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Fevers of Unknown Origin (FUO)

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 (FEVER OF UNKNOWN ORIGIN) affects previously healthy people. It is 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 because of hospitalization. They are 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 




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, cat scratch fever, 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 do not fit into other categories.  


A person with an FUO is given several clinical tests to narrow down the FUO’s classification. Diagnosis of the FUO can also draw attention to an otherwise undiagnosed condition. 




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




  • Our specialists will ask if you have: 

  • Been out of the country. 

  • Had any environmental exposures. 

  • Had any changes in your daily environment. 


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


Blood work and physical exam 


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

If blood work or the physical exam turns up any positive indicators, our specialists 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 our specialist 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. 




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 twenty and forty 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. 




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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