What is the appropriate workup and treatment for a patient presenting with joint pain and suspected rheumatoid arthritis (RA) versus osteoarthritis (OA)?

Workup for Rheumatoid Arthritis versus Osteoarthritis

Distinguishing Clinical Features

The cornerstone of differentiating RA from OA is identifying inflammatory synovitis—soft tissue swelling around joints with morning stiffness lasting >30 minutes—versus the bony enlargement and mechanical pain pattern of OA. 1

Key Clinical Differences

Rheumatoid Arthritis:

• Symmetric involvement of small joints (MCPs, PIPs, wrists, MTPs) with DIP joints typically spared 1
• Morning stiffness duration >30 minutes, often lasting hours 1, 2
• Soft tissue swelling (synovitis) on examination, not bony enlargement 1
• Systemic symptoms may be present (fatigue, low-grade fever) 2
• Squeeze test of MCPs and MTPs elicits tenderness 1

Osteoarthritis:

• Asymmetric involvement, commonly affecting DIPs, first CMC joints, first MTP joints, knees, hips 1
• Morning stiffness <30 minutes, typically resolves quickly 3
• Bony enlargement (Heberden's/Bouchard's nodes), crepitus 3
• No systemic symptoms 3
• Pain worsens with activity, improves with rest 4

Essential Laboratory Workup

For Suspected Rheumatoid Arthritis

Order the following tests immediately when RA is suspected:

• Anti-CCP antibodies: High specificity (90%) with moderate sensitivity (60%), superior to RF for diagnosis 1, 5
• Rheumatoid factor (RF): Lower specificity (70%) with similar sensitivity to anti-CCP; both should be ordered simultaneously 1, 5
• CRP: Preferred over ESR as it's more reliable and not age-dependent 1
• ESR: Measure at baseline for diagnostic and prognostic purposes 1
• Complete blood count with differential: Assess for cytopenias before starting treatment 1
• Comprehensive metabolic panel: Including liver function, renal function, glucose, urate 1
• Urinalysis: Part of standard initial workup 1

Critical Pearl: Do not dismiss RA diagnosis based on negative RF or normal inflammatory markers—seronegative RA accounts for 20-30% of cases, and ESR/CRP can be normal even in active disease 1, 2

For Suspected Osteoarthritis

Laboratory testing is minimal for OA:

• No specific diagnostic blood tests exist for OA 3
• Consider inflammatory markers (CRP, ESR) only to exclude inflammatory arthritis if diagnosis is uncertain 3
• Uric acid level if gout is in the differential 1

Imaging Studies

Rheumatoid Arthritis

Obtain bilateral hand, wrist, and foot X-rays at baseline:

• Look for periarticular osteopenia, uniform joint space narrowing, and erosions 1, 5
• Erosions on baseline radiographs are highly predictive for RA diagnosis and disease persistence 1, 5
• Repeat X-rays at 6 and 12 months to monitor radiographic progression 1

Advanced imaging when diagnosis is uncertain:

• Ultrasound with Power Doppler: Superior to clinical examination for detecting subclinical synovitis and predicts disease progression 1, 5
• MRI with IV contrast: Most sensitive in early stages; detects bone marrow edema (osteitis), the best single predictor of future disease progression 1, 5

Osteoarthritis

Plain radiographs of affected joints:

• Look for joint space narrowing, osteophytes, subchondral sclerosis, subchondral cysts 3
• Radiographic changes may not correlate with symptom severity 3

Diagnostic Criteria for Rheumatoid Arthritis

Apply the 2010 ACR/EULAR Classification Criteria (score ≥6/10 needed for definite RA): 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 = 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

Treatment Approach

Rheumatoid Arthritis

Start methotrexate 15 mg weekly immediately upon diagnosis—do not delay treatment waiting for complete serologic workup, as early treatment prevents irreversible joint damage. 1, 6, 2

Initial treatment strategy:

• Escalate methotrexate rapidly to 20-25 mg weekly within a few weeks 6
• Add short-term low-dose prednisone (≤10 mg/day) as bridge therapy while awaiting DMARD effect 1, 6
• Supplement with folic acid to reduce methotrexate toxicity 6

Treatment target:

• Remission (SDAI ≤3.3 or CDAI ≤2.8) or low disease activity (SDAI ≤11 or CDAI ≤10) 1, 6
• Assess disease activity every 1-3 months during active disease 6, 2
• Aim for >50% improvement within 3 months; target must be attained within 6 months 6

Escalation if inadequate response:

• Add biologic DMARD (TNF inhibitor first-line) or JAK inhibitor to methotrexate after 3-6 months of inadequate response 6
• For patients with poor prognostic factors (high RF/anti-CCP, erosions, elevated CRP), consider combination therapy from the start 6

Pre-treatment screening:

• Screen for hepatitis B, hepatitis C, and tuberculosis before starting biologic agents 1, 7

Osteoarthritis

Non-pharmacologic interventions are first-line:

• Education about disease course and self-management 8
• Physical activity and exercise (aerobic, strength training, aquatic) with uniform positive effects on pain 8, 6
• Weight management if overweight, particularly for knee/hip OA 8
• Orthotics (knee sleeves, hand splints, orthopedic shoes) show small but consistent positive effects 8

Pharmacologic management:

• Acetaminophen or NSAIDs for pain control 9, 4
• Ibuprofen 1200-3200 mg daily in divided doses (400-800 mg tid or qid) for OA 9
• Use lowest effective dose for shortest duration; administer with meals if GI complaints occur 9

Psychological interventions:

• CBT, psychosocial interventions, and relaxation techniques show uniform positive effects on pain in OA 8

Critical Pitfalls to Avoid

For Rheumatoid Arthritis:

• Never delay DMARD initiation waiting for positive serology or complete workup—irreversible joint damage occurs early 1, 6
• Never dismiss RA diagnosis based solely on negative RF or normal ESR/CRP 1
• Never use NSAIDs or corticosteroids alone—they provide only symptomatic relief without disease modification 6, 4
• Never undertreat patients with poor prognostic factors (erosions, high RF/anti-CCP, elevated CRP)—they require aggressive combination therapy from the start 6
• Refer urgently to rheumatology within 6 weeks of symptom onset if inflammatory arthritis is suspected 1, 5

For Osteoarthritis:

• Do not order extensive autoimmune workup unless clinical features suggest inflammatory arthritis 3
• Do not rely solely on radiographic findings—symptom severity may not correlate with X-ray changes 3