What is the initial workup and screening questions for a middle-aged woman presenting with symptoms of Rheumatoid Arthritis (RA), including laboratory tests and treatment options?

Workup for Rheumatoid Arthritis

For a middle-aged woman with suspected RA, immediately order RF, anti-CCP antibodies, CRP, ESR, CBC with differential, comprehensive metabolic panel, and bilateral hand/wrist/foot X-rays, while simultaneously referring to rheumatology within 6 weeks of symptom onset. 1

Essential Screening Questions

Ask these specific questions to identify clinical synovitis:

• Duration of morning stiffness: Stiffness lasting >30 minutes strongly suggests inflammatory arthritis 1, 2
• Pattern of joint involvement: Ask specifically about symmetric involvement of MCPs, PIPs, wrists, and MTPs 1, 2
• Difficulty making a fist: This indicates functional impairment from synovitis 1
• Duration of symptoms: Symptoms ≥6 weeks contribute 1 point to diagnostic criteria 1
• Family history: RF positivity occurs in ~15% of first-degree relatives of RA patients 1
• Smoking history: Smoking is a modifiable predictor of adverse outcomes 1

Critical pitfall: Do not rely solely on patient-reported "swelling"—you must document definite clinical synovitis (soft, boggy joint swelling) on physical examination, not bony enlargement from osteoarthritis. 1

Physical Examination Priorities

Perform a systematic 28-joint count examination:

• Small joints to examine: PIPs, MCPs, wrists, MTPs for tenderness and swelling 1
• Large joints to examine: Elbows, shoulders, knees 1
• Squeeze test: Compress MCPs and MTPs to assess for clinical synovitis 1
• Joints typically spared: DIPs, first carpometacarpal joints, first MTPs are usually not involved 1

Look for soft tissue swelling (synovitis) rather than hard bony enlargement (osteoarthritis). 1

Laboratory Workup Algorithm

Order these tests immediately at first visit:

Core Autoantibody Panel

• Rheumatoid factor (RF): Sensitivity 60%, specificity 70% 1
• Anti-CCP antibodies (ACPA): Sensitivity 60%, specificity 90%—higher specificity than RF 1, 3
• Both RF and ACPA should be ordered simultaneously—failing to order both reduces diagnostic sensitivity 3

Inflammatory Markers

• CRP (preferred over ESR): More reliable, not age-dependent 1, 3
• ESR: Perform at baseline for diagnostic and prognostic purposes 1, 3

Critical pearl: Normal CRP/ESR does NOT exclude RA—40% of RA patients have normal acute phase reactants even in active disease. 1, 4 Do not dismiss the diagnosis based on normal inflammatory markers. 1

Baseline Laboratory Assessment

• CBC with differential: Assess for cytopenias before starting treatment 1, 5
• Comprehensive metabolic panel: Including liver function, renal function, glucose, urate 1, 5
• Urinalysis: Part of standard initial workup 1, 5

Conditional Testing

• ANA: Only if diagnosis uncertain or screening for other connective tissue diseases like lupus 1, 5
• HLA-B27: Only if spondyloarthropathy suspected (axial or entheseal involvement) 1, 5

Pre-Treatment Screening (if biologics anticipated)

• Hepatitis B, Hepatitis C, tuberculosis screening: Required before starting any biologic therapy 1, 6

Imaging Studies

Baseline radiographs are mandatory:

• Bilateral hand, wrist, and foot X-rays: Obtain at initial presentation to assess for erosions 1, 5
• Erosions predict RA diagnosis and disease persistence 1
• Look for: Periarticular osteopenia, uniform joint space narrowing, marginal erosions 1

Advanced imaging when diagnosis uncertain:

• Ultrasound with Power Doppler: Superior to clinical examination for detecting subclinical synovitis—75% more accurate than physical examination alone 1, 5
• MRI with IV contrast: More sensitive than ultrasound in early disease; detects bone marrow edema (osteitis), which is the best single predictor of future disease progression 1, 5

Use advanced imaging if clinical examination shows no definite synovitis but suspicion remains high. 1

Applying the 2010 ACR/EULAR Classification Criteria

A score ≥6/10 indicates definite RA: 1

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 = 5 points 1

Serology (0-3 points)

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

Important limitation: Seronegative RA accounts for 20-30% of cases and has similar prognosis to seropositive disease. 1 Negative RF does NOT exclude RA. 1

Disease Activity Assessment at Baseline

Calculate baseline disease activity using SDAI (preferred when CRP elevated): 1

SDAI = Tender joint count (0-28) + Swollen joint count (0-28) + Patient global (0-10 cm) + Evaluator global (0-10 cm) + CRP (mg/dL) 1

Target thresholds:

• Remission: SDAI ≤3.3
• Low disease activity: SDAI ≤11
• Moderate: SDAI ≤26
• High: SDAI >26 1

Use CDAI (without CRP) only when acute phase reactants are normal. 1

Monitoring Strategy After Diagnosis

Repeat assessments every 4-6 weeks after treatment initiation:

• Disease activity measures: SDAI or CDAI at each visit 1
• Inflammatory markers: CRP and ESR to monitor treatment response 1
• Radiographs: Repeat hand, wrist, and foot X-rays at 6 and 12 months to monitor radiographic progression 1

Treatment Initiation

Start methotrexate 15 mg weekly immediately as first-line DMARD—do not delay treatment waiting for complete serologic workup. 1, 5

Bridge therapy while awaiting DMARD effect:

• Short-term prednisone 5-10 mg daily 5
• NSAIDs (e.g., naproxen 500 mg twice daily) at minimum effective dose 5

Treatment target: Remission (SDAI ≤3.3) or low disease activity (SDAI ≤11). 1

If inadequate response after 3 months of methotrexate, escalate to triple DMARD therapy or add biologic agent (TNF inhibitor). 1

Critical Pitfalls to Avoid

• Do not delay treatment waiting for positive serology—seronegative RA is common (20-30%) and has similar prognosis 1
• Do not dismiss diagnosis based on normal ESR/CRP—40% of RA patients have normal acute phase reactants 1, 4
• Do not fail to order both RF and ACPA—ordering only one reduces diagnostic sensitivity 3
• Do not rely on laboratory tests as gold standard—clinical synovitis on examination is the cornerstone of diagnosis 1, 4
• Do not delay rheumatology referral beyond 6 weeks—early treatment prevents irreversible joint damage in up to 90% of patients 5