Crystal-induced inflammation in gout and CPPD: the NLRP3 inflammasome
Why urate crystallises (solubility, temperature, renal handling with a worked fractional excretion), how crystals trigger the NLRP3 inflammasome and IL-1 beta, why flares stop on their own, and how colchicine, IL-1 blockers and urate-lowering drugs act.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Gout and calcium pyrophosphate (CPP) disease are innate immune diseases. Crystals, not antigens, trigger inflammation, and there is no autoantibody or T-cell memory.
- Crystals are phagocytosed by macrophages and activate the NLRP3 inflammasome, which releases IL-1 beta. IL-1 then recruits a flood of neutrophils.
- The physical chemistry of urate explains the distribution of gout, and renal handling explains most hyperuricaemia.
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Sources
- Therapeutic Guidelines: Rheumatology (gout; calcium pyrophosphate deposition)AU/NZTherapeutic Guidelines Limited (eTG complete), current online version, accessed November 2026
- Firestein and Kelley's Textbook of Rheumatology (11th ed.)Elsevier, 2021
- Martinon F et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006;440:237-41Nature, 2006
- Schauer C et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med 2014;20:511-7Nature Medicine, 2014
- Dalbeth N, Gosling AL, Gaffo A, Abhishek A. Gout. Lancet 2021;397:1843-55The Lancet, 2021
- FitzGerald JD et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res 2020;72:744-60American College of Rheumatology, 2020
- Terkeltaub RA et al. High versus low dosing of oral colchicine for early acute gout flare (AGREE). Arthritis Rheum 2010;62:1060-8Arthritis and Rheumatism, 2010
- Ichida K et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun 2012;3:764Nature Communications, 2012
- Ilaris (canakinumab) Australian Product InformationAU/NZNovartis Pharmaceuticals Australia / TGA, accessed November 2026
- Last updated
- 14 November 2026
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