What labs are used to diagnose rheumatoid arthritis?

Laboratory Tests for Diagnosing Rheumatoid Arthritis

The essential laboratory tests for diagnosing rheumatoid arthritis include anti-citrullinated protein antibodies (ACPA/anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), with anti-CCP having the highest specificity at 95-98%. 1

Core Diagnostic Laboratory Tests

Serological Markers

1. Anti-citrullinated protein antibodies (ACPA/anti-CCP)

   • Sensitivity: 67-78.5%
   • Specificity: 95-98% (highest specificity)
   • Included in 2010 ACR/EULAR classification criteria
   • Superior alternative to RF in laboratory diagnostics 2
   • Predictive of disease development and progression 3

2. Rheumatoid Factor (RF)

   • Sensitivity: 69-84%
   • Specificity: 78-85% (lower than anti-CCP)
   • Present in approximately 70-80% of RA patients
   • Specificity increases with higher titers 3
   • Can be positive in other conditions (less specific) 4

Inflammatory Markers

1. C-reactive protein (CRP)

   • Acute phase reactant
   • More reliable and not age-dependent
   • Better predictor of RA when levels are higher 3
   • Correlates with clinical assessment and radiographic changes 5

2. Erythrocyte sedimentation rate (ESR)

   • Traditional inflammatory marker
   • Shows some diagnostic value for RA development
   • Less specific than CRP 3

Diagnostic Algorithm

1. Initial Laboratory Panel

   • Anti-CCP antibodies
   • Rheumatoid factor
   • CRP (preferred over ESR) 3
   • Complete blood count with differential
   • Renal and hepatic function tests 6

2. Interpretation of Results

   • Positive anti-CCP + positive RF: Highest specificity for RA (>90%)
   • Positive anti-CCP + negative RF: Still highly suggestive of RA
   • Negative anti-CCP + positive RF: Consider other diagnoses
   • Negative anti-CCP + negative RF: Does not rule out RA (30-40% of RA patients may be seronegative) 4

3. Additional Testing When Indicated

   • Antinuclear antibodies (ANA): If suspecting overlap with other connective tissue disorders
   • HLA typing (HLA-B27): If suspecting spondyloarthropathies 3
   • X-rays of hands and feet: To assess for early erosions

Clinical Correlation

Laboratory results must be interpreted in the context of clinical findings:

• Joint involvement pattern: Small joints of hands and feet, symmetric distribution
• Symptom duration: Morning stiffness lasting >1 hour
• Physical examination: Tender and swollen joints, particularly MCPs, PIPs, wrists 5

Important Considerations

• Combined testing improves accuracy: The combination of RF and anti-CCP has a sensitivity of 90.2%, specificity of 83.3%, and accuracy of 89.5% 7

• Seronegative RA: More than 30% of patients with RA may have negative tests for RF or anti-CCP antibodies 4

• Normal inflammatory markers: Up to 40% of patients with RA may have normal ESR or CRP, especially early in disease 4

• Early referral: Patients with suspected RA should be referred to a rheumatologist within 6 weeks of symptom onset for definitive diagnosis 1

Monitoring Disease Activity

Once diagnosed, disease activity should be monitored using:

• CRP (preferred) or ESR
• Validated composite measures:
  • Disease Activity Score (DAS28)
  • Simplified Disease Activity Index (SDAI)
  • Clinical Disease Activity Index (CDAI) 3

Common Pitfalls to Avoid

• Relying solely on laboratory tests without clinical correlation
• Dismissing RA diagnosis in seronegative patients
• Failing to repeat inflammatory markers when clinically indicated
• Delaying referral to rheumatology while waiting for positive serology
• Not considering other diagnoses with similar presentations (psoriatic arthritis, gout) 1

Remember that according to the 2010 ACR/EULAR classification criteria, a score of ≥6/10 is required for definite RA diagnosis, based on joint involvement pattern, serology, acute phase reactants, and symptom duration 1.