What are the clinical features of rheumatoid arthritis (RA) and how should it be evaluated?

Clinical Features and Evaluation of Rheumatoid Arthritis

Cardinal Clinical Features

Rheumatoid arthritis presents with symmetric polyarthritis affecting multiple joints, particularly the hands and feet, accompanied by morning stiffness lasting ≥1 hour. 1, 2

Joint Involvement Pattern

• Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and wrist joints are the most commonly affected sites, showing swelling, tenderness, and limited range of motion 2, 3
• Metatarsophalangeal (MTP) joints are also preferentially involved, along with knees, ankles, elbows, and shoulders 1, 3
• Distal interphalangeal (DIP) joints, first carpometacarpal joints, and first metatarsophalangeal joints are typically spared, helping distinguish RA from osteoarthritis 3
• Symmetry is the hallmark of joint involvement in RA 1, 3, 4

Characteristic Symptoms

• Morning stiffness lasting ≥1 hour (often up to several hours) is a cardinal symptom that differentiates RA from osteoarthritis, where stiffness typically lasts <30 minutes 1, 2, 5
• Joint swelling presents as soft, boggy swelling from synovial inflammation (not bony enlargement) 2, 3
• Tenderness on palpation with severe motion impairment, even before radiologic bone damage appears 2, 5
• Improvement with NSAIDs or corticosteroids (but not opioids) suggests inflammatory arthritis 2

Extra-Articular Manifestations

• Subcutaneous rheumatoid nodules are characteristic of more severe disease 1, 2
• Interstitial lung disease, vasculitis, and inflammatory eye disease mark severe disease with worse prognosis 1, 2
• Systemic symptoms including fatigue, low-grade fever, weight loss, and malaise are common 5

Diagnostic Evaluation

Physical Examination

Perform a 28-joint count examination assessing PIPs, MCPs, wrists, elbows, shoulders, and knees for both tenderness and swelling 2, 3, 6

• Squeeze test of MCPs and MTPs: lateral compression eliciting pain indicates active synovitis 2, 6
• Look for definite clinical synovitis (soft tissue swelling) in at least one joint not better explained by another disease—this is the cornerstone of RA diagnosis 3, 6
• Document morning stiffness duration and number/pattern of involved joints 2, 3
• Examine for rheumatoid nodules, particularly over extensor surfaces and pressure points 2, 5

Laboratory Assessment

Order rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA/anti-CCP) simultaneously at initial presentation, as these are the cornerstone autoantibody tests for RA diagnosis and prognosis 1, 3, 6

• ACPA has 90% specificity with 60% sensitivity; RF has 70% specificity with similar sensitivity 3, 6
• Negative RF and ACPA do not exclude RA—seronegative RA accounts for 20-30% of cases 1, 3
• Measure CRP (preferred over ESR) at baseline for diagnostic and prognostic purposes; CRP is more reliable and not age-dependent 1, 3, 6
• ESR should also be measured at baseline as it contributes to classification criteria 1, 3
• Complete blood count with differential to assess for cytopenias before starting DMARDs 3, 6
• Comprehensive metabolic panel including liver function, renal function, glucose, and urate levels 3, 6
• Urinalysis as part of standard initial workup 1, 3, 6

Additional Testing When Diagnosis Uncertain

• Antinuclear antibodies (ANA) to screen for other connective tissue diseases like lupus 1, 3
• HLA-B27 typing if spondyloarthropathy is suspected (axial or entheseal involvement) 1, 3

Imaging Studies

Obtain bilateral hand, wrist, and foot X-rays at initial presentation to detect periarticular osteopenia, uniform joint space narrowing, and erosions 1, 3, 6

• Baseline erosions are highly predictive of RA diagnosis and persistent disease 1, 3, 6
• Radiographic hallmarks include periarticular osteopenia, uniform joint space narrowing, and marginal erosions 3, 4, 7
• Repeat X-rays at 6 months and 12 months to monitor radiographic progression 3, 6

Advanced Imaging When Clinical Examination Is Equivocal

• Ultrasound with Power Doppler is superior to clinical examination for detecting inflammation and structural damage, improving detection of subclinical synovitis by ~75% 1, 2, 3, 6
• MRI with IV contrast is more sensitive than ultrasound in early disease, detecting bone marrow edema (osteitis) which is the best single predictor of future disease progression and functional deterioration 1, 2, 3, 6
• Consider advanced imaging when patients do not meet 2010 ACR/EULAR criteria but clinical suspicion remains high 1, 3

Disease Activity Assessment

Calculate the Simplified Disease Activity Index (SDAI) using tender joint count (0-28), swollen joint count (0-28), patient global assessment (0-10 cm), evaluator global assessment (0-10 cm), and CRP (mg/dL) 3, 6

• SDAI thresholds: remission ≤3.3, low disease activity ≤11, moderate ≤26, high >26 3, 6
• SDAI is preferred over CDAI when CRP is elevated, as it incorporates the inflammatory marker 3, 6
• Clinical Disease Activity Index (CDAI) may be used when acute-phase reactants are normal 3, 6

2010 ACR/EULAR Classification Criteria

A score of ≥6/10 points is needed for definite RA classification, based on: 3

• 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 3
• Serology: negative RF and ACPA = 0 points, low positive RF or ACPA = 2 points, high positive RF or ACPA = 3 points 3
• Acute phase reactants: normal CRP and ESR = 0 points, abnormal CRP or ESR = 1 point 3
• Duration of symptoms: <6 weeks = 0 points, ≥6 weeks = 1 point 3

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive serology—seronegative RA is common and has similar prognosis 3
• Do not dismiss the diagnosis based on normal ESR/CRP—acute phase reactants can be normal even in active disease 3
• Do not rely solely on clinical examination—imaging studies may reveal subclinical inflammation 2
• Early RA may present with only a few affected joints, making diagnosis challenging 2
• Refer patients with joint swelling in ≥2 joints to rheumatology within 6 weeks of symptom onset, as early treatment prevents irreversible joint damage 3, 6

Prognostic Features

• Patients with positive RF are >70% likely to develop joint erosions within 2 years of disease onset 4
• Radiological joint damage develops rapidly during the first years after disease onset and assumes a slower rate after 9 years 8, 9
• Persistently elevated CRP at diagnosis predicts severe disease with high risk of progressive joint erosions and functional deterioration 3
• Extra-articular manifestations indicate more severe disease with shortened life expectancy by 3-5 years 1