What is the differential diagnosis for sudden onset foot pain and warmth at the metatarsophalangeal (MTP) joint with elevated C-reactive protein (CRP), slight increase in alkaline phosphatase (alk phos), and bony erosion on X-ray, following gardening?

Differential Diagnosis: Acute Monoarticular MTP Joint Inflammation with Bony Erosion

The most likely diagnosis is acute gout, given the sudden onset after physical activity (gardening), warm and painful MTP joint, elevated CRP with normal ESR, and bony erosion on X-ray—a presentation highly consistent with crystal arthropathy. 1

Primary Differential Considerations

1. Gout (Most Likely)

• Monoarthritis of the first MTP joint has 99% sensitivity for gout when presenting acutely 1
• The sudden onset after gardening (physical trigger), warmth, and pain at the MTP joint are classic features 1
• Elevated CRP with normal ESR is consistent with acute crystal inflammation 1
• Bony erosion on X-ray supports chronic tophaceous gout with acute flare 1
• Normal WBC does not exclude gout—systemic leukocytosis is not required for diagnosis 1
• The Clinical Gout Diagnosis (CGD) criteria show 97% sensitivity and 96% specificity when 4 or more of 8 criteria are met 1

Critical next step: Joint aspiration for monosodium urate (MSU) crystal analysis remains the gold standard, showing needle-shaped negatively birefringent crystals 1

2. Septic Arthritis (Must Exclude Urgently)

• The warm, painful joint with sudden onset requires immediate consideration of infection 1
• However, several features argue against septic arthritis:
  • Normal WBC count (bacteremia typically causes leukocytosis) 2
  • Normal ESR (usually elevated in bacterial infection) 1
  • Elevated GGT and alkaline phosphatase suggest metabolic rather than infectious process 2
  • Absence of systemic symptoms (fever, chills) makes infection less likely 1

Critical action: If any clinical suspicion remains, perform urgent arthrocentesis with synovial fluid analysis including cell count (>50,000 WBC/mm³ suggests septic arthritis), Gram stain, and culture 3

3. Psoriatic Arthritis

• Can present with MTP joint involvement and bony erosion 4
• "Sausage toe" appearance (dactylitis) is characteristic 1
• Key distinguishing features to assess:
  • History of psoriasis or nail dystrophy 1
  • Asymmetric inflammatory arthritis pattern 1
  • Juxta-articular new bone formation on radiography 1
• Elevated CRP with normal ESR can occur in seronegative spondyloarthropathies 4

4. Adult-Onset Still's Disease (Less Likely)

• MTP involvement occurs in only 11-18% of AOSD cases 1
• Features that do NOT fit AOSD:
  • Absence of fever (100% of AOSD patients have fever) 1
  • Normal WBC (AOSD typically shows marked leukocytosis >15,000-20,000/mm³) 1
  • Normal ESR (virtually always elevated in AOSD) 1
  • Absence of characteristic salmon-pink rash 1

5. Chronic Non-Bacterial Osteitis (CNO)

• Bony erosion with elevated CRP but normal ESR could suggest CNO 1
• However, CNO more commonly affects anterior chest wall, spine, and mandible rather than isolated MTP joint 1
• Typically presents with insidious rather than sudden onset 1

Laboratory Pattern Analysis

The specific laboratory constellation is highly informative:

• Elevated GGT with normal AST: Suggests metabolic process rather than hepatocellular injury; can be elevated in gout due to alcohol use or metabolic syndrome 1
• Elevated CRP with normal ESR (dissociation): This pattern is characteristic of acute crystal arthropathy rather than chronic inflammatory conditions 1, 3
• Normal WBC: Excludes most bacterial infections and AOSD 1, 2
• Slightly elevated platelets: Reactive thrombocytosis from acute inflammation 1
• Slightly elevated alkaline phosphatase: Can occur with bone turnover from erosive process 2, 5

Recommended Diagnostic Algorithm

Immediate (within 24 hours):

1. Arthrocentesis of affected MTP joint for synovial fluid analysis 3:

   • Cell count with differential (>2,000 WBC/mm³ suggests inflammatory; >50,000 suggests septic) 3
   • Polarized microscopy for MSU crystals (needle-shaped, negatively birefringent) 1
   • Gram stain and culture to exclude infection 3

2. Serum uric acid level (though normal level does not exclude acute gout) 1

If crystal analysis confirms gout:

• Initiate anti-inflammatory therapy (NSAIDs, colchicine, or corticosteroids) 1
• Address underlying hyperuricemia after acute attack resolves 1

If crystals negative but high clinical suspicion:

• Consider repeat aspiration (sensitivity increases with multiple attempts) 1
• MRI or ultrasound may show "double contour sign" characteristic of urate deposition 3

Critical Pitfalls to Avoid

• Do not rely on normal WBC or ESR to exclude infection—low-grade infections, particularly with coagulase-negative staphylococci, can present with normal inflammatory markers 6, 7
• Do not assume normal CRP excludes infection—23-32% of culture-positive prosthetic joint infections have normal CRP, particularly chronic low-grade infections 6, 7
• Do not delay arthrocentesis—joint aspiration is essential and should be performed before initiating antibiotics if infection is suspected 1, 3
• Do not dismiss gout based on normal serum uric acid—up to 40% of acute gout attacks occur with normal uric acid levels 1