Distinguishing Gout from Pseudogout

Crystal Composition and Pathophysiology

Gout is caused by monosodium urate crystal deposition, while pseudogout results from calcium pyrophosphate dihydrate crystal deposition, requiring synovial fluid analysis for definitive differentiation, as recommended by the American College of Physicians 1, 2
Monosodium urate monohydrate crystals form when serum urate exceeds 6.8-7.0 mg/dL, depositing in joints, cartilage, tendons, and soft tissues, according to the American College of Rheumatology 3
Calcium pyrophosphate dihydrate crystals deposit in cartilage, tendons, ligaments, and joint capsules, as noted by the American College of Radiology 4

Gout characteristically affects the first metatarsophalangeal joint, and may present as acute monoarticular or chronic polyarticular disease, with risk factors including male sex, obesity, hypertension, excess alcohol intake, and diuretic use, as reported by the American College of Physicians 2, 3
Pseudogout characteristically affects larger joints, such as the knees, and often mimics osteoarthritis in atypical distributions, with associations including older age, multiple medical comorbidities, and metabolic and endocrine disorders, as described by the American College of Radiology 4, 5, 6

The American College of Physicians recommends synovial fluid analysis when clinical judgment indicates diagnostic testing is necessary for suspected acute gout, with crystal identification under compensated polarized light microscopy being diagnostic 1, 2
Radiography should be the initial imaging method for both conditions, with gout imaging findings including erosions with overhanging edges, and soft tissue tophi, as noted by the American College of Radiology 6, 7
Pseudogout imaging findings include chondrocalcinosis, calcification of tendons, ligaments, and joint capsules, and arthropathy involving radiocarpal, metacarpophalangeal, and patellofemoral joints, as described by the American College of Radiology 4, 5, 6, 7

Both conditions respond to similar anti-inflammatory approaches, including NSAIDs, colchicine, or corticosteroids for acute attacks, as recommended by the American College of Physicians 8
Gout has disease-modifying therapy, including urate-lowering therapy, which reduces long-term attack risk, and prophylaxis with daily colchicine or NSAIDs during ULT initiation, as reported by the American College of Physicians 8
Pseudogout lacks crystal-reducing therapy, with treatment focusing on symptom relief only, and colchicine may serve as prophylaxis for recurrent attacks, as noted by the American College of Physicians 8

Monoarticular or oligoarticular involvement is a characteristic feature of acute CPPD crystal arthritis, distinguishing it from polyarticular presentations, according to the Annals of the Rheumatic Diseases 9
Crowned dens syndrome presents as acute neck pain with calcification around the odontoid process, as reported by the Annals of the Rheumatic Diseases 10

Pseudogout can coexist with septic arthritis, necessitating synovial fluid analysis for both crystal identification and Gram stain/culture, as noted by the Annals of the Rheumatic Diseases 10

Recurrent acute attacks affecting different large joints are a key diagnostic indicator of pseudogout, as reported by the Annals of the Rheumatic Diseases 9