What tests are used to diagnose Rheumatoid Arthritis (RA)?

Diagnostic Tests for Rheumatoid Arthritis

The diagnosis of RA requires clinical assessment combined with serological testing (rheumatoid factor and anti-CCP antibodies), inflammatory markers (ESR and CRP), and imaging studies, with conventional radiography of hands and feet as the initial imaging modality, supplemented by ultrasound or MRI when diagnostic doubt exists. 1, 2, 3

Clinical Assessment Foundation

• A complete rheumatologic history and thorough physical examination of all peripheral joints for tenderness, swelling, and range of motion must be performed 1
• Pay particular attention to symmetric involvement of small joints (metacarpophalangeal, proximal interphalangeal, wrist joints), morning stiffness lasting at least 1 hour, and the number/pattern of tender or swollen joints 1, 4
• The diagnosis requires at least one joint with definite clinical synovitis that is not better explained by another disease 5, 3

Essential Serological Tests

Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA/anti-CCP) are the two critical autoantibodies that must be tested for suspected RA. 1, 6, 3

• IgM rheumatoid factor by enzyme-linked immunosorbent assay has the strongest association with RA diagnosis 7
• Anti-CCP antibodies are highly specific for RA and are the strongest predictor when combined with clinical features (OR 13.8) 5
• The combination of IgM-RF, anti-CCP, and latex test provides the most powerful discrimination between RA and non-RA patients 7
• A caveat: MRI synovitis was found to be more valuable than anti-CCP determination in the absence of rheumatoid factor, highlighting that imaging can sometimes outperform serology 5

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be performed to assess inflammation 1, 6
• C-reactive protein is strictly correlated with clinical assessment and radiographic changes, making it particularly useful for monitoring 4
• Complete blood count with differential should be performed to evaluate for infection, inflammation, or malignancy 1

Imaging Studies: A Hierarchical Approach

Conventional radiography (CR) of the hands and feet should be used as the initial imaging technique to detect damage. 5, 1

When to Add Advanced Imaging

When there is diagnostic doubt, CR, ultrasound or MRI can be used to improve the certainty of a diagnosis of RA above clinical criteria alone (strength of recommendation 9.1/10). 5

• Ultrasound and MRI are superior to clinical examination in detecting joint inflammation, with detection rates 2.18-fold and 2.20-fold higher respectively for synovitis in hands/wrists 5, 1
• Ultrasound or MRI should be considered if conventional radiographs do not show damage, as they can detect damage at an earlier time point, especially in early RA 5
• The absence of fluid on ultrasound essentially excludes inflammatory arthritis 8

Prognostic Imaging Features

• MRI bone edema is a strong independent predictor of subsequent radiographic progression in early RA and should be considered for prognostic assessment 5, 1
• The presence of bone edema or both synovitis and erosion on MRI increases the likelihood of developing RA (positive likelihood ratio 4.5 and 4.8, respectively) 5
• Ultrasound power Doppler activity, when combined with clinical prediction rules, significantly improves prediction of progression to RA (AUC 0.905 to 0.962) 5

Additional Laboratory Investigations

• Antinuclear antibody (ANA) testing should be performed if connective tissue disease is suspected as a differential diagnosis 1
• Patients being considered for biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis before starting immunosuppressive therapy 1, 3

Joint Fluid Analysis When Indicated

• Arthrocentesis should be performed if septic arthritis or crystal-induced arthritis is suspected 1
• Synovial fluid analysis should include cell count with differential, crystal analysis, and Gram stain with culture 1
• Image-guided aspiration is essential when fluid collections are detected, as imaging alone cannot distinguish infected from non-infected collections 8

Common Pitfalls to Avoid

• Do not rely solely on conventional radiography in early disease, as its sensitivity for structural damage in RA diagnosis is low and disease activity cannot be assessed 5
• Do not dismiss the diagnosis based on negative RF alone—up to 30% of RA patients may be seronegative, and imaging findings may be more valuable in this context 5
• Do not assume clinical remission means true remission—power Doppler activity has been found in 15-62% of patients in clinical remission by DAS28 criteria, and MRI synovitis is present in 96% of such patients 1

Algorithmic Approach

1. Start with clinical assessment focusing on symmetric small joint involvement and morning stiffness
2. Order serological tests (RF and anti-CCP) plus inflammatory markers (ESR, CRP) and CBC
3. Obtain baseline conventional radiographs of hands and feet
4. Add ultrasound or MRI if diagnostic doubt persists or radiographs are negative despite clinical suspicion
5. Consider joint aspiration if monoarticular presentation or concern for septic/crystal arthritis
6. Screen for infections (hepatitis B/C, tuberculosis) before initiating immunosuppressive therapy