What is the initial approach to diagnosing and treating a patient presenting with joint pain?

Differential Diagnosis for Joint Pain

The initial approach to joint pain requires determining whether the pain is monoarticular, oligoarticular, or polyarticular, followed by distinguishing inflammatory from non-inflammatory causes through clinical features, laboratory testing, and plain radiography as the first-line imaging modality. 1, 2

Clinical Assessment Framework

Pattern Recognition by Joint Distribution

Polyarticular involvement (≥4 joints):

• Suspect rheumatoid arthritis if metacarpophalangeal (MCP) or metatarsophalangeal (MTP) joints are swollen 2
• Positive "squeeze test" (pain with compression of MCP or MTP joints) strongly indicates inflammatory arthritis 2
• Morning stiffness >30 minutes supports inflammatory rather than mechanical causes 2

Oligoarticular involvement (2-3 joints):

• Consider seronegative spondyloarthropathy, particularly if enthesitis or axial symptoms present 1
• Evaluate for crystal arthropathy (gout, pseudogout) 1

Monoarticular involvement:

• Rule out septic arthritis first through joint aspiration if effusion present 3
• Consider crystal arthropathy, trauma, or early inflammatory disease 1, 3

Inflammatory vs. Non-Inflammatory Differentiation

Inflammatory features:

• Palpable synovitis (warm, swollen joints) 2
• Morning stiffness >30 minutes 2
• Improvement with activity 2
• Elevated ESR or CRP 2

Non-inflammatory features:

• Pain worsens with activity 3
• Brief morning stiffness (<30 minutes) 3
• Bony enlargement without warmth 2

Essential Laboratory Workup

For polyarticular joint pain, order the following initial panel: 2

• Complete blood count (CBC) to exclude non-rheumatologic diseases and assess systemic involvement 2
• Urinalysis and transaminases to exclude non-rheumatologic diseases 2
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) to quantify inflammation and predict persistent/erosive disease 2
• Rheumatoid factor (RF) interpreted as negative (≤14-15 IU/mL), low positive (>ULN but ≤3× ULN), or high positive (>3× ULN) 2
• Anti-cyclic citrullinated peptide (anti-CCP) antibodies, as both RF and anti-CCP positivity predict severe disease and poor prognosis 2
• Antinuclear antibodies (ANA) to identify systemic lupus erythematosus and other connective tissue diseases 2

Critical caveat: Infections (mononucleosis, cytomegalovirus, parvovirus), other autoimmune diseases (Sjögren's syndrome, systemic lupus, systemic sclerosis), and vasculitis can cause false positive RF; always interpret RF in conjunction with anti-CCP and clinical findings 2

Imaging Algorithm

Initial Imaging

Plain radiographs of the affected joints are the initial imaging method of choice for all suspected inflammatory arthritis: 1, 2

• X-ray of appendicular skeleton area of interest is rated 9/9 (usually appropriate) for suspected rheumatoid arthritis 1
• X-ray of appendicular skeleton area of interest is rated 9/9 for suspected seronegative spondyloarthropathy 1
• For axial symptoms, obtain X-ray of sacroiliac joints and spine initially 1

Advanced Imaging When Radiographs Are Normal or Equivocal

MRI without contrast (rated 7/9) complements radiography when: 1, 4

• Clinical examination suggests inflammatory arthritis but radiographs are normal 1, 4
• Early synovitis detection is needed 4
• Bone marrow lesions, meniscal tears, or cartilage damage suspected in knee pain with normal radiographs 4

Ultrasound (rated 7/9) complements radiography for: 1

• Detecting synovitis and erosions not visible on plain films 1
• Identifying tophi in gout (sensitivity 65%, specificity 80% for soft tissue tophi) 1
• Evaluating chondrocalcinosis in pseudogout 1

Common pitfall: Approximately 20% of patients undergo MRI without recent radiographs (within past year), which is inappropriate; always obtain plain radiographs first 4

Specific Differential Diagnoses

Rheumatoid Arthritis

• Swelling of MCP 2 or 5, proximal interphalangeal (PIP) 2 or 3, wrist swelling/tenderness 5
• Positive RF and anti-CCP antibodies 2, 5
• Symmetric polyarticular distribution 1

Seronegative Spondyloarthropathy

• Enthesitis (inflammation at tendon/ligament insertions) 1
• Axial involvement (sacroiliitis, inflammatory back pain) 1
• Asymmetric oligoarticular pattern 1

Crystal Arthropathy

Gout: Radiography shows characteristic erosions with overhanging edges; ultrasound demonstrates "double contour sign" (sensitivity 83%, specificity 76%) 1

Pseudogout (CPPD): Radiography shows chondrocalcinosis in triangular fibrocartilage of wrists, menisci of knees, symphysis pubis; characteristic involvement of radiocarpal, metacarpophalangeal, and patellofemoral joints 1

Osteoarthritis

• Bony enlargement without warmth 2
• Distal interphalangeal and first carpometacarpal joint involvement 1
• Pain worsens with activity 3

Erosive Osteoarthritis

• Central erosions involving interphalangeal joints on radiography 1
• Mimics inflammatory arthritis but distinct radiographic pattern 1

Systemic Lupus Erythematosus

• Positive ANA 2
• Non-erosive arthritis 2
• Systemic features (rash, serositis, renal involvement) 2

Referral Criteria

Refer to rheumatology within 6 weeks of symptom onset if: 2, 5

• Arthritis involves more than one joint with swelling not caused by trauma or bony enlargement 2
• Any of the following high-specificity variables present: loss of appetite, swelling of MCP 2 or 5, swelling of PIP 2 or 3, wrist swelling, wrist tenderness, positive RF, positive anti-CCP 5

Earlier treatment initiation improves outcomes in inflammatory arthritis 2

Initial Symptomatic Management

Before rheumatology consultation: 2

• Consider NSAIDs (such as naproxen 500 mg twice daily) after evaluating gastrointestinal, renal, and cardiovascular status 2
• Avoid starting DMARDs (like methotrexate) until rheumatology consultation, as these require specific monitoring protocols and should be initiated by specialists 2, 6

Special Considerations

For knee pain with normal radiographs: 4

• Assess for referred pain from hip (examine for range of motion limitations, groin pain, positive impingement signs) or lumbar spine (radiculopathy, neurogenic claudication) 4
• If hip or lumbar pathology suspected, obtain appropriate radiographs before proceeding to knee MRI 4
• MRI without contrast is indicated when radiographs are normal or show only effusion and pain persists 4

For axial symptoms with suspected spondyloarthropathy: 1

• Initial evaluation with radiography of sacroiliac joints and symptomatic spine areas 1
• MRI of sacroiliac joints if radiographs normal but clinical suspicion high 1
• MRI spine may establish diagnosis when other imaging negative; request should specify evaluation for axial spondyloarthropathy to ensure appropriate sequences (STIR or T2-weighted fat-saturated) 1