What are the diagnostic steps and treatment options for arthritis?

Diagnosis of Arthritis

Immediate Referral and Initial Assessment

Any patient presenting with joint swelling (especially polyarticular) associated with pain or stiffness must be referred to a rheumatologist within 6 weeks of symptom onset, as early diagnosis and treatment prevent irreversible joint damage. 1, 2

Key Clinical Features to Identify

• Symmetric small joint involvement (metacarpophalangeal joints, proximal interphalangeal joints, wrists, metatarsophalangeal joints) strongly suggests rheumatoid arthritis 2
• Morning stiffness lasting >30 minutes is characteristic of inflammatory arthritis 2, 3
• Squeeze test positivity of MCPs and MTPs indicates clinical synovitis 2
• Constitutional symptoms (fatigue, low-grade fever) suggest systemic inflammatory disease 3

Critical distinction: Distal interphalangeal joints are typically spared in rheumatoid arthritis but involved in osteoarthritis 2

Diagnostic Workup

Essential Laboratory Tests (Order Immediately)

The minimal laboratory panel must include: 4

• Inflammatory markers: CRP (preferred over ESR as it's more reliable and not age-dependent) 2, 4
• Autoantibodies:
  • Anti-CCP antibodies (90% specificity, 60% sensitivity for RA) 2, 4
  • Rheumatoid factor (70% specificity, similar sensitivity to anti-CCP) 2, 4
• Complete blood count with differential (assess for cytopenias, calculate neutrophil-to-lymphocyte ratio) 2, 4
• Comprehensive metabolic panel (liver function, renal function, glucose) 2, 4
• Urinalysis 2, 4

Conditional testing:

• ANA if diagnosis uncertain or other connective tissue disease suspected 2, 4
• HLA-B27 if spondyloarthropathy suspected (axial symptoms, entheseal involvement) 2, 4

Before initiating biologic therapy, screen for: 2

• Hepatitis B and C
• Tuberculosis (latent TB testing)

Imaging Studies

Baseline imaging is mandatory: 2

1. Plain radiographs (bilateral hands, wrists, feet) to assess for erosions, which predict RA diagnosis and disease persistence 2, 4
2. Ultrasound with Power Doppler is superior to clinical examination for detecting subclinical synovitis when diagnosis is uncertain 1, 2
3. MRI with IV contrast is most sensitive in early stages, detecting bone marrow edema (osteitis), the best single predictor of future disease progression 2

Classification Using 2010 ACR/EULAR Criteria

A score ≥6/10 points confirms definite rheumatoid arthritis: 2, 5

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 2

Serology:

• Negative RF and anti-CCP = 0 points
• Low positive RF or anti-CCP = 2 points
• High positive RF or anti-CCP = 3 points 2

Acute phase reactants:

• Normal CRP and ESR = 0 points
• Abnormal CRP or ESR = 1 point 2

Duration of symptoms:

• <6 weeks = 0 points
• ≥6 weeks = 1 point 2

Critical Pitfalls to Avoid

Do not delay treatment waiting for positive serology—seronegative RA accounts for 20-30% of cases and has similar prognosis. 2 Normal ESR/CRP does not exclude inflammatory arthritis, as acute phase reactants can be normal even in active disease. 2 The 2010 ACR/EULAR criteria assign only 1 point for abnormal inflammatory markers while joint involvement contributes up to 5 points, emphasizing that clinical synovitis trumps laboratory values. 2

Treatment Approach

Immediate Initiation of DMARDs

Patients at risk of persistent arthritis must start DMARDs within 3 months of symptom onset, even if they don't fulfill classification criteria. 1

First-line therapy: 1, 2, 5

• Methotrexate 15-25 mg weekly (the anchor drug, unless contraindicated)
• Short-term low-dose glucocorticoids (10-20 mg prednisone daily for <6 months as bridge therapy while awaiting DMARD effect) 1, 2
• Folic acid supplementation to reduce methotrexate toxicity

Alternative first-line DMARDs if methotrexate contraindicated: 5

• Leflunomide
• Sulfasalazine

Treatment Target and Monitoring

The primary goal is sustained remission or low disease activity. 1, 5

Disease activity assessment every 1-3 months using: 1, 2

• SDAI (Simplified Disease Activity Index): Remission ≤3.3, low disease activity ≤11 2
• CDAI (Clinical Disease Activity Index): Remission ≤2.8, low disease activity ≤10 2
• DAS28: Less stringent, not preferred for defining remission 2

If inadequate response after 3 months or target not reached by 6 months: 2, 5

• Add biologic agent (TNF inhibitor such as infliximab 3 mg/kg IV at 0,2,6 weeks, then every 8 weeks) 6
• OR triple DMARD therapy (methotrexate + sulfasalazine + hydroxychloroquine)

Monitoring Parameters

Repeat at each visit (every 4-6 weeks initially): 2

• 28-joint count examination (PIPs, MCPs, wrists, elbows, shoulders, knees)
• Patient global assessment (0-10 cm scale)
• CRP/ESR

Repeat radiographs at 6 and 12 months to monitor structural damage progression 2

Non-Pharmacologic Interventions

Concurrent with medication: 1, 2

• Dynamic exercise program (aerobic + progressive resistance training)
• Occupational therapy for joint protection education and assistive devices
• Tobacco cessation counseling (smoking predicts worse outcomes)

Differential Diagnosis Considerations

Always exclude: 2

• Psoriatic arthritis (check for psoriatic plaques, nail changes, asymmetric involvement)
• Gout (check uric acid, though normal level doesn't exclude gout)
• Spondyloarthropathies (assess for axial symptoms, enthesitis)
• Systemic lupus erythematosus (if ANA positive)
• Hemochromatosis (if MCP involvement, check iron studies)

For osteoarthritis: Diagnosis is primarily clinical with pain worsening with activity, minimal morning stiffness (<30 minutes), and radiographic evidence of joint space narrowing and osteophytes. 7, 8 Treatment focuses on symptom relief with NSAIDs, weight management, and physical therapy rather than disease modification. 7