What is the diagnostic approach for a middle-aged woman with suspected rheumatoid arthritis?

Diagnostic Approach to Rheumatoid Arthritis

The diagnosis of rheumatoid arthritis requires identifying at least one joint with definite clinical synovitis not explained by another disease, followed by application of the 2010 ACR/EULAR classification criteria scoring system, with advanced imaging (ultrasound or MRI) reserved for cases where clinical examination is equivocal. 1

Clinical Assessment

Essential Physical Examination Findings

• Examine for symmetric synovitis (joint swelling) in small joints, particularly metacarpophalangeal joints, proximal interphalangeal joints, wrists, and metatarsophalangeal joints 1
• Perform a 28-joint count assessment examining PIPs, MCPs, wrists, elbows, shoulders, and knees for both tenderness and swelling 1
• Squeeze test of MCPs and MTPs helps identify clinical synovitis, a cornerstone finding 1
• Document morning stiffness duration >30 minutes and difficulty making a fist, which are characteristic symptoms 1
• Note that distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints are typically spared 1

Apply the 2010 ACR/EULAR Classification Criteria

A score of ≥6/10 points establishes definite RA. 1 The scoring system includes:

• Joint involvement: 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 = 5 points 1
• Serology: Negative RF and ACPA = 0 points, low positive RF or ACPA = 2 points, high positive RF or ACPA = 3 points 1
• Acute phase reactants: Normal CRP and ESR = 0 points, abnormal CRP or ESR = 1 point 1
• Symptom duration: <6 weeks = 0 points, ≥6 weeks = 1 point 1

Laboratory Workup

First-Line Essential Tests

• Order RF and anti-CCP (ACPA) simultaneously at initial presentation - these are cornerstone autoantibody tests 1
• Anti-CCP has high specificity (90%) with moderate sensitivity (60%), while RF has lower specificity (70%) with similar sensitivity 1
• CRP is preferred over ESR as it is more reliable and not age-dependent 1
• Complete blood count with differential to assess for cytopenias before starting treatment 1
• Comprehensive metabolic panel including liver function tests, renal function, glucose, and urate levels 1
• Urinalysis as part of standard initial workup 1

Critical Pitfall to Avoid

Do not delay treatment or dismiss the diagnosis based on negative serology or normal inflammatory markers. 1 Seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease 1. Acute phase reactants can be normal even in active disease 1.

Conditional Testing

• ANA testing if diagnosis remains uncertain or to screen for other connective tissue diseases like lupus 1
• HLA-B27 typing if spondyloarthropathy is suspected (axial or entheseal involvement) 1
• Hepatitis B, Hepatitis C, and tuberculosis screening before starting any biologic therapy 1, 2

Imaging Studies

Baseline Radiography

• Obtain bilateral hand, wrist, and foot X-rays at initial presentation 1
• Conventional radiography shows periarticular osteopenia, uniform joint space narrowing, and osseous erosions 3, 4
• The presence of erosions on baseline radiographs is highly predictive for RA diagnosis and disease persistence 1
• Repeat X-rays at 6 months and 12 months to monitor radiographic progression 1

Advanced Imaging When Diagnosis is Uncertain

When clinical examination shows no definite synovitis but suspicion remains high, ultrasound or MRI should be used to detect subclinical inflammation. 3, 1

• Ultrasound with Power Doppler is superior to clinical examination for detecting inflammation and structural damage 3, 1
• Ultrasound can detect synovitis that predicts disease progression even when clinical examination is normal 3, 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 1, 4
• MRI synovitis can be present even in clinical remission and predicts subsequent joint damage 3, 4

Imaging in Undifferentiated Inflammatory Arthritis

• The presence of bone marrow edema or both synovitis and erosion on MRI increases likelihood of developing RA (positive likelihood ratio 4.5 and 4.8, respectively) 3
• Power Doppler ultrasound significantly improves prediction of progression to RA when combined with clinical prediction rules 3
• MRI flexor tenosynovitis is a predictor of early RA (sensitivity 0.60, specificity 0.73) 3

Diagnostic Algorithm

1. Identify definite clinical synovitis in at least one joint not explained by another condition 1
2. Apply the 2010 ACR/EULAR criteria scoring system 1
3. If score ≥6/10, diagnose as definite RA 1
4. If score <6/10 but clinical suspicion remains high, obtain ultrasound with Power Doppler or MRI to detect subclinical synovitis 3, 1
5. Order baseline bilateral hand, wrist, and foot X-rays regardless of classification score to establish baseline for monitoring 1

Key Differential Diagnoses to Exclude

• Psoriatic arthritis - examine skin for psoriatic plaques or nail changes; unlike RA, may show "pencil-in-cup" deformities and predilection for distal interphalangeal joints 1, 4
• Gout - normal uric acid effectively excludes gout as primary diagnosis 1
• Hemochromatosis - should be excluded in appropriate clinical context 1
• Spondyloarthropathies - axial involvement is uncommon in RA 4

Timing and Referral

Refer to rheumatology within 6 weeks of symptom onset if inflammatory arthritis is suspected, as early treatment prevents irreversible joint damage 1. The window of therapeutic opportunity in early RA makes prompt diagnosis essential 5, 6.