A fever of unknown origin

A fever of unknown origin

A fever of unknown origin (FUO) is a fever of at least 101°F (38.3°C) that lasts for more than three weeks or occurs frequently without explanation. Even when a doctor can’t determine the cause of the fever at first, a diagnosis is a step toward treating it.


There are four classifications of FUO.


Classic FUO affects previously healthy people. It’s defined as an unexplained fever that lasts for three weeks. Infection or neoplasms, such as leukemia, may cause classic FUO. Other disorders, such as diseases that affect connective tissue, can also be the cause.


People with nosocomial FUO appear to get a fever as a result of hospitalization. They’re admitted for something other than fever and then begin to run the unexplained fever. Common causes include:

  • pulmonary embolism
  • enterocolitis
  • sinusitis
  • deep vein thrombosis
  • septic thrombophlebitis, a type of inflammation that affects the veins


Immune-deficient FUO occurs in people with compromised immune systems. This puts them at increased risk of infection. A compromised immune system can often occur because of chemotherapy treatment.


HIV itself can cause fevers. HIV also makes a person susceptible to infections that may cause fevers.


Recognizing the type of FUO helps a physician find its cause. Causes of FUO can be categorized as any of the following:

  • infection: tuberculosis, mononucleosis, Lyme disease, endocarditis, and others
  • inflammation: lupus, rheumatoid arthritis, inflammatory bowel disease, and others
  • malignancy: lymphoma, leukemia, pancreatic carcinoma, and other cancers and sarcomas
  • miscellaneous: fevers caused by drug use or abuse,hyperthyroidism, hepatitis, and factors that don’t fit into other categories

A person with a FUO is given several clinical tests to narrow down the FUO’s classification.


FUO may be accompanied by other symptoms that can help doctors determine the underlying cause.

Typical symptoms of a fever include:

  • a temperature that exceeds 100.4°F (38°C) for babies or 99.5°F (37.5°C) for children and adults


  • sweating
  • chills
  • headaches

Other symptoms that typically accompany fever include:

  • body or joint aches
  • weakness
  • sore throat
  • fatigue
  • cough
  • rash
  • sinus congestion

Diagnostic tests for FUO

In some cases, a wait-and-see approach is often used for short-term fevers that aren’t accompanied by any red flag symptoms. Once a fever lasts long enough to be classified as a fever of unknown origin, your doctor may run some tests to determine the underlying cause.


Your doctor will likely ask if you’ve:

  • been out of the country
  • had any environmental exposures
  • had any changes in your daily environment

If you work with animals, your doctor may consider animal-borne illnesses. They’ll also ask about your family history and illnesses such as lymphoma or rheumatic fever.

Blood work and physical exam

Your doctor may also run blood tests to check for certain conditions, including autoimmune conditions that might not have many obvious symptoms. They’ll examine your skin carefully for signs of pallor, rash, or jaundice.

If blood work or the physical exam turns up any positive indicators, the doctor will order more tests before confirming a diagnosis.

Culture tests

Blood, urine, and sputum cultures may be used to check for causes such as bacteria and fungi. Special tests can also help check for atypical bacterial, fungal, or viral infections.

Imaging tests

An endocardiogram may be used to evaluate your heart if your doctor hears a murmur or strongly suspects endocarditis. This is an infection of one of the heart valves. Chest X-rays may be used to inspect the lungs.


People with FUO are discharged without a definitive diagnosis in up to 50 percent of cases. In many of these cases, FUO resolves itself in time.

Treatment for a FUO varies depending on the cause.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and antihistamines may also be used to treat FUOs that have no trace of underlying causes. In many people, these medications can help reduce the fever itself.

People whose fevers are thought to have an immune-deficient origin may be treated with broad-spectrum antibiotics. These target the most likely pathogens. Infections are responsible for between 20 and 40 percent of all fevers of unknown origin.

In people with HIV-associated fevers, treatment focuses on treating HIV with antiviral drugs. After that, any associated symptoms or complications that may stem from it will be addressed.

Recognizing FUO in children

Fevers occur commonly in children of all ages, particularly infants and toddlers. Your child may have a fever if they:

  • are less active or talkative than normal
  • have decreased appetite or increased thirst
  • have fussier behavior (especially common in infants and toddlers)
  • say that they feel warm or hot

If your child’s fever reaches 102.2°F (39°C), it should be treated. You can give them acetaminophen (Tylenol) or ibuprofen (Advil), but you should not give them aspirin (Bayer). In children, aspirin is associated with a very serious condition known as Reye’s syndrome.

Certain symptoms require immediate medical attention. This includes if your child’s fever goes up to 105°F (40.6°C). You should also contact the pediatrician if your child:

  • cries inconsolably
  • has a stiff neck
  • struggles to breathe
  • has purple rashes appear on the skin
  • has trouble waking up
  • can’t swallow


Many fevers of unknown origin are impossible to diagnose, and they can resolve without treatment. Nevertheless, a fever lasting three weeks or more can indicate a serious health issue. You should see your doctor to check for underlying causes, especially if you have other symptoms.

If you experience any emergency symptoms in combination with a fever, seek medical attention immediately. These symptoms include:

  • stiff neck
  • confusion
  • difficulty staying awake
  • chest pain
  • difficulty breathing
  • difficulty swallowing
  • repeated vomiting


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