What is the recommended initial workup for a 45-year-old male presenting with fever and arthralgias?

Initial Workup for a 45-Year-Old Male with Fever and Arthralgias

The recommended initial workup for a 45-year-old male with fever and arthralgias should include complete blood count, inflammatory markers, autoimmune serology, and joint imaging, with special consideration for Adult-Onset Still's Disease in the differential diagnosis.

Key Initial Laboratory Tests

• Complete Blood Count (CBC):

  • Look for neutrophilic leukocytosis, which is typical in inflammatory conditions like Adult-Onset Still's Disease (AOSD) 1
  • Check for anemia (common in chronic inflammatory conditions)
  • Assess platelet count (thrombocytosis in inflammation, thrombocytopenia may suggest other etiologies) 1

• Inflammatory Markers:

  • Erythrocyte Sedimentation Rate (ESR)
  • C-Reactive Protein (CRP)
  • Ferritin levels (markedly elevated in AOSD) 1

• Liver Function Tests:

  • Transaminases (AST, ALT)
  • Alkaline phosphatase
  • Bilirubin 1

• Autoimmune Serology:

  • Rheumatoid Factor (RF)
  • Anti-Cyclic Citrullinated Peptide (anti-CCP) antibodies
  • Antinuclear Antibodies (ANA)
  • HLA-B27 (especially if axial symptoms are present) 1

Imaging Studies

• Plain Radiographs:

  • X-rays of affected joints to assess for erosions or other abnormalities 1
  • Chest X-ray (recommended for all patients with fever) 1

• Ultrasound:

  • Consider joint ultrasound to detect synovitis if available 1

Microbiological Tests

• Blood Cultures:

  • At least two sets from different sites 1
  • If central venous catheter is present, paired central and peripheral cultures 1

• Specific Infectious Disease Testing (based on exposure history):

  • Consider testing for brucellosis, Q fever if relevant exposure history 1
  • HIV testing if risk factors present 1

Additional Considerations

Adult-Onset Still's Disease (AOSD) Evaluation

AOSD should be strongly considered in the differential diagnosis as it classically presents with:

• Fever (typically ≥39°C, spiking pattern)
• Arthralgia/arthritis (commonly affecting knees, wrists, and ankles)
• Characteristic salmon-pink rash (often coinciding with fever spikes)
• Markedly elevated ferritin 1

Malignancy Screening

Consider malignancy screening if there are concerning features such as:

• Weight loss
• Night sweats
• Persistent symptoms despite treatment 2, 3

Rheumatological Referral

Early referral to a rheumatologist is recommended if:

• Symptoms persist beyond 2 weeks
• Inflammatory markers are significantly elevated
• There is evidence of synovitis 1

Diagnostic Algorithm

1. Initial Assessment:

   • Document fever pattern (continuous vs. intermittent/spiking)
   • Map joint involvement (symmetric vs. asymmetric, large vs. small joints)
   • Note any associated symptoms (rash, sore throat, weight loss)

2. First-line Testing:

   • CBC, ESR, CRP, ferritin
   • Liver function tests
   • Blood cultures
   • Chest X-ray
   • Joint X-rays of affected areas

3. Second-line Testing (based on initial results):

   • Autoimmune serology (RF, anti-CCP, ANA)
   • Joint ultrasound if synovitis suspected
   • Consider CT imaging if source remains unclear after initial workup 1

4. Specialized Testing (if indicated):

   • Bone marrow examination if hematologic abnormalities persist 2
   • Synovial fluid analysis if effusion present 1
   • HLA-B27 if axial spondyloarthropathy suspected 1

Common Pitfalls to Avoid

• Misattribution to viral syndrome: Persistent fever and arthralgia beyond 1-2 weeks warrants thorough investigation
• Missing AOSD diagnosis: Consider this diagnosis in patients with high fevers, joint pain, and markedly elevated ferritin, even in the absence of rash
• Overlooking malignancy: Acute leukemia can present with arthralgia, fever and cytopenias, mimicking rheumatologic disease 2
• Neglecting travel history: Certain infections like brucellosis or arboviral diseases can present with persistent arthralgia 1, 4
• Focusing only on joints: Systemic symptoms may indicate underlying conditions requiring different management approaches

Early and accurate diagnosis is crucial as conditions like AOSD may require prompt initiation of corticosteroids or other immunomodulatory therapy to prevent complications and improve outcomes 1.