What are the steps to diagnose and treat rheumatoid arthritis in an adult patient?

Clinical Diagnosis of Rheumatoid Arthritis

The diagnosis of rheumatoid arthritis requires at least one joint with definite clinical synovitis not better explained by another disease, followed by application of the 2010 ACR/EULAR classification criteria requiring ≥6/10 points based on joint involvement, serology, acute phase reactants, and symptom duration. 1, 2

Initial Clinical Assessment

Essential Physical Examination Findings

• Perform a 28-joint count examination assessing proximal interphalangeal joints (PIPs), metacarpophalangeal joints (MCPs), wrists, elbows, shoulders, and knees for tenderness and swelling 3, 2
• Look for symmetric involvement of small joints, particularly MCPs, PIPs, wrists, and metatarsophalangeal joints (MTPs) 2
• Use the squeeze test of MCPs and MTPs to assess for clinical synovitis 2
• Document morning stiffness duration—≥60 minutes is the standard threshold, though ≥30 minutes provides optimal discrimination for RA 3
• Note that distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints are typically spared 2

Diagnostic Scoring System

2010 ACR/EULAR Classification Criteria (≥6/10 points required)

Joint Involvement (0-5 points): 1, 2

• 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

Serology (0-3 points): 1, 2

• Negative RF and ACPA = 0 points
• Low positive RF or ACPA = 2 points
• High positive RF or ACPA = 3 points

Acute Phase Reactants (0-1 point): 1, 2

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

Duration of Symptoms (0-1 point): 1, 2

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

Essential Laboratory Workup

First-Line Tests

• Anti-CCP antibodies: 90% specificity, 60% sensitivity—remains highly predictive even when RF is negative 3, 2
• Rheumatoid factor (RF): 70% specificity with similar sensitivity to ACPA—order both simultaneously at initial presentation 3, 2
• C-reactive protein (CRP): Preferred over ESR as it is more reliable, not age-dependent, and CRP ≥5 mg/L associates strongly with morning stiffness and subclinical inflammation 3, 2
• ESR: Measure at baseline for diagnostic and prognostic purposes 2
• Complete blood count with differential: Assess for cytopenias before starting treatment 3, 2
• Comprehensive metabolic panel: Including liver function tests, renal function, glucose, and urate levels 2

Additional Testing When Diagnosis Uncertain

• Antinuclear antibodies (ANA): Screen for other connective tissue diseases like lupus 3, 2
• HLA-B27 typing: Consider if spondyloarthropathy is suspected (axial or entheseal involvement) 3, 2
• Urinalysis: Part of standard initial workup 3, 2

Imaging Studies

Baseline Imaging

• Bilateral hand, wrist, and foot X-rays: Obtain at initial presentation—presence of erosions is highly predictive for RA diagnosis and disease persistence 3, 2
• Look for periarticular osteopenia, uniform joint space narrowing, and osseous erosions 2

Advanced Imaging When Diagnosis Uncertain

• Ultrasound with Power Doppler: Superior to clinical examination for detecting subclinical synovitis and structural damage—can detect inflammation that predicts disease progression even when clinical examination is normal 4, 3, 2
• MRI with IV contrast: More sensitive than ultrasound in early stages—detects bone marrow edema (osteitis), which is the best single predictor of future disease progression and functional deterioration 4, 3, 2
• Consider advanced imaging when clinical examination shows no definite synovitis but suspicion remains high, or when patients with early arthritis do not meet the 2010 ACR/EULAR criteria 4, 2

Critical Diagnostic Pitfalls

• Do not delay treatment waiting for positive serology: Seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease 2
• Do not dismiss the diagnosis based on normal ESR/CRP: Acute phase reactants are poor predictors and can be normal even in active disease—the ACR/EULAR criteria assign only 1 point for abnormal inflammatory markers while joint involvement can contribute up to 5 points 2
• Do not rely solely on laboratory values: Prioritize physical examination findings of definite clinical synovitis over laboratory results 2

Differential Diagnoses to Exclude

• Psoriatic arthritis: Examine skin for psoriatic plaques or nail changes 2
• Gout: Check uric acid levels—normal uric acid effectively excludes gout 2
• Hemochromatosis: Consider in appropriate clinical context 2
• Erosive hand osteoarthritis: Less likely but possible with bilateral hand involvement 2

Treatment Initiation

Immediate Management

• Start methotrexate 15-25 mg weekly as first-line DMARD immediately after diagnosis 1, 5, 6, 7, 8
• Add short-term low-dose glucocorticoids (10-20 mg prednisone daily) as bridge therapy while awaiting DMARD effect—taper as rapidly as clinically feasible 1, 2
• For patients with contraindications to methotrexate, use leflunomide or sulfasalazine as first-line alternatives 1

Treatment Target and Monitoring

• Target sustained remission or low disease activity in every patient 1
• Monitor disease activity every 1-3 months using SDAI (preferred when CRP elevated) or CDAI 1, 3, 2
• If no improvement by 3 months or target not reached by 6 months, adjust therapy by adding triple DMARD therapy or a biologic agent 1, 3, 2
• Repeat hand, wrist, and foot X-rays at 6 months and 12 months to monitor radiographic progression 2

Pre-Treatment Screening

• Screen for hepatitis B, hepatitis C, and tuberculosis before starting any biologic therapy 2, 7, 8