What is the diagnostic approach and treatment for inflammatory arthritis?

Diagnostic Approach to Inflammatory Arthritis

Begin with joint examination to identify definite clinical synovitis (swelling on palpation, not just tenderness) in at least one joint that cannot be explained by another disease—this is the essential first step before pursuing any laboratory or imaging studies. 1

Initial Clinical Assessment

Perform a focused examination targeting specific joints and patterns:

• Examine metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, wrists, and metatarsophalangeal (MTP) joints bilaterally for symmetric swelling and tenderness—these are the characteristic sites for rheumatoid arthritis 2, 1
• Perform a squeeze test across MCPs and MTPs to assess for clinical synovitis 1
• Document morning stiffness duration—stiffness lasting ≥1 hour before maximal improvement strongly suggests inflammatory arthritis 2, 3
• Note that distal interphalangeal joints are typically spared in rheumatoid arthritis, which helps differentiate from osteoarthritis 1

Critical pitfall: Do not rely solely on patient-reported joint pain or tenderness—you must document objective joint swelling on examination to establish synovitis 1

Laboratory Workup

Once clinical synovitis is confirmed, obtain the following tests in this order:

First-Line Serologic Tests

• Anti-citrullinated protein antibody (ACPA): 90% specificity with 60% sensitivity—the most specific test for rheumatoid arthritis 2, 1
• Rheumatoid factor (RF): 70% specificity with 60-80% sensitivity—less specific than ACPA but still valuable 2, 1
• C-reactive protein (CRP): Preferred over ESR because it correlates more closely with disease activity and is not age-dependent 1, 4
• Erythrocyte sedimentation rate (ESR): Obtain for baseline assessment 2, 1

Additional Essential Tests

• Complete blood count with differential to assess for cytopenias 1
• Comprehensive metabolic panel including liver function, renal function, glucose, and urate levels 1
• Antinuclear antibodies (ANA) if diagnosis is uncertain to screen for other connective tissue diseases 1, 4

Critical pitfall: Do not dismiss inflammatory arthritis based on normal CRP or ESR—acute phase reactants can be normal even in active disease and are poor predictors of rheumatoid arthritis 1

Critical pitfall: Do not exclude rheumatoid arthritis based on negative RF—seronegative rheumatoid arthritis accounts for 20-30% of cases and has similar prognosis to seropositive disease 1

Apply the 2010 ACR/EULAR Classification Criteria

Calculate the diagnostic score using four domains (≥6 points confirms definite rheumatoid arthritis) 2, 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 (≤3× upper limit of normal) = 2 points
• High positive RF or ACPA (>3× upper limit of normal) = 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

Imaging Studies

Initial Imaging

Obtain bilateral hand, wrist, and foot X-rays at baseline to assess for erosions and establish a baseline for monitoring structural damage progression 2, 1

• Radiographic findings include periarticular osteopenia, uniform joint space narrowing, and osseous erosions 2
• Erosions predict rheumatoid arthritis diagnosis and disease persistence 1

Advanced Imaging (When Indicated)

If the classification score is <6 points but clinical suspicion remains high, proceed with ultrasound or MRI to detect subclinical synovitis 2, 1:

• Ultrasound with power Doppler is superior to clinical examination for detecting synovitis and can identify active inflammation that predicts disease progression 2, 1
• MRI with IV contrast is more sensitive than ultrasound in early stages and can detect bone marrow edema (osteitis), which is the best single predictor of future disease progression and functional deterioration 2, 1

When to Refer to Rheumatology

Refer immediately to rheumatology if any of the following are present 2:

• Grade ≥2 inflammatory arthritis (moderate symptoms with functional impairment in instrumental activities of daily living) 2
• Symptoms persisting >6 weeks 2
• Any patient requiring >20 mg prednisone daily that cannot be tapered to <10 mg/day within 4 weeks 2

Rationale for urgent referral: Erosive, irreversible joint damage can occur within weeks of symptom onset, making early rheumatology involvement critical to determine if disease-modifying therapy beyond steroids is required 2

Treatment Initiation

Immediate Treatment Strategy

Start methotrexate 15-25 mg weekly as first-line disease-modifying antirheumatic drug (DMARD) immediately upon diagnosis 1, 5, 6:

• Add prednisone 10-20 mg daily as bridging therapy for rapid symptom control while awaiting DMARD effect 2, 1
• Plan to taper prednisone as methotrexate takes effect (typically 6-12 weeks) 2

Pre-Treatment Screening

Before initiating any biologic therapy, screen for hepatitis B, hepatitis C, and tuberculosis 1, 5, 6—this is mandated by FDA labeling for biologic agents 7

Treatment Target and Monitoring

The primary treatment target is remission, defined as Simplified Disease Activity Index (SDAI) ≤3.3 or Clinical Disease Activity Index (CDAI) ≤2.8 1:

• Reassess disease activity every 4-6 weeks using composite measures (SDAI or CDAI) 1
• If inadequate response after 3 months of methotrexate monotherapy, add a biologic agent (TNF inhibitor preferred as first biologic) or consider triple DMARD therapy (methotrexate + hydroxychloroquine + sulfasalazine) 1

Critical pitfall: Do not use DAS28 alone for treatment decisions when CRP is markedly elevated—SDAI provides a more stringent definition of disease activity 1

Escalation Strategy

If inadequate response to first TNF inhibitor, switch to an alternative mechanism such as rituximab, abatacept, or tocilizumab (IL-6 receptor inhibitor) 1:

• Do not combine biologic agents—concomitant use of TNF blockers with anakinra or abatacept increases infection risk without added benefit 7
• Avoid live vaccines during biologic therapy 7

Special Considerations for High-Risk Disease

Patients with high-positive RF (>3× upper limit of normal) or high-positive ACPA require aggressive therapy from the outset 1:

• These patients have 1.48-fold increased risk of extra-articular manifestations including interstitial lung disease, vasculitis, and inflammatory eye disease 8
• Life expectancy is shortened by 3-5 years, particularly with extra-articular disease 2, 8
• Monitor closely for pulmonary, cardiovascular, ophthalmologic complications 8

Monitoring Radiographic Progression

Repeat hand, wrist, and foot X-rays at 6 months and 12 months to monitor for radiographic progression 1:

• Presence of new erosions indicates inadequate disease control and necessitates treatment escalation 1
• Do not delay treatment escalation waiting for radiographic changes—bone marrow edema on MRI predicts erosions before they appear on X-rays 2