What is the recommended approach for diagnosing and treating a patient suspected of having rheumatoid arthritis?

Diagnosing and Treating Rheumatoid Arthritis

Diagnosis

For patients with at least one swollen joint, diagnose rheumatoid arthritis when the 2010 ACR/EULAR classification criteria score reaches ≥6 points, combining joint involvement, serology, acute-phase reactants, and symptom duration—then immediately initiate disease-modifying therapy. 1

Clinical Presentation Requiring Evaluation

• Symmetric polyarthritis affecting hands and feet, with morning stiffness lasting ≥1 hour 1
• Any patient with ≥3 swollen joints, metacarpophalangeal/metatarsophalangeal involvement, or morning stiffness ≥30 minutes warrants urgent rheumatology referral 2
• Refer urgently even with normal inflammatory markers or negative rheumatoid factor if: small joints of hands/feet are affected, more than one joint is involved, or ≥3 months delay exists between symptom onset and seeking care 3, 4

Classification Criteria (2010 ACR/EULAR)

The scoring system requires ≥6 points from four domains 1:

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 including ≥1 small joint = 5 points 1

Serology (at least one test required):

• Negative RF and negative ACPA = 0 points
• Low-positive RF or low-positive ACPA = 2 points
• High-positive RF or high-positive ACPA = 3 points 1, 3

Acute-Phase Reactants:

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

Symptom Duration:

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

Essential Laboratory Testing

Order these tests at baseline for all suspected RA patients:

• Anti-citrullinated protein antibodies (ACPA/anti-CCP): 90% specificity, 60% sensitivity—the most specific test for RA 1, 3, 5
• Rheumatoid factor (RF): 70% specificity, 70-80% sensitivity—less specific than ACPA but still essential 1, 3, 5
• C-reactive protein (CRP): preferred over ESR because it is simpler, more reliable, and not age-dependent 1, 3
• Complete blood count, renal function, and hepatic function for baseline assessment 6

Critical diagnostic pearl: 30-40% of RA patients are RF-negative, so always test ACPA in RF-negative patients with suspected RA 3, 5

Imaging Studies

Initial imaging approach:

• Plain radiographs of hands, wrists, and feet are the first-line imaging modality at baseline 1, 3, 4
• Repeat radiographs within 1 year if disease persists to assess for progression 3
• Ultrasound or MRI should be used when clinical examination is inconclusive or to detect subclinical inflammation and early erosions not visible on plain films 1, 3, 4
• MRI bone edema is a strong independent predictor of subsequent radiographic progression and should be considered for prognostic assessment 1

Early Referral Imperative

Patients with suspected early RA must be seen by rheumatology within 1-2 weeks of referral to capitalize on the "window of opportunity" for preventing structural damage 1, 2, 7

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Treatment

Initiate methotrexate 15 mg weekly immediately upon diagnosis, escalating to 20-25 mg weekly, with a treat-to-target strategy aiming for remission or low disease activity assessed every 4-6 weeks using composite disease activity measures. 3, 4, 7, 8

First-Line Therapy

• Methotrexate is the anchor drug for RA treatment, typically starting at 15 mg weekly and escalating to 20-25 mg weekly 4, 7, 6, 8
• Add folic acid supplementation to reduce methotrexate toxicity 8
• Consider subcutaneous administration if inadequate response to oral methotrexate, as it has superior bioavailability 3
• Continue background methotrexate when adding biologic agents 9

Disease Activity Monitoring

Assess disease activity every 4-6 weeks after treatment initiation using composite measures: 1, 3

• DAS28 (Disease Activity Score-28): recommended by EULAR for assessing disease activity and treatment response 1
• SDAI (Simplified Disease Activity Index) or CDAI (Clinical Disease Activity Index): simpler alternatives that don't require complicated formulas; CDAI doesn't require acute-phase reactants 1
• Monitor patient-reported outcomes including pain, patient global assessment, and Health Assessment Questionnaire Disability Index 1
• Perform 28-joint count examination (proximal interphalangeal joints, metacarpophalangeal joints, wrists, elbows, shoulders, knees bilaterally) 1

Treatment Escalation Algorithm

If target not achieved within 3-6 months, escalate therapy: 3, 7, 8

1. Optimize methotrexate dose to 20-25 mg weekly or switch to subcutaneous administration 3, 4
2. Add or switch to combination DMARD therapy (triple therapy with methotrexate, hydroxychloroquine, sulfasalazine) 3
3. Add biologic DMARD if inadequate response to optimized conventional synthetic DMARDs 7, 6, 8
4. Consider rituximab particularly for seropositive patients (RF and/or anti-CCP positive) 3

Corticosteroid Use

Bridging therapy with corticosteroids:

• Moderate disease: initiate prednisone 10-20 mg/day if inadequately controlled with NSAIDs 3
• Severe disease: initiate prednisone 0.5-1 mg/kg/day and consider adding synthetic or biologic DMARDs immediately 3
• If unable to taper below 10 mg/day after 6-8 weeks, add a DMARD 3
• Intra-articular glucocorticoid injections are appropriate for localized joint inflammation 3

Pre-Treatment Screening

Before initiating biologic agents, screen for:

• Hepatitis B, hepatitis C, and tuberculosis 7, 6
• These infections are contraindications or require special management before starting immunosuppressive therapy 7, 6

Treatment Goals

The primary treatment goal is remission or low disease activity within 6 months to prevent joint destruction, preserve independence, prevent work disability, and reduce cardiovascular and other comorbidities 1, 3

Common Pitfalls to Avoid

• Do not delay DMARD initiation waiting for "definitive" diagnosis—structural damage occurs early, and the window of opportunity is narrow 1, 2, 7
• Do not rely solely on RF—30-40% of RA patients are seronegative, and ACPA provides superior specificity 1, 3, 5
• Do not use NSAIDs or corticosteroids alone as long-term management—they do not prevent joint damage 3, 6
• Do not continue ineffective therapy beyond 3-6 months—rapid escalation improves long-term outcomes 3, 7, 8
• Do not measure both ESR and CRP routinely—CRP alone is sufficient and more reliable 1