What is the recommended approach for testing and treating a patient presenting with symptoms suggestive of rheumatoid arthritis?

Testing and Treating Rheumatoid Arthritis

Patients presenting with joint swelling involving more than one joint should be referred to a rheumatologist within 6 weeks of symptom onset, with immediate initiation of diagnostic testing including RF, anti-CCP antibodies, CRP/ESR, complete blood count, comprehensive metabolic panel, and bilateral hand/wrist/foot X-rays. 1, 2

Clinical Assessment for Diagnosis

Identify definite clinical synovitis (joint swelling) in at least one joint not better explained by another disease—this is the cornerstone of RA diagnosis. 3, 1

Key Clinical Features to Document:

• Joint involvement pattern: Symmetric small joint polyarthritis affecting metacarpophalangeal joints, proximal interphalangeal joints, wrists, and metatarsophalangeal joints is characteristic. 1
• Morning stiffness: Duration lasting more than 30 minutes (typically ≥1 hour) before maximal improvement indicates inflammatory arthritis. 1, 4
• Perform a 28-joint count examination: Assess proximal interphalangeal joints, metacarpophalangeal joints, wrists, elbows, shoulders, and knees for both tenderness and swelling. 1
• Squeeze test: Apply pressure across metacarpophalangeal and metatarsophalangeal joints to detect clinical synovitis. 1

Critical pitfall: Distal interphalangeal joints are typically spared in RA—their involvement suggests an alternative diagnosis like psoriatic arthritis or osteoarthritis. 1

Essential Laboratory Testing Panel

Order the following tests simultaneously at initial presentation:

• Rheumatoid factor (RF): Has 70% specificity and moderate sensitivity for RA diagnosis. 1, 5
• Anti-citrullinated protein antibodies (ACPA/anti-CCP): Superior specificity (90%) with 60% sensitivity—order even if RF is positive. 1, 5
• C-reactive protein (CRP): Preferred over ESR as it is more reliable and not age-dependent. 1, 5
• Erythrocyte sedimentation rate (ESR): Obtain at baseline for diagnostic and prognostic purposes. 1, 5
• Complete blood count with differential: Essential to assess for cytopenias before starting treatment. 1
• Comprehensive metabolic panel: Including liver function tests, renal function, glucose, and urate levels. 1
• Urinalysis: Part of standard initial workup. 3, 1

Critical pitfall: Do not delay treatment waiting for positive serology—seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease. 1 Normal CRP/ESR does not exclude RA, as acute phase reactants can be normal even in active disease. 1

Apply the 2010 ACR/EULAR Classification Criteria

A score of ≥6/10 points confirms definite RA diagnosis: 1

Scoring System:

• 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 = 5 points 1
• 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

Imaging Studies

Baseline Imaging:

• Bilateral hand, wrist, and foot X-rays: Obtain at initial presentation to detect erosions, which predict RA diagnosis and disease persistence. 1, 5
• Repeat X-rays at 6 and 12 months: Monitor for radiographic progression. 1

Advanced Imaging When Diagnosis is Uncertain:

• Ultrasound with Power Doppler: Use when clinical examination shows no definite synovitis but suspicion remains high—detects subclinical synovitis 2.18-fold more frequently than clinical examination. 1, 2
• MRI with IV contrast: More sensitive than ultrasound in early stages; detects bone marrow edema (osteitis), which is the best single predictor of future disease progression. 1, 2

Pre-Treatment Screening

Before initiating any biologic therapy or methotrexate, screen for: 1

• Hepatitis B and C: Required before starting biologics
• Tuberculosis: Mandatory screening before biologics
• Vaccination status: Update all routine vaccinations, as immunization may be ineffective during methotrexate therapy 6

Initial Treatment Strategy

First-Line Therapy:

Start methotrexate 15 mg weekly as the anchor drug, with plan to escalate to 20-25 mg weekly. 1, 5 Subcutaneous administration has better bioavailability if oral response is inadequate. 1

• Add short-term low-dose prednisone (10-20 mg daily) as bridge therapy while awaiting DMARD effect. 3, 1
• Intra-articular glucocorticoid injections for localized joint inflammation. 3

Treatment Target:

The primary goal is sustained remission, defined as SDAI ≤3.3, or low disease activity (SDAI ≤11) as an alternative. 1, 5

Monitoring Disease Activity:

• Reassess every 4-6 weeks using composite disease activity measures (SDAI, CDAI, or DAS28). 1, 5
• Repeat CRP/ESR at each visit to monitor inflammatory activity. 1
• Use SDAI when CRP is elevated; CDAI can be used when acute phase reactants are normal. 1

Treatment Escalation:

If inadequate response after 3 months of methotrexate monotherapy, consider triple DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine) or add a biologic agent such as a TNF inhibitor. 1

Methotrexate Monitoring Requirements

• Liver function tests: Perform at baseline and every 4-8 weeks during therapy. 6
• Complete blood count: Monitor at least monthly for cytopenias. 6
• Renal function: Check every 1-2 months. 6

Critical warning: Methotrexate is taken WEEKLY, not daily—mistaken daily use has led to fatal toxicity. 6 Prescriptions should not be written on a PRN basis. 6

Non-Pharmacologic Interventions

• Dynamic exercise programs: Incorporate aerobic exercise and progressive resistance training. 3, 1
• Occupational therapy: For joint protection education, assistive devices, and splinting. 3, 1
• Smoking cessation: Smoking is a modifiable predictor of adverse outcomes. 3, 1
• Weight control and dental care: Address as part of overall patient management. 3

Urgent Referral Criteria

Refer to rheumatology within 6 weeks if: 5, 2

• Small joints of hands or feet are affected
• More than one joint is involved
• Delay of 3 months or longer between symptom onset and seeking medical advice