What laboratory tests and treatments are recommended for investigating and managing possible rheumatoid arthritis?

Laboratory Tests for Investigating Rheumatoid Arthritis

The essential laboratory tests for investigating possible rheumatoid arthritis include rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and radiographs of hands and feet. 1, 2

Initial Diagnostic Workup

Core Laboratory Tests

1. Serological Markers:

   • Rheumatoid Factor (RF): Moderate sensitivity (60%) and specificity (70%) 1
   • Anti-Citrullinated Protein Antibodies (ACPA/anti-CCP): High specificity (90%) and moderate sensitivity (60%) 1, 3

2. Inflammatory Markers:

   • Erythrocyte Sedimentation Rate (ESR): Shows diagnostic value for RA development 2
   • C-Reactive Protein (CRP): Preferred over ESR due to simplicity, reliability, and age independence 1

3. Imaging:

   • X-rays of hands, wrists, and feet: Should be performed at baseline and repeated within 1 year 2
   • The presence of erosions is predictive for RA development and disease persistence 2

Additional Laboratory Tests

• Complete Blood Count: To assess for anemia, leukopenia, or thrombocytopenia 2
• Liver Function Tests: To establish baseline before treatment 2
• Renal Function Tests: To establish baseline before treatment 2
• Urinalysis: For exclusion of other diseases 2
• Antinuclear Antibodies (ANA): To help exclude other autoimmune conditions 2

Diagnostic Significance

The 2010 ACR/EULAR classification criteria for RA require a score of ≥6/10 based on:

1. Joint involvement (0-5 points)
2. Serology (0-3 points)
3. Acute phase reactants (0-1 point)
4. Duration of symptoms (0-1 point) 2, 1

For serology, scoring is as follows:

• Negative RF and negative ACPA: 0 points
• Low-positive RF or low-positive ACPA: 2 points
• High-positive RF or high-positive ACPA: 3 points 2

Clinical Pearls and Pitfalls

Important Considerations

• More than 30% of RA patients may have negative RF or ACPA tests 4
• Approximately 40% of RA patients may have normal ESR or CRP 4
• Combined testing of RF and anti-CCP provides higher diagnostic accuracy (89.5%) than either test alone 3

Potential Pitfalls

• False Negatives: Relying solely on laboratory tests can miss early RA cases
• False Positives: RF can be positive in other conditions including infections, other autoimmune diseases, and in elderly patients
• Normal Inflammatory Markers: Normal ESR/CRP does not exclude RA diagnosis

Monitoring Disease Activity

Once diagnosed, regular monitoring should include:

• Tender and swollen joint counts
• Patient's and physician's global assessments
• ESR and CRP every 1-3 months until remission is achieved 2
• Radiographs of hands and feet every 6-12 months during the first few years 2

Treatment Approach

If RA is diagnosed or strongly suspected:

1. First-line Treatment:

   • Methotrexate is considered the anchor drug and should be started at effective doses (12.5-25 mg weekly) with folic acid supplementation 1, 5

2. Treatment Goals:

   • Minimize joint pain and swelling
   • Prevent radiographic damage and visible deformity
   • Maintain work and personal activities
   • Reduce morbidity and mortality 1

3. Treatment Strategy:

   • Implement a treat-to-target approach aiming for remission or low disease activity 1, 5
   • Remission is defined as tender joints, swollen joints, CRP, and patient global assessment all ≤1, or SDAI score ≤3.3 1

4. Inadequate Response:

   • If methotrexate alone is ineffective, consider adding biologic DMARDs such as TNF inhibitors 1, 5

Remember that early aggressive treatment leads to better long-term outcomes and prevention of joint damage 1.