What is the initial laboratory workup for a patient presenting with arthralgia (joint pain)?

Initial Laboratory Workup for Arthralgia

The initial laboratory workup for a patient presenting with arthralgia should include a complete autoimmune panel with antinuclear antibodies (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and inflammatory markers (ESR and CRP). 1

Core Laboratory Tests

• Essential baseline tests:

  • Complete blood count (CBC) with differential
  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)
  • Rheumatoid factor (RF)
  • Anti-cyclic citrullinated peptide antibodies (anti-CCP/ACPA)
  • Antinuclear antibodies (ANA)
  • Renal and hepatic function tests

• Additional tests based on clinical suspicion:

  • HLA-B27 (if symptoms suggest reactive arthritis or spinal involvement) 2
  • Uric acid (if gout is suspected)
  • Joint fluid analysis (if septic or crystal arthritis is suspected) 2

Diagnostic Value of Serological Tests

Test	Sensitivity	Specificity	Clinical Significance
Anti-CCP	67-78.5%	95-98%	Highest specificity for RA, strong predictor of arthritis development [1,3]
RF	69-84%	78-85%	Higher sensitivity but lower specificity for RA [1]
ANA	Lower	Lower	More relevant for other autoimmune conditions [1]

Imaging Studies to Consider

• Plain radiographs: To exclude metastases and evaluate joint damage (erosions) 2
• Ultrasound or MRI: If clinical suspicion warrants, especially for:
  • Persistent arthritis unresponsive to treatment
  • Suspicion of differential diagnoses (metastatic lesions, septic arthritis)
  • Detection of subclinical inflammation 2, 4

Risk Stratification

The presence of positive serological markers significantly impacts risk assessment:

• ACPA positivity is the strongest predictor of progression to clinical arthritis (HR = 6.0) 3
• High ACPA levels further increase risk (HR = 1.7) 3
• Combined ACPA and RF positivity increases risk compared to ACPA alone (HR = 3.0) 3

Clinical Pearls and Pitfalls

• Pearl: Early detection of autoantibodies, particularly anti-CCP, can identify patients at high risk for developing rheumatoid arthritis before clinical arthritis appears 5, 3
• Pitfall: Relying solely on RF without testing for anti-CCP may miss early RA cases, as anti-CCP has higher specificity 1
• Pearl: Subclinical inflammation on MRI is present in 44% of patients with clinically suspect arthralgia and can help predict progression 4
• Pitfall: Normal inflammatory markers do not rule out inflammatory arthritis, particularly in early disease

When to Consider Rheumatology Referral

• Positive autoantibodies (RF or anti-CCP)
• Persistent joint symptoms with elevated inflammatory markers
• Joint swelling (synovitis)
• Symptoms persisting beyond 6 weeks 2

The laboratory workup should be guided by the clinical presentation and suspicion for specific rheumatologic conditions, with the understanding that early identification of high-risk patients allows for timely intervention that may prevent disease progression.