What investigations are recommended for evaluating a patient with suspected rheumatoid arthritis?

Investigations for Suspected Rheumatoid Arthritis

Order anti-citrullinated protein antibodies (ACPA/anti-CCP) and rheumatoid factor (RF) as your primary serologic tests, along with C-reactive protein (CRP) and baseline X-rays of hands, wrists, and feet—these form the core diagnostic workup for suspected RA. 1, 2

Essential Laboratory Tests

Serologic Markers

• Test both RF and ACPA (anti-CCP) in all patients presenting with synovitis, as these are the cornerstone autoantibodies for RA diagnosis 3, 1
• ACPA has superior specificity (90%) with moderate sensitivity (60%), making it particularly valuable for confirming the diagnosis 3
• RF has comparable sensitivity (60-80%) but lower specificity (70%), increasing to approximately 80% with prolonged disease 3
• Negative RF and ACPA do not exclude RA—30-40% of RA patients are seronegative 2, 4
• High-positive RF or high-positive ACPA scores 3 points in the 2010 ACR/EULAR classification criteria, while low-positive results score 2 points 3

Acute Phase Reactants

• Measure CRP at baseline for both diagnosis and prognosis 3, 1
• CRP is preferred over ESR because it is simpler, more reliable, and not age-dependent 3
• Measuring both CRP and ESR offers no additional clinical value 3
• Abnormal CRP or ESR scores 1 point in the classification criteria 3
• Note that 40% of RA patients have normal acute phase reactants, so normal values do not exclude the diagnosis 4

Imaging Studies

Plain Radiography

• Obtain X-rays of hands, wrists, and feet at baseline as the initial imaging method of choice 3, 1
• The presence of erosions is predictive for RA development and disease persistence, scoring 5 points in classification criteria if erosions are present 3
• Repeat X-rays within 1 year to assess progression 3
• Early radiographic features include soft tissue swelling and juxtaarticular osteoporosis 5

Advanced Imaging (When Indicated)

• MRI of hands and wrists can be considered when RA is suspected but clinical findings are inconclusive 3, 1
• MRI can identify synovitis, bone edema, and erosions not evident on clinical examination or plain films 3
• Ultrasound can detect synovial thickening even within finger joints, improving early assessment 5
• Routine use of MRI and ultrasound is not recommended due to insufficient evidence for diagnosis or prognosis in undifferentiated arthritis 3

Clinical Assessment Components

Joint Examination

• Perform a 28-joint count including proximal interphalangeal joints (1st-5th), metacarpophalangeal joints (1st-5th), wrists, elbows, shoulders, and knees bilaterally 3
• Document the number of tender and swollen joints systematically 3
• Small joint involvement (1-3 joints) scores 2 points, 4-10 small joints scores 3 points, and >10 joints including at least 1 small joint scores 5 points 3

Patient-Reported Outcomes

• Assess morning stiffness duration (>30 minutes suggests inflammatory arthritis) 3
• Measure pain using visual analog scales 3
• Obtain patient Global Assessment of Disease Activity score 3
• Evaluate functional status with Health Assessment Questionnaire Disability Index 3

Additional Baseline Tests

• Complete blood count with differential to assess for anemia and other hematologic abnormalities 6
• Renal and hepatic function tests before initiating disease-modifying therapy 6
• Consider HLA-B27 testing only in specific clinical settings if axial or entheseal involvement suggests spondyloarthropathy rather than RA 3

Critical Pitfalls to Avoid

• Do not delay referral to rheumatology based on negative RF or normal acute phase reactants—refer urgently if small joints of hands/feet are affected, multiple joints are involved, or symptoms persist ≥3 months 1, 2, 7
• Do not routinely perform synovial biopsy; reserve this for persistent monoarthritis when differential diagnosis is unclear 3
• Do not order genetic testing routinely, as no genetic test can be recommended for standard RA diagnosis 3
• Remember that distal interphalangeal joints, sacroiliac joints, and lumbar spine are rarely involved in RA—their involvement suggests alternative diagnoses 5

Scoring for Classification

A score of ≥6/10 on the 2010 ACR/EULAR criteria establishes definite RA classification in patients with at least one joint showing definite clinical synovitis not better explained by another disease 3. The scoring includes:

• Joint involvement (0-5 points based on number and size of joints)
• Serology (0-3 points for RF and ACPA results)
• Acute phase reactants (0-1 point for abnormal CRP or ESR)
• Symptom duration (1 point if ≥6 weeks) 3