Fever of unknown origin

FUO Definition & Causes - The Usual Suspects

• Classic Definition (Petersdorf & Beeson):

  • Fever > 38.3°C (> 101°F) on several occasions.
  • Duration ≥ 3 weeks.
  • No diagnosis after 3 outpatient visits or 3 days of inpatient investigation.

• Major Etiologies (The "Big Three"):

  • Infections (~30-40%): Most common cause.
    • Abscesses (abdominal, pelvic), Tuberculosis (especially extrapulmonary), Endocarditis (culture-negative).
  • Neoplasms (~20-30%):
    • Lymphoma (Hodgkin & Non-Hodgkin), Leukemia, Renal Cell Carcinoma.
  • Collagen Vascular/Autoimmune (~10-20%):
    • Adult-onset Still's disease, Systemic Lupus Erythematosus (SLE), Giant Cell Arteritis (in elderly).

⭐ In elderly patients (>65 years), connective tissue diseases (like Giant Cell Arteritis) and malignancies are more frequent causes of FUO than infections.

FUO Workup - Diagnostic Detectives

• Initial Phase (Clue Hunting):

  • Thorough history (travel, exposures, meds) & physical exam.
  • Labs: CBC with diff, ESR/CRP, LFTs, ANA, RF.
  • Blood cultures: 3 sets from different sites, off antibiotics.
  • Urinalysis & culture.
  • CXR.

• Secondary Phase (Imaging):

  • CT Abdomen/Pelvis is the cornerstone imaging study.
  • Consider transthoracic echo (TTE) if endocarditis suspected.

• Advanced/Invasive Phase:

  • FDG-PET/CT scan can localize inflammation or malignancy.
  • Biopsy of suspicious findings (e.g., lymph node, skin lesion, temporal artery for GCA if ESR ↑ & age >50).

⭐ In adults, the "Big 3" causes of classic FUO are: Infections (~30%), Neoplasms (~20%), and Collagen Vascular/Autoimmune diseases (~15%).

Endocarditis Essentials - Heart of the Matter

• Presentation: Fever, new/changed heart murmur, and embolic phenomena. Acute (e.g., S. aureus) vs. Subacute (e.g., Viridans streptococci on damaged valves).
• Classic Signs (📌 FROM JANE):
  • Fever, Roth spots, Osler nodes (painful), Murmur, Janeway lesions (painless), Anemia, Nail-bed (splinter) hemorrhages, Emboli.
• Diagnosis (Modified Duke Criteria):
  • Requires 2 major, 1 major + 3 minor, or 5 minor criteria.
  • Major: Sustained bacteremia by typical organism, endocardial involvement on echocardiogram (vegetation, abscess).

⭐ Streptococcus gallolyticus (formerly S. bovis) bacteremia has a strong association with underlying colorectal cancer; colonoscopy is warranted.

• Fever of Unknown Origin (FUO) is a temperature > 38.3°C lasting > 3 weeks without a diagnosis after a comprehensive workup.
• The classic triad of causes includes infection (especially occult abscesses, TB, endocarditis), malignancy (lymphoma), and autoimmune disease (Still's disease, vasculitis).
• Always consider culture-negative endocarditis (Coxiella, Bartonella) as a potential source.
• CT imaging of the abdomen and pelvis is often a key diagnostic step.
• In the elderly, giant cell arteritis and malignancy are more frequent causes.