Fever of Unknown Origin

Definition

An elevated temperature that eludes diagnosis is given the term “fever of unknown origin,” or FUO. A FUO has been defined as an intermittent temperature of at least 101°F for over three weeks with at least a week’s worth of attempts to find the cause.

Generally, the cause of a fever is obvious—usually it is an infection, and usually the site of the infection and the nature of the infecting agent are easy to figure out. When the usual investigations yield no answer, yet the fever persists, a tentative diagnosis of FUO is made until the cause can be identified.

Causes

There are many rare causes of temperature elevation. Sifting through them for the right answer challenges many a good physician. The following list is by no means exhaustive but merely includes the most common of the uncommon causes. Over 140 separate diseases are listed in Harrison’s Principles of Internal Medicine .

• Unusual infections
  • Extrapulmonary (located elsewhere than in the lungs) tuberculosis
  • Atypical tuberculosis (relatives of the common germ)
  • Tropical diseases in temperate climates/latitudes—malaria, dengue fever, yellow fever, etc
  • Rare organisms—fungi, viruses, uncommon bacteria
• Obscure infections
  • Prostatitis
  • Sinusitis
  • Hidden abscesses
• Collagen vascular (connective tissue, autoimmune) diseases
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
• Inflammatory diseases
  • Sarcoidosis
  • Crohn’s disease (regional ileitis)
• Cancer
  • Lymphoma ( Hodgkin’s and non-Hodgkin’s )
  • Leukemia
  • Kidney cancer
  • Liver cancer
• Drug reactions
  • Antibiotics
  • Epilepsy medications
  • Immune globulin
  • Antipsychotics (eg, Thorazine, Haldol)
  • Antihistamines
• Hormone disturbances
  • Hyperthyroidism
• Hereditary metabolic diseases
• Brain disorders that affect temperature regulation
  • Tumors
  • Strokes

Risk Factors

The following factors increase your chance of developing a FUO. If you have any of these risk factors, tell your doctor:

• Foreign travel, especially to developing and tropical countries
• Current medications (both prescription and over-the-counter)
• Cancer or brain tumor
• Collagen vascular disease (an autoimmune disorder of connective tissue)
• HIV/AIDS
• Current or recent hospitalization
• Similar problems in your family

Symptoms

If you experience any of these symptoms, do not assume it is due to a FUO. A fever is a very common indication of many problems, both serious and trivial. If you experience any one of them, see your physician.

• Elevated temperature by thermometer reading
• Sweats
• Chills
• Aching all over

Diagnosis

Your doctor will ask about your symptoms and medical history, and perform a physical exam. You can help by taking your temperature with a thermometer several times a day. Your primary care physician may refer you to a specialist in infectious diseases or possibly oncology. The first efforts after the usual evaluation will be to narrow the possibilities by examining the circumstances under which the fever began. Were you traveling abroad? Were you hospitalized? Is your immune system damaged, for example by AIDS? What medications are you currently taking?

Many different tests may be indicated at some point in evaluating a FUO. Tests may include the following:

• Exhaustive studies of blood, urine, and all other bodily products
• Exhaustive imaging studies: x-rays, CT and MRI scans, ultrasound examinations
• Nuclear medicine studies
• Endoscopies (lungs, stomach and intestines, sinuses, etc.)
• Biopsies (samples taken by knife or needle) of suspect tissues

Treatment

There is no treatment for a FUO until the underlying disease is identified. When its cause is discovered, treatment will follow.

Prevention

There are so many causes for a FUO that prevention includes everything one does to stay healthy. One important item needs mentioning: be sure to take all preventive measures recommended by the public health department when you travel abroad.