Gout vs Pseudogout: How to Tell Them Apart
Gout and pseudogout are both crystal-induced inflammatory arthropathies that produce acute, painful monoarticular attacks and trigger the same NLRP3 inflammasome cascade. The core axis that separates them is the crystal itself: monosodium urate in gout versus calcium pyrophosphate dihydrate (CPPD) in pseudogout, which drives differences in crystal morphology, birefringence, joint distribution, and radiographic findings.
How to tell them apart
| Feature | Gout | Pseudogout (CPPD Disease) |
|---|---|---|
| Crystal composition | Monosodium urate (MSU) | Calcium pyrophosphate dihydrate (CPPD) |
| Crystal shape | Needle-shaped | Rhomboid-shaped |
| Birefringence | Negatively birefringent (yellow when parallel to polarizing light) | Weakly positively birefringent (blue when parallel) |
| Classic joint distribution | First MTP most common (podagra); knee second most common; can affect any joint | Typically affects the knee and wrist |
| Radiographic findings | May be normal early; "punched out" erosions with overhanging edges, soft tissue tophi, preserved joint space until late | Chondrocalcinosis—linear calcification of cartilage in menisci and triangular fibrocartilage of the wrist |
| Intensity of inflammation | Exquisitely painful; patient cannot tolerate even a bedsheet on the joint | Similar inflammatory cascade but typically less severe |
| Key risk factors | Male sex, postmenopausal women, purine-rich diet (red meat, shellfish, beer, fructose), thiazide/loop diuretics, chronic kidney disease, obesity, metabolic syndrome | Advanced age, hemochromatosis, hyperparathyroidism, hypomagnesemia |
| Disease-modifying therapy | Urate-lowering therapy available (xanthine oxidase inhibitors, uricosurics, recombinant uricase) targeting serum uric acid below saturation | No equivalent to urate-lowering therapy; no way to dissolve CPPD crystals |
The reasoning
For any acute monoarthritis, aspirate the joint—synovial fluid analysis is the anchor. Under polarized light, crystal shape and birefringence decide the diagnosis: needle-shaped and negatively birefringent means gout; rhomboid and positively birefringent means pseudogout. Distribution and radiographs corroborate: podagra with punched-out erosions points to gout, while a knee or wrist attack with chondrocalcinosis points to CPPD. Risk-factor context helps—a diuretic-using patient with a purine-rich diet and elevated uric acid favors gout, whereas an elderly patient or one with hemochromatosis, hyperparathyroidism, or hypomagnesemia favors CPPD.
Key tests
- Synovial fluid polarized microscopy (gold standard): gout shows needle-shaped, negatively birefringent MSU crystals; pseudogout shows rhomboid, weakly positively birefringent CPPD crystals
- Plain radiographs: gout shows punched-out erosions with overhanging edges and soft tissue tophi; pseudogout shows chondrocalcinosis (linear cartilage calcification in menisci and wrist)
- Serum uric acid: often elevated in gout (though may be normal during an acute attack) and not a feature of pseudogout—but it is supportive, not diagnostic
What they share
- Both are crystal arthropathies—inflammatory but not autoimmune
- Crystals activate the NLRP3 inflammasome with IL-1β release and neutrophil influx
- Both present as acute monoarthritis with a hot, swollen, painful joint
- Both are diagnosed by synovial fluid analysis under polarized microscopy
- Acute attacks are treated similarly with NSAIDs, colchicine, and glucocorticoids
- Septic arthritis can coexist with either—finding crystals does not rule out infection
Pitfalls
- Assuming a hot, swollen joint in a known gout patient is just a flare—septic arthritis can coexist, and crystals do not exclude infection; aspirate and cover for both when there is any concern
- Relying on serum uric acid to diagnose or exclude gout—it can be normal during an acute attack as urate shifts into the joint, and many with hyperuricemia never develop gout
- Starting urate-lowering therapy during an acute gout attack, which can worsen or prolong the flare—wait until after resolution and add colchicine prophylaxis
- Expecting to "dissolve" or reverse pseudogout with a CPPD-lowering drug—no such therapy exists; management is anti-inflammatory only
- Confusing the birefringence: gout is needle-shaped and negative, pseudogout is rhomboid and positive—mixing these up is a classic exam trap
Practice this the way the exam tests it — on branching cases where your decisions shape the patient.