What are the diagnostic tests and treatment options for rheumatoid arthritis?

Diagnostic Testing for Rheumatoid Arthritis

For any patient with joint swelling involving more than one joint, refer to a rheumatologist within 6 weeks of symptom onset and initiate diagnostic testing immediately, as early treatment prevents irreversible joint damage. 1, 2

Clinical Examination Findings That Trigger Testing

• Joint swelling (not bony enlargement) in at least one joint that cannot be explained by trauma or another disease is the key trigger for RA testing. 2
• Symmetric involvement of small joints—particularly metacarpophalangeal (MCP), proximal interphalangeal (PIP), wrists, and metatarsophalangeal (MTP) joints—strongly suggests RA. 2
• A positive "squeeze test" of MCPs and MTPs indicates clinical synovitis and warrants immediate laboratory evaluation. 1, 2
• Morning stiffness lasting more than 30 minutes is characteristic. 1
• Distal interphalangeal joints are typically spared in RA, which helps differentiate it from osteoarthritis. 2

Essential First-Line Laboratory Tests

Order these tests immediately for any patient with suspected inflammatory arthritis:

• Rheumatoid Factor (RF): Present in 80% of RA patients, but has lower specificity (70%) than anti-CCP. 3, 4
• Anti-Cyclic Citrullinated Peptide (anti-CCP) antibodies: This is the most specific test (90% specificity) with 60% sensitivity—order this even if RF is negative, as 20-30% of RA patients are seronegative. 2, 3
• C-Reactive Protein (CRP): Preferred over ESR because it is more reliable and not age-dependent. 2, 3
• Erythrocyte Sedimentation Rate (ESR): Use as a complementary inflammatory marker. 3
• Complete Blood Count (CBC) with differential: To assess for cytopenias before starting treatment. 1, 2
• Comprehensive Metabolic Panel: Including liver function tests (transaminases), renal function, glucose, and urate levels—essential before initiating methotrexate. 2, 3
• Urinalysis: Part of standard initial workup. 1, 2

Additional Tests to Exclude Other Diagnoses

• Antinuclear Antibodies (ANA): Order if diagnosis is uncertain to screen for other connective tissue diseases like lupus. 1, 2
• HLA-B27: Consider only if spondyloarthropathy is suspected (axial symptoms, enthesitis). 2
• Hepatitis B, Hepatitis C, and Tuberculosis screening: Required before starting any biologic DMARD therapy. 2, 5

Imaging Studies

Obtain baseline imaging at diagnosis to document structural damage and monitor progression:

• Bilateral hand, wrist, and foot X-rays: Essential at baseline to detect erosions, which predict persistent disease and guide treatment intensity. 2, 3
• Repeat X-rays at 6 and 12 months to monitor radiographic progression. 2
• Ultrasound with Power Doppler: Superior to clinical examination for detecting subclinical synovitis when diagnosis is uncertain—can detect inflammation that predicts disease progression. 1, 2
• MRI with IV contrast: Most sensitive in early disease for detecting bone marrow edema (osteitis), which is the best single predictor of future joint destruction. 2

Diagnostic Scoring System (2010 ACR/EULAR Criteria)

A score of ≥6/10 points confirms definite RA: 2, 6

Joint Involvement (0-5 points):

• 1 large joint = 0 points
• 2-10 large joints = 1 point
• 1-3 small joints = 2 points
• 4-10 small joints = 3 points

• 10 joints (at least 1 small joint) = 5 points 2

Serology (0-3 points):

• Negative RF and anti-CCP = 0 points
• Low positive RF or anti-CCP (≤3× upper limit of normal) = 2 points
• High positive RF or anti-CCP (>3× upper limit of normal) = 3 points 2

Acute Phase Reactants (0-1 point):

• Normal CRP and ESR = 0 points
• Abnormal CRP or ESR = 1 point 2

Duration of Symptoms (0-1 point):

• <6 weeks = 0 points
• ≥6 weeks = 1 point 2

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive serology—20-30% of RA patients are seronegative, and they have similar prognosis to seropositive patients. 2
• Do not dismiss RA based on normal CRP/ESR—inflammatory markers can be normal even in active disease and are poor predictors of RA. 2
• Do not rely solely on RF—it is present in many other conditions and 15% of healthy first-degree relatives of RA patients. 2, 3
• Always order anti-CCP in RF-negative patients—30-40% of RA patients may be RF-negative but anti-CCP positive. 3

Treatment Initiation Based on Test Results

Start treatment immediately upon diagnosis—do not wait for complete test results if clinical synovitis is present: 6

• Methotrexate 15-25 mg weekly is the first-line DMARD and should be started as soon as RA is diagnosed. 2, 6, 5, 7
• Short-term low-dose prednisone (10-20 mg daily) as bridge therapy while awaiting DMARD effect. 2, 6
• Target remission or low disease activity using composite measures (SDAI ≤3.3 for remission, ≤11 for low disease activity). 2, 6
• Reassess disease activity every 4-6 weeks using validated composite measures (SDAI, CDAI, or DAS28). 2, 3, 6
• If inadequate response after 3 months of methotrexate, add a biologic agent (TNF inhibitor) or switch to triple DMARD therapy. 2, 6

Monitoring After Diagnosis

• Repeat CRP/ESR every 4-6 weeks after treatment initiation to monitor response. 2, 3
• Liver function tests every 4-8 weeks while on methotrexate. 8
• CBC with differential regularly to monitor for methotrexate-induced cytopenias. 8
• Repeat hand/wrist/foot X-rays at 6 and 12 months to assess for radiographic progression. 2, 3