What is the difference between gout and pseudogout?

Distinguishing Gout from Pseudogout

Gout is caused by monosodium urate (MSU) crystal deposition, while pseudogout results from calcium pyrophosphate dihydrate (CPPD) crystal deposition—these are fundamentally different crystalline arthropathies that require synovial fluid analysis for definitive differentiation. 1

Crystal Composition and Pathophysiology

The fundamental distinction lies in the crystal type:

• Gout: Monosodium urate monohydrate crystals form when serum urate exceeds 6.8-7.0 mg/dL, depositing in joints, cartilage, tendons, and soft tissues 1, 2
• Pseudogout: Calcium pyrophosphate dihydrate crystals deposit in cartilage, tendons, ligaments, and joint capsules 1, 3

Both conditions trigger acute inflammatory responses through NLRP3 inflammasome activation and IL-1β release, explaining their similar clinical presentations 4

Clinical Presentation Differences

Joint Distribution Patterns

Gout characteristically affects:

• First metatarsophalangeal joint (big toe) most commonly 2, 5
• Can involve fingers, especially in elderly patients on diuretics 2
• May present as acute monoarticular or chronic polyarticular disease 1, 2

Pseudogout characteristically affects:

• Larger joints (knees most commonly) 6
• Radiocarpal, metacarpophalangeal, atlantoaxial, and patellofemoral joints 1
• Often mimics osteoarthritis in atypical distributions 2, 3

Demographic and Risk Factor Differences

Gout risk factors include:

• Male sex, obesity, hypertension 1
• Excess alcohol intake, diet rich in meat and seafood 1
• Diuretic use, poor kidney function 1
• In elderly: commonly affects women, associated with diuretic usage 2

Pseudogout associations:

• Older age, multiple medical comorbidities 3
• May follow trauma, surgery, or ischemic heart disease 6
• Associated with metabolic and endocrine disorders 3

Diagnostic Approach

Gold Standard: Synovial Fluid Analysis

The American College of Physicians recommends synovial fluid analysis when clinical judgment indicates diagnostic testing is necessary for suspected acute gout. 1 This same principle applies to pseudogout differentiation.

Crystal identification under compensated polarized light microscopy:

• MSU crystals (gout): Needle-shaped, negatively birefringent 6
• CPPD crystals (pseudogout): Rhomboid-shaped, positively birefringent or weakly positive 6
• Presence of crystals within phagocytes from synovial fluid is diagnostic 6

Imaging Characteristics

Radiography should be the initial imaging method for both conditions 1

Gout imaging findings:

• Erosions with overhanging edges 1
• Soft tissue tophi (masses of uric acid crystals) 2
• Joint space typically preserved until late disease 1

Pseudogout imaging findings:

• Hallmark: Chondrocalcinosis (cartilage calcification) 1
• Calcification of tendons, ligaments, and joint capsules 1
• Target sites: triangular fibrocartilage of wrists, knee menisci, symphysis pubis, hip labrum 1
• Arthropathy involving radiocarpal, metacarpophalangeal, and patellofemoral joints 1

Advanced Imaging

Ultrasound findings:

• Gout: Double contour sign (83% sensitivity, 76% specificity), soft tissue tophi (65% sensitivity, 80% specificity) 1
• Pseudogout: Gradient-recalled echo MRI and US outperform radiography for chondrocalcinosis detection 1

Dual-energy CT:

• Shows monosodium urate deposition in gout with 87% sensitivity and 84% specificity 1
• Less accurate for shoulder and hip evaluation 1

Treatment Implications

Acute Management

Both conditions respond to similar anti-inflammatory approaches:

• NSAIDs, colchicine, or corticosteroids for acute attacks 1, 5
• Low-dose colchicine is as effective as high-dose with fewer gastrointestinal adverse events 1

Long-term Management Differences

Gout has disease-modifying therapy:

• Urate-lowering therapy (allopurinol, febuxostat) reduces long-term attack risk after 1+ years 1
• Prophylaxis with daily colchicine or NSAIDs during ULT initiation reduces attack risk by >50% 1
• Dietary modifications, weight reduction, alcohol avoidance are effective 2, 5

Pseudogout lacks crystal-reducing therapy:

• No agents available to decrease CPPD crystal load 3
• Treatment focuses on symptom relief only 3, 5
• Colchicine may serve as prophylaxis for recurrent attacks via NLRP3 inflammasome effects 3
• IL-1 pathway inhibitors considered for severe, refractory cases 3

Critical Clinical Pitfalls

Common diagnostic errors to avoid:

• Assuming clinical presentation alone is sufficient—both can mimic osteoarthritis, rheumatoid arthritis, or septic arthritis 1, 2
• Failing to perform synovial fluid analysis when diagnosis is uncertain 1
• Missing pseudogout in patients with "atypical osteoarthritis" distribution 2
• Overlooking gout in elderly women on diuretics with finger involvement 2
• Confusing the two conditions based on joint size alone—both can affect multiple joint sizes 2, 5

The definitive distinction requires microscopic crystal identification, as clinical features and imaging findings overlap substantially. 6