What are the diagnostic criteria and treatment options for confirming rheumatoid arthritis (RA)?

Rheumatoid Arthritis Diagnosis and Treatment

Diagnose rheumatoid arthritis using the 2010 ACR/EULAR classification criteria requiring ≥6/10 points based on joint involvement, serology, acute phase reactants, and symptom duration, then immediately initiate methotrexate as first-line therapy targeting remission. 1, 2

Diagnostic Criteria

Clinical Prerequisites

• At least one joint must demonstrate definite clinical synovitis (swelling) that is not better explained by another disease 1, 2
• Symmetric involvement of small joints—particularly metacarpophalangeal (MCP), proximal interphalangeal (PIP), wrists, and metatarsophalangeal (MTP) joints—is characteristic 1
• Distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints are typically spared 1

2010 ACR/EULAR Scoring System (≥6/10 points = definite RA)

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 (at least 1 small joint) = 5 points 1, 2

Serology:

• Negative RF and ACPA = 0 points
• Low positive RF or ACPA = 2 points
• High positive RF or ACPA = 3 points 1

Acute Phase Reactants:

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

Duration of Symptoms:

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

Critical Diagnostic Pitfalls to Avoid

• Do not delay treatment waiting for positive serology—seronegative RA accounts for 20-30% of cases and has similar prognosis 1
• Do not dismiss the diagnosis based on normal ESR/CRP—acute phase reactants are poor predictors and can be normal even in active disease 1
• Negative RF does not exclude RA; anti-citrullinated protein antibody (ACPA) has higher specificity (90%) than RF (70%) 1

Advanced Imaging When Diagnosis is Uncertain

When to Use Imaging

• If the 2010 ACR/EULAR score is <6/10 points, consider advanced imaging to detect subclinical synovitis 1

Imaging Modalities in Order of Preference

Ultrasound:

• Superior to clinical examination for detecting inflammation and structural damage 1
• Power Doppler ultrasound detects synovitis that predicts disease progression 1
• Useful when patients with early arthritis do not meet classification criteria 1

MRI with IV Contrast:

• More sensitive than ultrasound in early stages 1
• Detects bone marrow edema (osteitis), which is the best single predictor of future disease progression and functional deterioration 1

Conventional Radiography:

• Recommended as initial imaging for detecting damage 1
• Baseline bilateral hand, wrist, and foot X-rays are essential for monitoring structural damage progression 1
• Erosions predict RA diagnosis and disease persistence 1

Initial Laboratory Evaluation

• Anti-citrullinated protein antibody (ACPA) testing: high specificity (90%), moderate sensitivity (60%) 1
• Rheumatoid factor (RF) testing: lower specificity (70%), similar sensitivity to ACPA 1
• C-reactive protein (CRP) is preferred over ESR as it's more reliable and not age-dependent 1
• Complete blood count with differential 3
• Hepatic and renal function assessment 3
• Screen for hepatitis B, hepatitis C, and tuberculosis before starting biologic agents 1, 3

Disease Activity Assessment

Clinical Examination

• Perform 28-joint count assessment examining for tenderness and swelling in PIPs, MCPs, wrists, elbows, shoulders, and knees 1
• Include patient-reported outcomes: pain assessment, Patient Global Assessment of Disease Activity, and Health Assessment Questionnaire Disability Index 1
• Include evaluator global assessment by physician, trained nurse, or physician assistant 1

Validated Composite Measures

• Disease Activity Score using 28 joint counts (DAS28) 1, 2
• Simplified Disease Activity Index (SDAI) 1, 2
• Clinical Disease Activity Index (CDAI) 1, 2
• ACR/EULAR remission definition is preferred over DAS28<2.6, which is not sufficiently stringent for determining true clinical remission 2

Treatment Algorithm

First-Line Treatment

• Begin methotrexate immediately after RA diagnosis to prevent disease progression 1, 2
• Methotrexate should be optimized to 20 mg/week by week 8 4
• Short-term glucocorticoids should be considered when initiating methotrexate but tapered as rapidly as clinically feasible 2
• Use methotrexate with caution in patients with hematologic abnormalities or active infections 1

Alternative First-Line Options (if methotrexate contraindicated)

• Leflunomide 2
• Sulfasalazine 2

Treatment Targets

• Primary target is remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) 1, 2
• Monitor disease activity every 1-3 months in active disease 2

Treatment Escalation Strategy

• If no improvement by 3 months or target not reached by 6 months, adjust therapy 2
• Add triple DMARD therapy or add a biologic agent (TNF inhibitor such as adalimumab 40 mg subcutaneously every other week) 1, 4
• Combination methotrexate/biologic therapy is more effective than monotherapy 4

Definition of Difficult-to-Treat RA

All three criteria must be present:

1. Treatment according to EULAR recommendations with failure of ≥2 biologic/targeted synthetic DMARDs with different mechanisms of action after failing conventional synthetic DMARD therapy 5, 2
2. Signs of active/progressive disease (DAS28-ESR >3.2 or CDAI >10, inability to taper glucocorticoids below 7.5 mg/day, or rapid radiographic progression) 5
3. Management perceived as problematic by rheumatologist and/or patient 5

Critical Differential Diagnoses to Exclude

• Psoriatic arthritis 1
• Gout 1
• Hemochromatosis 1