Diagnosis of Rheumatoid Arthritis
Rheumatoid arthritis is diagnosed primarily through clinical assessment using the 2010 ACR/EULAR classification criteria, requiring a score of ≥6/10 points based on joint involvement, serology (RF and anti-CCP antibodies), acute phase reactants (CRP/ESR), and symptom duration, with imaging reserved for cases of diagnostic uncertainty. 1
Clinical Presentation and Initial Assessment
The diagnosis begins with identifying at least one joint with definite clinical synovitis (swelling) that is not better explained by another disease—this is the fundamental entry criterion. 1, 2
Key Clinical Features to Identify:
- Symmetric involvement of small joints, particularly metacarpophalangeal (MCP), proximal interphalangeal (PIP), wrists, and metatarsophalangeal (MTP) joints is characteristic. 1, 3
- Morning stiffness lasting ≥1 hour before maximal improvement is a typical sign related to disease activity. 3, 2
- Large joints (shoulders, elbows, hips, knees, ankles) may also be affected. 1
- Distal interphalangeal joints are typically spared—their involvement should prompt consideration of alternative diagnoses like psoriatic arthritis. 1
Physical Examination Specifics:
- Perform a 28-joint count assessment examining PIPs, MCPs, wrists, elbows, shoulders, and knees for tenderness and swelling. 1, 4
- Squeeze test of MCPs and MTPs helps assess for clinical synovitis. 1
- Examine skin for psoriatic plaques or nail changes to exclude psoriatic arthritis. 1
The 2010 ACR/EULAR Classification Criteria (Score-Based Algorithm)
A score of ≥6/10 points is required for definite RA classification. 1 Calculate points as follows:
Joint Involvement (0-5 points):
- 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 (at least 1 small joint) = 5 points 1
Serology (0-3 points):
- Negative RF and anti-CCP = 0 points
- Low positive RF or anti-CCP (≤3× upper limit of normal) = 2 points
- High positive RF or anti-CCP (>3× upper limit of normal) = 3 points 1
Acute Phase Reactants (0-1 point):
- Normal CRP and ESR = 0 points
- Abnormal CRP or ESR = 1 point 1
Duration of Symptoms (0-1 point):
- <6 weeks = 0 points
- ≥6 weeks = 1 point 1
Essential Laboratory Testing
First-Line Serologic Tests:
- Anti-CCP antibodies (ACPA): High specificity (90%) with moderate sensitivity (60%)—the most specific test for RA. 1, 2
- Rheumatoid factor (RF): Lower specificity (70%) with similar sensitivity to anti-CCP. 1, 2
- Important caveat: Seronegative RA accounts for 20-30% of cases, so negative RF does not exclude RA. 1, 2
Inflammatory Markers:
- C-reactive protein (CRP) is preferred over ESR as it is more reliable and not age-dependent. 1, 4
- Critical pitfall: Acute phase reactants can be normal even in active disease—do not dismiss the diagnosis based on normal ESR/CRP. 1
Additional Baseline Testing:
- Complete blood count with differential to assess for cytopenias. 1, 4
- Comprehensive metabolic panel including liver and renal function. 1
- Urinalysis as part of standard workup. 1, 4
- ANA testing if diagnosis is uncertain to screen for other connective tissue diseases. 1, 4
- HLA-B27 if spondyloarthropathy is being considered. 1, 4
Pre-Treatment Screening (if RA confirmed):
Imaging in Diagnosis
When Clinical Criteria Are Sufficient:
If the patient scores ≥6/10 on the ACR/EULAR criteria with clear clinical synovitis, imaging is not required for diagnosis but should be obtained for baseline monitoring. 1
When There Is Diagnostic Doubt:
When diagnostic uncertainty exists, conventional radiography, ultrasound, or MRI can improve diagnostic certainty above clinical criteria alone (strength of recommendation 9.1/10). 6
Imaging Modality Selection:
- Conventional radiographs of hands and feet should be the initial imaging technique, though sensitivity for early structural damage is low. 6
- Ultrasound with Power Doppler is superior to clinical examination for detecting inflammation (2.18-fold better detection) and can identify subclinical synovitis when diagnosis is uncertain. 6, 4
- MRI is more sensitive than ultrasound in early stages, detecting bone marrow edema (osteitis) which is the strongest predictor of future disease progression. 6, 4
- MRI or ultrasound can predict progression from undifferentiated inflammatory arthritis to clinical RA (strength of recommendation 7.9/10). 6
Baseline Imaging for Monitoring:
- Bilateral hand, wrist, and foot X-rays are essential at baseline to monitor structural damage progression, even if diagnosis is already established. 1
Diagnostic Algorithm
Identify clinical synovitis in at least one joint not explained by another condition. 1, 2
Apply the 2010 ACR/EULAR criteria and calculate the score (0-10 points). 1
If score ≥6/10: Diagnose as definite RA and proceed with baseline imaging and treatment planning. 1
If score <6/10 but clinical suspicion remains high: Consider advanced imaging (ultrasound with Power Doppler or MRI) to detect subclinical synovitis. 6, 1
If imaging shows inflammation: This increases diagnostic certainty and predicts progression to RA. 6
If still uncertain: Follow-up evaluation as patients may develop additional features over time. 1
Critical Pitfalls to Avoid
- Do not delay treatment waiting for positive serology—seronegative RA is common (20-30% of cases) and has similar prognosis to seropositive disease. 1
- Do not dismiss the diagnosis based on normal ESR/CRP—inflammatory markers are poor predictors and can be normal even in active disease. 1
- Do not rely solely on laboratory values—RA is primarily a clinical diagnosis, and the ACR/EULAR criteria assign only 1 point for abnormal inflammatory markers versus up to 5 points for joint involvement. 1
- Do not overlook the importance of early diagnosis—prompt treatment with disease-modifying antirheumatic drugs within the first 6 weeks prevents irreversible joint damage. 1, 2, 5