Pseudogout (CPPD disease)
- Lesion
Calcium pyrophosphate crystals deposit in cartilage, mostly in older people, and can set off gout-like attacks, often in the knee or wrist.
What it is
Calcium pyrophosphate dihydrate (CPPD) deposition disease is crystal deposition in articular cartilage, menisci and other joint tissues. It is usually sporadic and age-related, sometimes hereditary (ANKH mutations), and sometimes secondary to metabolic diseases such as hyperparathyroidism, haemochromatosis, hypomagnesaemia, hypophosphatasia and hypothyroidism. It may be silent (chondrocalcinosis on X-ray), cause acute attacks (pseudogout), or produce a chronic arthritis that resembles osteoarthritis.
Structure
- Gross: chalky white, friable deposits in cartilage.
- Micro: oval purple-blue aggregates of crystals in cartilage, menisci and synovium on H&E (better seen than urate because they survive processing).
- Acute attack: neutrophilic synovitis with phagocytosed crystals.
- Chronic: cartilage degeneration like osteoarthritis but in unusual joints (wrist, MCP, shoulder).
Step by step
- Chondrocytes make excess inorganic pyrophosphate (aging, ANKH variants, metabolic disease).
- Pyrophosphate combines with calcium in the matrix and crystallizes.
- Crystals accumulate silently in cartilage (chondrocalcinosis).
- Released into the joint, they activate the inflammasome and draw neutrophils: acute pseudogout.
- Chronic deposits accelerate cartilage degeneration.
Gout vs pseudogout
| Feature | Gout | Pseudogout (CPPD) |
|---|---|---|
| Crystal | Monosodium urate | Calcium pyrophosphate dihydrate |
| Shape and birefringence | Needles, negative | Rhomboids, weakly positive |
| Typical joint | First MTP (big toe) | Knee, wrist |
| Age and sex | Middle-aged men, postmenopausal women | Older adults, both sexes |
| X-ray | Punched-out erosions with overhanging edges | Chondrocalcinosis |
| Associations | Hyperuricaemia, CKD, diuretics, alcohol | Hyperparathyroidism, haemochromatosis, low magnesium |
Clinical notes
- An older patient with a hot knee after surgery: aspirate to look for CPPD crystals and to exclude infection.
- Treatment controls inflammation (joint aspiration, NSAIDs, colchicine, glucocorticoids); there is no drug that removes the crystals.
- Screening for calcium, magnesium, phosphate, iron studies and thyroid function finds secondary causes.
Test yourself
Think of the answer, then tap the question to see it.
How do CPPD crystals look under polarized light?
Rhomboid and weakly positively birefringent.
What is chondrocalcinosis?
Calcification of articular cartilage and menisci seen on X-ray in CPPD disease.
Which metabolic diseases are linked to CPPD?
Hyperparathyroidism, haemochromatosis, hypomagnesaemia, hypophosphatasia and hypothyroidism.
Which joint is most often affected by pseudogout?
The knee.
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Calcium pyrophosphate arthritis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Gout (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.