What is the diagnostic approach for a patient presenting with joint pain and swelling suspected of having rheumatoid arthritis?

Diagnostic Approach for Rheumatoid Arthritis

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

Initial Clinical Assessment

Key Clinical Features to Identify

• Joint swelling (synovitis) is the cornerstone finding - look specifically for soft tissue swelling around joints, not bony enlargement. 1, 2
• Perform the squeeze test on metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints - tenderness suggests inflammatory arthritis. 1, 2
• Morning stiffness lasting >30 minutes is characteristic and distinguishes inflammatory from mechanical joint disease. 1, 3
• Document the pattern of joint involvement: symmetric small joint polyarthritis (MCPs, proximal interphalangeal joints, wrists, MTPs) is most typical. 2, 3
• Note that distal interphalangeal joints are typically spared in RA - involvement suggests alternative diagnoses like psoriatic arthritis or osteoarthritis. 2

Physical Examination Specifics

• Conduct a 28-joint count examination assessing PIPs, MCPs, wrists, elbows, shoulders, and knees for both tenderness and swelling. 2
• Examine skin for psoriatic plaques or nail changes to exclude psoriatic arthritis. 2
• Check for rheumatoid nodules, though these are typically late findings. 3

Essential Laboratory Testing

First-Line Serologic Tests (Order Simultaneously)

• Anti-citrullinated protein antibodies (ACPA/anti-CCP): 90% specificity, 60% sensitivity - the most specific test for RA. 2, 4, 5
• Rheumatoid factor (RF): 70% specificity with similar sensitivity to ACPA - order both tests together as they provide complementary information. 2, 4
• C-reactive protein (CRP): preferred over ESR as it is more reliable and not age-dependent. 2, 6
• Erythrocyte sedimentation rate (ESR): measure at baseline for diagnostic and prognostic purposes. 2

Critical pitfall: Do not delay treatment waiting for positive serology - seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease. 2, 4

Critical pitfall: Do not dismiss the diagnosis based on normal ESR/CRP - acute phase reactants can be normal even in active inflammatory disease. 2, 4

Additional Baseline Laboratory Tests

• Complete blood count with differential to assess for cytopenias before starting treatment. 2, 5
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels. 2
• Urinalysis as part of standard initial workup. 1, 2
• Antinuclear antibodies (ANA) if diagnosis remains uncertain to screen for other connective tissue diseases like lupus. 1, 2
• HLA-B27 only if spondyloarthropathy is suspected (axial or entheseal involvement). 2

Pre-Treatment Screening (If Biologic Therapy Anticipated)

• Hepatitis B, Hepatitis C, and tuberculosis screening before starting any biologic therapy. 2, 5

Imaging Studies

Baseline Radiography

• Obtain bilateral hand, wrist, and foot X-rays at initial presentation - the presence of erosions is highly predictive for RA diagnosis and disease persistence. 2, 4
• Radiographic hallmarks include periarticular osteopenia, uniform joint space narrowing, and osseous erosions. 2
• Repeat X-rays at 6 months and 12 months to monitor radiographic progression. 2

Advanced Imaging (When Diagnosis Uncertain)

• Ultrasound with Power Doppler is superior to clinical examination for detecting subclinical synovitis and predicts disease progression. 2, 4
• MRI with IV contrast is more sensitive than ultrasound in early stages and detects bone marrow edema (osteitis), which is the best single predictor of future disease progression and functional deterioration. 2, 4
• Use advanced imaging when clinical examination shows no definite synovitis but suspicion remains high, or when patients do not meet the 2010 ACR/EULAR criteria. 2

Applying the 2010 ACR/EULAR Classification Criteria

A score of ≥6/10 points is needed for definite RA classification. 2, 7 Calculate points as follows:

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, 7

Serology (0-3 points)

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

Important caveat: Patients with erosive disease typical of RA with compatible history should be classified as having RA regardless of score. 7

Critical Differential Diagnoses to Exclude

• Psoriatic arthritis: can present with polyarticular involvement, elevated CRP, and negative RF - examine for skin/nail changes. 2
• Gout: check uric acid levels, though normal uric acid does not completely exclude gout. 2
• Hemochromatosis: consider if atypical features present. 2
• Polymyalgia rheumatica: especially in elderly patients with polymyalgic-like onset. 3

Algorithmic Diagnostic Pathway

1. Identify definite clinical synovitis in at least one joint not better explained by another disease. 2, 7
2. Order complete laboratory panel (RF, ACPA, CRP, ESR, CBC, CMP, urinalysis) and baseline X-rays (bilateral hands, wrists, feet). 2, 4
3. Calculate 2010 ACR/EULAR score:
   • If score ≥6/10: Diagnose as definite RA and refer urgently to rheumatology. 2, 7
   • If score <6/10 but clinical suspicion high: Consider ultrasound with Power Doppler or MRI to detect subclinical synovitis. 2, 4
4. If imaging shows synovitis: Treat as early RA even if criteria not fully met. 2
5. If imaging negative but symptoms persist: Schedule follow-up evaluation as patients may develop additional features over time. 2

Timing and Urgency

• Refer to rheumatology within 6 weeks of symptom onset - multiple studies show better outcomes when treatment starts earlier. 1, 4
• Initiate methotrexate immediately if ACPA or RF is positive with clinical synovitis and elevated inflammatory markers. 4
• Treatment should begin immediately after RA diagnosis to prevent disease progression. 7