Fever of Unknown Origin / Pyrexia of unknown origin

Fever of unknown origin (FUO), also known as pyreia of unknown origin (PUO), is a condition in which fever in excess of 38.3C has been around for three weeks or longer, and persists despite three outpatient evaluations or 3 days in the hospital. Despite extensive investigations and initial treatment, fever persists and as the name suggests, the cause of the febrile illness is often not identified during the initial workup. 

FUO / PUO can occur in otherwise healthy individuals, hospitalized patients, immunocompromised patients or patients with human immunodeficiency virus.

As mentioned above, it is characterised by a prolonged febrile illness and depending on its cause, the constellation of signs and symptoms may vary. 

It may present as an isolated febrile illness or it could be associated with other symptoms such as headaches, joint pains, rash, lymph node enlargement, loss of weight, loss of appetite, shortness of breath, chronic cough, chronic diarrhoea. This list of common clinical signs and symptoms is not exhaustive. 

There are many causes of FUO / PUO, ranging from infections to autoimmune diseases to malignancies.  Some common causes of FUO / PUO include the following:

Unfortunately, in 10-20% of cases, the cause of the FUO / PUO remain undiagnosed.

The diagnosis of FUO / PUO is based on comprehensive history and physical examination. Repeated consults to retake the history and repeat physical examination is often necessary to help the physicians make the diagnosis and find out the exact cause of the prolonged fever. 

The wide range of tests performed thereafter are often adjuncts to help the physician make the diagnosis. The tests include blood tests, key imaging studies and may include invasive diagnostic procedure.  The selection of tests is guided by the presenting clinical complaint. 

More than the technology involved, getting to the root cause of FUO / PUO requires experienced clinicians, as well as patience on the part of patient and his/her family. Often, a multi-disciplinary team of doctors is involved. This is usually led by the infectious diseases team to pinpoint the exact cause of the FUO / PUO.