    Table 1.  Common Infectious Causes of Fever

    Infective endocarditis

    Unrecognized cancers can cause FUO. The most common malignant or cancerous disorders that can cause a FUO include leukemia, Hodgkin’s disease, and colorectal cancer. Any cancer that spreads to the liver or central nervous system can also cause FUO.

    Collagen vascular diseases can cause FUO. Collagen vascular disease, which encompasses widespread damaging changes in connective tissue, can also cause FUO. Polymyalgia rheumatica and giant-cell arteritis are two especially common causes in the elderly. Lupus sarcoidosis is a common cause in middle-aged women.

    Certain drugs and medications can produce FUO. Medications such as antibiotics, antihistamines, barbiturates, drugs for high blood pressure, and antipsychotics such as Haldol, the phenothiazines, lithium, and reserpine can produce FUO. This reaction can happen weeks or months after medication has been started, or after it has been completed.

    Various other conditions are known to cause FUO. Other known causes of FUO include inflammatory bowel disease, various abscesses, and juvenile rheumatoid arthritis.

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