How to differentiate and treat a patient with a swollen 3rd toe, suspected of having either arthritis or gout, with a potential history of joint pain or inflammation?

Differentiating and Treating a Swollen 3rd Toe: Arthritis vs Gout

For a swollen 3rd toe, joint aspiration with synovial fluid analysis for monosodium urate (MSU) crystals under polarized light microscopy is the definitive diagnostic test and should be attempted whenever feasible, as this provides near 100% sensitivity and specificity for gout diagnosis. 1, 2

Immediate Diagnostic Approach

Step 1: Attempt Joint Aspiration (Gold Standard)

• Perform arthrocentesis to obtain synovial fluid for crystal analysis, which remains the reference standard for diagnosing gout with sensitivity 63-78% and specificity 93-100% when performed by experienced operators 2, 3
• MSU crystals appear as needle-shaped, negatively birefringent crystals under polarized light microscopy 2, 3
• Always perform Gram stain and culture even when MSU crystals are identified, as gout and septic arthritis can coexist 2, 3
• Joint aspiration is mandatory when septic arthritis cannot be clinically excluded, or when this is the patient's first suspected gout attack 3

Step 2: Clinical Assessment (When Aspiration Not Feasible)

Key clinical features that strongly suggest gout over other arthritis:

• Rapid onset of severe pain reaching maximum intensity within 6-24 hours (odds ratio 3.58 for gout) 2, 3
• Overlying erythema with severe tenderness over the affected joint 1, 2
• History of previous similar acute episodes with complete resolution between attacks 1, 3
• Male gender and associated cardiovascular diseases 1

Critical risk factors to document:

• Chronic kidney disease (relative risk 4.95) 2
• Obesity (relative risk 3.81) 2
• Hypertension (relative risk 3.93) 2
• Diuretic use (relative risk 1.72) 2
• Alcohol consumption, particularly beer and spirits 1
• Diet high in meat, shellfish, and high-fructose corn syrup 1, 2

Step 3: Laboratory Testing

• Measure serum uric acid level, but never diagnose gout based on hyperuricemia alone, as only 22% of patients with uric acid >9 mg/dL develop gout within 5 years 3
• However, normal serum uric acid essentially rules out gout in the clinical context 2, 3
• Hyperuricemia alone has only 53-61% specificity for gout 2
• Measure ESR and CRP at baseline for diagnosis and prognosis of inflammatory arthritis 1

Step 4: Imaging (When Aspiration Not Possible)

First-line imaging: Ultrasound

• Ultrasound should be the initial advanced imaging modality when joint aspiration is not feasible 2, 3
• Look for the "double contour sign" at cartilage surfaces (sensitivity 74%, specificity 88%) 1, 2
• Detect tophi appearing as hyperechoic masses with "wet clumps of sugar" appearance (sensitivity 65%, specificity 80%) 2
• Always scan the first metatarsophalangeal joint bilaterally, even if asymptomatic, as this is the disease-specific target site 2, 3
• Ultrasound performs better in late disease (>2 years duration) with 63% sensitivity compared to 50% in early disease 2

Second-line imaging: Dual-Energy CT (DECT)

• Use DECT when ultrasound is inconclusive and disease duration >2 years (sensitivity 85-100%, specificity 83-92%) 1, 2, 3
• DECT is less sensitive in early disease (<2 years) 2, 3
• When characteristic features of MSU crystal deposition are identified on ultrasound or DECT, synovial fluid analysis is not needed to confirm diagnosis 1, 2

Plain radiographs:

• Have limited value for diagnosing acute gout flares 1
• Useful only for assessing chronic structural damage in long-standing gout 1, 2

Treatment Algorithm

Acute Gout Attack Treatment

Immediate anti-inflammatory therapy (choose based on contraindications):

• NSAIDs are the preferred first-line treatment for acute gout 4
• The most critical factor for success is how soon treatment is initiated, not which specific agent is chosen 4
• Alternative options include oral colchicine, intra-articular or systemic corticosteroids, or intramuscular corticotropin 4
• Prednisone is indicated for acute gouty arthritis when NSAIDs are contraindicated 5
• Nonpharmacological treatments such as topical ice and rest of the inflamed joint are useful adjuncts 4

Prophylaxis During Urate-Lowering Therapy Initiation

• Maintenance doses of colchicine should be given prophylactically when starting allopurinol to prevent acute flares 6
• Continue colchicine or anti-inflammatory agents until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months 6
• Acute attacks usually become shorter and less severe after several months of urate-lowering therapy 6

Long-Term Urate-Lowering Therapy

Indications for urate-lowering therapy:

• Recurrent gout attacks (more than one previous episode) 3, 4
• Presence of tophi 4, 7
• Chronic gouty arthritis 4

Allopurinol dosing protocol:

• Start with 100 mg daily and increase at weekly intervals by 100 mg until serum uric acid level of 6 mg/dL or less is attained (maximum 800 mg daily) 6
• Target serum uric acid: ≤6 mg/dL (or potentially lower to 0.36 mmol/L in those with tophi) 6, 7
• Normal serum urate levels are usually achieved in 1-3 weeks 6
• Allopurinol is better tolerated if taken following meals 6

Renal dosing adjustments:

• Creatinine clearance 10-20 mL/min: 200 mg daily 6
• Creatinine clearance <10 mL/min: maximum 100 mg daily 6
• Extreme renal impairment (creatinine clearance <3 mL/min): may need to lengthen interval between doses 6

Fluid management:

• Maintain fluid intake sufficient to yield daily urinary output of at least 2 liters 6
• Maintain neutral or slightly alkaline urine to prevent xanthine calculi formation 6

Critical Pitfalls to Avoid

• Never diagnose gout based on hyperuricemia alone (only 53-61% specificity) 1, 3
• Do not skip joint aspiration when septic arthritis cannot be clinically excluded, as the relatively low specificity of clinical algorithms raises risk for missed septic arthritis 2, 3
• Do not rely on imaging alone—integrate patient history, physical examination, and laboratory findings 2, 3
• Do not use plain radiographs as the primary diagnostic modality for acute gout 1, 2
• Ultrasound sensitivity is significantly lower in early disease (<2 years), with only 50% for double contour sign versus 63% in late disease 2
• Patients with decreased renal function require lower doses of allopurinol than those with normal renal function 6
• An increase in acute gout attacks may occur during early stages of allopurinol administration, even when normal serum uric acid levels are attained, necessitating prophylactic colchicine 6