What is the appropriate initial evaluation and management for a 40-year-old woman with sudden severe joint pain that began this morning?

Sudden Severe Joint Pain in a 40-Year-Old Woman: Initial Evaluation and Management

For sudden onset severe joint pain in a 40-year-old woman, immediately determine if this is monoarticular versus polyarticular involvement, obtain plain radiographs of affected joints, and perform urgent joint aspiration with synovial fluid analysis if septic arthritis or crystal-induced arthritis is suspected. 1, 2

Immediate Clinical Assessment

First, establish the pattern of joint involvement:

• Monoarticular (single joint): Suspect crystal arthropathy (gout, pseudogout) or septic arthritis—these require urgent joint aspiration 2
• Polyarticular (multiple joints): Consider inflammatory arthritis, viral arthritis, or systemic autoimmune disease 1, 2

Key clinical features to assess immediately:

• Timing: Pain reaching maximum severity within 6-12 hours with overlying erythema strongly suggests crystal inflammation, though not specific for gout 3
• Morning stiffness >30 minutes: Indicates inflammatory rather than mechanical causes 1, 2
• Squeeze test: Compress the metacarpophalangeal (MCP) or metatarsophalangeal (MTP) joints—pain with this maneuver strongly indicates inflammatory arthritis 1, 2
• Podagra (first MTP joint involvement): Has a likelihood ratio of 30.64 for gout diagnosis 3

Critical Rule-Out: Septic Arthritis

Joint aspiration with synovial fluid analysis is mandatory if septic arthritis is suspected, as this can rapidly become lethal. 1, 4

Perform synovial fluid analysis for:

• Cell count with differential 1
• Gram stain and culture 1
• Crystal analysis under polarized light microscopy 3, 1

Essential Laboratory Workup

Order the following initial panel immediately: 1

• Complete blood count (CBC): Exclude non-rheumatologic diseases and assess systemic involvement 1, 2
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP): Quantify inflammation and predict persistent/erosive disease 1, 2
• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies: Both predict severe disease and poor prognosis in rheumatoid arthritis 1, 2
• Antinuclear antibodies (ANA): Identify systemic lupus erythematosus and other connective tissue diseases 1, 2
• Urinalysis and transaminases: Exclude non-rheumatologic diseases 1, 2

Additional testing based on clinical presentation:

• Serum uric acid: Note that normal levels during acute attacks do not exclude gout, as levels may be normal during flares 3
• HLA-B27: If symptoms suggest axial involvement or seronegative spondyloarthropathy 1
• Creatine kinase (CK): If true weakness (not just pain) is present to differentiate from myositis 1

Imaging Studies

Plain radiographs of affected joints are the first-line imaging modality with an appropriateness rating of 9/9. 1, 2

Radiographs help:

• Evaluate for structural abnormalities and early signs of arthritis 1, 5
• Detect chondrocalcinosis (calcium pyrophosphate deposition) 2, 6
• Identify erosions with overhanging edges characteristic of gout 2
• Exclude alternative diagnoses like fractures or metastases 1

Important caveat: Radiographs are not useful in confirming early or acute gout, though they help with differential diagnosis 3. Up to 41% of osteochondral abnormalities can be missed on radiography 5.

Advanced imaging if radiographs are normal but symptoms persist:

• MRI without contrast: Detects early inflammatory changes, bone marrow edema, and soft tissue abnormalities not visible on plain films 2, 5
• Ultrasound with power Doppler: Useful for detecting synovitis, erosions, tophi in gout (sensitivity 65%, specificity 80%), and chondrocalcinosis in pseudogout 2

Differential Diagnosis Framework

Crystal-Induced Arthropathy (Most Likely Given Sudden Severe Onset)

Gout:

• Rapid development of severe pain reaching maximum within 6-12 hours 3
• Podagra has the highest likelihood ratio (30.64) for diagnosis 3
• Definite tophus has likelihood ratio of 39.95 3
• Monosodium urate crystals in synovial fluid are definitive (sensitivity 84%, specificity 100%) 3

Pseudogout (Calcium Pyrophosphate Deposition Disease):

• Can mimic gout flares but more common in patients >60 years 6
• Radiographic chondrocalcinosis is characteristic 2, 6
• Positively birefringent CPPD crystals on polarized light microscopy 7

Inflammatory Arthritis

Rheumatoid arthritis:

• Female predominance and symmetrical polyarthritis affecting MCP, PIP, wrists 1
• Positive RF and anti-CCP antibodies predict severe disease 1, 2
• Spares DIP joints 1

Seronegative spondyloarthropathy:

• Asymmetric oligoarticular pattern with enthesitis and axial involvement 2
• Extra-articular features like skin lesions, nail dystrophy, uveitis 1

Initial Symptomatic Management

For acute pain relief while awaiting definitive diagnosis:

• NSAIDs (e.g., naproxen 500 mg twice daily): After evaluating gastrointestinal, renal, and cardiovascular status 1, 2
• Avoid starting DMARDs (like methotrexate) until rheumatology consultation, as these require specific monitoring protocols and should be initiated by specialists 1, 2

For confirmed crystal arthropathy:

• Colchicine, NSAIDs, and/or corticosteroids are first-line agents for acute treatment 8, 6
• Prednisone may provide the best benefit-risk ratio for acute calcium pyrophosphate crystal arthritis 6

Urgent Rheumatology Referral Criteria

Refer to rheumatology within 6 weeks of symptom onset if:

• Arthritis involves more than one joint with swelling not caused by trauma or bony enlargement 1, 2, 5
• Symptoms persist despite initial management 1

Earlier treatment initiation improves outcomes in inflammatory arthritis. 1

Common Pitfalls to Avoid

• Do not rely solely on serum uric acid levels: Many people with hyperuricemia never develop gout, and levels may be normal during acute attacks 3
• False positive RF can occur with: Infections (mononucleosis, cytomegalovirus, parvovirus), other autoimmune diseases (Sjögren's syndrome, systemic lupus, systemic sclerosis), and vasculitis 1
• Always interpret RF in conjunction with anti-CCP and clinical findings 1
• Joint aspiration is mandatory to rule out septic arthritis, which can be rapidly lethal if missed 1, 4
• Radiographs miss early inflammatory changes: Consider MRI or ultrasound if clinical suspicion is high but radiographs are normal 2, 5