Fever of Unknown Origin in Animals

Definition of FUO: A persistent or recurrent fever that does not resolve spontaneously or with empirical antibiotics, and for which the cause remains hidden after initial history, physical examination, and basic testing.
Body Temperature Regulation:
- The Hypothalamus: Acts as the body's thermostat, receiving input from thermoreceptors to adjust heat production and loss.

- Fever vs. Hyperthermia:
  - Fever: A regulated increase in body temperature where the hypothalamic set point is raised (typically 39.5°–41.1°C).
  - Hyperthermia: An unregulated increase (e.g., heatstroke, seizures) where the set point remains normal but heat gain exceeds heat loss.
Pathogenesis of Fever: Triggered by exogenous pyrogens (drugs, toxins, endotoxins) which cause inflammatory cells to release endogenous pyrogens (cytokines). This leads to the synthesis of prostaglandin E in the hypothalamus, raising the set point.

Dogs: Most common causes are noninfectious inflammatory disease (including immune-mediated), followed by infectious disease and neoplasia.
Cats: Primarily caused by infectious diseases, with Feline Infectious Peritonitis (FIP) being a noteworthy cause.
Horses & Farm Animals: Most often caused by infectious or inflammatory diseases such as pneumonia, peritonitis, abscesses, or endocarditis.

Stage 1 (Initial screening):
- Thorough history and physical examination (including ophthalmic and neurologic).
- CBC (with blood smear and fibrinogen), serum biochemistry, and urinalysis with culture.
- FeLV/FIV testing for cats and thoracic/abdominal radiography.
Stage 2 (Focused testing):
- Bacteriologic blood culture and abdominal ultrasonography.
- Arthrocentesis (crucial for dogs, as immune-mediated polyarthritis is common) and lymph node/organ aspirates.
- Serology and molecular tests (PCR).

Stage 3 (Advanced investigation):
- Advanced imaging (CT/MRI) and cerebrospinal fluid (CSF) analysis.
- Bone marrow evaluation (indicated for unexplained CBC abnormalities).
- Biopsies, laparoscopy, or exploratory surgery.

Supportive Care:
- IV Fluid Therapy: Beneficial for dehydration.
- Antipyretics: NSAIDs (e.g., aspirin, carprofen, flunixin meglumine) can help lower regulated temperatures.
- Cooling Warning: External cooling is not recommended for true fever, as it works against the body's internal regulatory mechanisms.
Trial Treatment:
- Considered when a diagnosis is not reached or testing is discontinued.
- Should be based on a tentative diagnosis with defined success criteria.
- Caution: Trial treatments can interfere with further diagnostic investigations.