Definition of PUO in Pediatrics
PUO is defined as:
- Fever >38.3°C (101°F) on several occasions
- Lasting >3 weeks
- Unexplained after 1 week of hospital evaluation or 3 outpatient visits
Stepwise Clinical Approach to PUO
STEP 1: Confirm It’s Truly PUO
- Check for fever documentation
- Rule out common infections, partially treated illnesses
- Stop any unnecessary antibiotics or antipyretics
- Ensure detailed history and re-examination is done
STEP 2: Comprehensive History Taking
Ask focused questions about:
- Fever pattern: Intermittent, remittent, continuous, periodic
- Associated symptoms: Rash, joint pain, weight loss, night sweats, GI symptoms
- Exposure history:
- TB contact
- Travel to endemic areas
- Animal contact (cats, dogs, livestock)
- Raw milk intake, unclean water
- Family history: Autoimmune diseases, recurrent fevers
- Drug history: Antiepileptics, antibiotics
- Social clues: School absence, overanxious caregiver (factitious fever)
STEP 3: Detailed Physical Examination
Repeat exams—especially:
- Skin: Rash, petechiae, insect bites
- Lymph nodes: Size, location, tenderness
- Abdomen: Organomegaly
- Joints: Subtle signs of arthritis
- ENT: Sinuses, throat
- Neurologic: Any subtle changes or stiffness
STEP 4: Initial Investigations (Tier 1)
Clue:
- High ferritin + ESR >100 + leukocytosis → Think sJIA
- Pancytopenia → Rule out leukemia, HLH
STEP 5: Second-Line (Tier 2) Workup
If no diagnosis after Tier 1:
- Abdomen USG / CT scan
- ANA, dsDNA, RF (autoimmune screening)
- LDH, uric acid (malignancy)
- Bone marrow aspiration (if pancytopenia or suspicion of leukemia)
- Echocardiography (if Kawasaki or endocarditis suspected)
- Serology (EBV, CMV, HIV, Bartonella)
STEP 6: Advanced Investigations (Tier 3)
For unresolved PUO:
- PET-CT / Gallium scan
- Lymph node or liver biopsy
- Genetic testing (if periodic fever syndrome suspected)
- Immunodeficiency workup (IgA, IgG, IgM, CD markers)
- Cytokine panel (if HLH or MAS suspected)
STEP 7: Trial Therapy – Caution Advised
- Avoid empirical antibiotics/steroids unless child is toxic
- Can consider:
- Anti-TB trial in endemic areas if strong clinical suspicion
- Steroid trial only after ruling out infection/malignancy
When to Refer to Specialist
- Unresolved PUO beyond 3 weeks of structured evaluation
- Suspected malignancy, autoimmune disease, or immunodeficiency
- Recurrent PUO (multiple episodes per year)
- Psychosocial concerns (e.g., Munchausen by proxy)
Key Points to Remember
- Don’t rush—70% of PUO cases resolve with time or basic workup
- History and serial physical exams are more powerful than random tests
- Think beyond infections—autoimmune and malignancies are common in PUO
- Use a tiered approach to minimize unnecessary tests and costs
