Fever of Unknown Origin Diagnosis

  • Diagnosis

    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

    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

    Tuberculosis
    Mononucleosis
    Cytomegalovirus
    HIV
    Infective endocarditis
    Histoplasmosis
    Pneumonia
    Appendicitis
    Meningitis
    Osteomyelitis

    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.

    The primary symptom of FUO is a temperature higher than 101°F (38.3°C) on several occasions that lasts longer than three weeks. Additional symptoms may be dependent on the underlying cause of the FUO. For example, lower extremity weakness, back pain, and a history of urinary tract infection may indicate that FUO is caused by osteomyelitis—especially in patients with prosthetic devices. An accompanying heart murmur may indicate that infective endocarditis is the cause of FUO.

    Risk factors depend on the underlying cause of FUO. Since infections account for the majority of FUO cases in adults, exposure to infectious microorganisms is a common risk factor, and should be avoided.

    Patients who have undergone a solid organ or bone marrow transplant, or who received blood products, are at an increased risk for cytomegalovirus infection, which can lead to FUO. People who have had abdominal trauma or surgery may have an increased risk of developing an abscess, which can also lead to FUO.

    Your doctor will take a complete medical history. A thorough medical history is vital for determining the underlying cause of the fever. Tell your doctor about any illnesses or injuries you may have had, any exposure to people who are or were ill, any recent travel (even local), all medications you are taking (including over-the-counter drugs), and any exposure to animals, plants, insects, or chemicals.

    Your doctor will perform a physical examination to look for any obvious signs and symptoms, and to help direct further diagnostic testing. Once a medical history is taken, you will be given a complete physical examination. Your doctor will examine you for facial pain, swollen glands, oral ulcers, rash, insect bites, heart murmur, enlarged spleen and liver, neck stiffness, abdominal or rectal masses or tenderness, decreased sensitivity to pain, or other signs and symptoms that appear out of the ordinary.

    Initial screening tests are done to help pinpoint the underlying cause of the FUO. More specific diagnostic tests are performed when an underlying cause is suspected. In addition to the medical history and physical examination, initial screening tests may be performed to help determine the underlying cause of FUO, and to help guide the choice of further diagnostic tests. Some of these initial screening tests include:

    • A complete blood count
    • A basic metabolic panel
    • Erythrocyte sedimentation rate
    • Liver function enzyme levels
    • HIV screen (only with documented patient consent)
    • Syphilis screen
    • Urinalysis with culture
    • Sputum culture
    • Fecal exam
    • Blood cultures
    • Chest x-ray
    • Tuberculosis test

    Further screening tests will follow once your doctor suspects an underlying cause of FUO. After basic lab tests have been run, diagnostic tests such as ultrasonography, CT scans, and radioactive white blood scans can be used to pinpoint the cause of the fever. Medication that may be inducing fever should be discontinued until the cause of the fever can be determined.

    Avoid contact with people who have contagious infectious diseases. If contact cannot be avoided, be sure to wash your hands frequently to avoid transmission. Infectious diseases are the most common cause of FUO. Therefore, avoid contact with people who have contagious infectious diseases. Washing your hands frequently can also reduce the risk of transmission from an infected person.

  • Prevention and Screening

    Avoid contact with people who have contagious infectious diseases. If contact cannot be avoided, be sure to wash your hands frequently to avoid transmission. Infectious diseases are the most common cause of FUO. Therefore, avoid contact with people who have contagious infectious diseases. Washing your hands frequently can also reduce the risk of transmission from an infected person.

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