🩺 Fever of Unknown Origin

Fever of Unknown Origin (FUO), also known as Pyrexia of Unknown Origin (PUO), describes a persistent febrile illness where the cause remains elusive after standard initial investigations. In UK practice, these cases are often categorized into four groups: classic, nosocomial, immune-deficient, and HIV-associated. Causes are broadly divided into infections, malignancies, and non-infectious inflammatory diseases (connective tissue disorders). A systematic and often repetitive diagnostic approach is required to identify the underlying trigger.

Detailed history is the most important tool. Ask about the pattern of fever (e.g., night sweats), weight loss, and fatigue. Explore potential exposures: travel history, contact with animals (zoonoses like Q fever), occupational risks, and sexual history (HIV seroconversion). Review all medications to rule out 'drug fever'. Ask about foreign travel and malaria prophylaxis compliance. A family history of autoimmune or autoinflammatory conditions (like Familial Mediterranean Fever) should also be considered if the patient is from an ethnic background where these are prevalent.

Perform a comprehensive 'top-to-toe' examination daily. Look for clues such as splinter haemorrhages or new murmurs (endocarditis), lymphadenopathy (lymphoma or HIV), and hepatosplenomegaly. Inspect the skin for rashes or vasculitic lesions and the temporal arteries for tenderness. A funduscopic exam should be performed to check for Roth spots or choroidal tubercles. Examine the joints for effusions and the spine for focal tenderness (discitis). Don't forget a digital rectal exam to look for a perianal or prostatic abscess.

Infectious (Abscess, TB, Endocarditis), Malignant (Lymphoma, RCC), Inflammatory (GCA, Adult-onset Still's disease, SLE), Drug Fever, Malaria.

Rapid weight loss, severe neutropenia, new heart murmur, travel to a malaria-endemic area, and signs of meningism.

Initial 'Tier 1' tests include FBC, U&Es, LFTs, CRP, ESR, multiple sets of blood cultures, urinalysis, and a chest X-ray. Viral serology (HIV, Hepatitis, EBV, CMV) should be performed early. If initial tests are negative, 'Tier 2' might involve CT of the chest, abdomen, and pelvis to look for occult malignancy or abscesses. 'Tier 3' may include specialized tests like PET-CT or tissue biopsies (bone marrow or liver). Echocardiography (TOE) is required if there is any suspicion of endocarditis. Always perform a malaria film for any traveller from an endemic area.

The classic definition requires a temperature over 38.3°C on several occasions over 3 weeks with no diagnosis after one week of inpatient investigation; however, modern investigations often resolve this sooner. In the UK, common 'missed' causes include lymphoma, TB, and abscesses. Do not underestimate the value of repeated physical examination—new heart murmurs (endocarditis) or rashes can appear days into admission. Always take a thorough travel history, even if the travel was months ago (e.g., malaria or brucellosis).

FUO is a complex topic that tests a student's ability to synthesize information across multiple systems. For the MLA, focus on the 'hidden' infections like TB and the systemic non-infectious causes like lymphoma or vasculitis. Understanding the staged investigation approach (starting with the least invasive) is key.