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The natural history of gout typically consists of three periods in a continuum: asymptomatic hyperuricaemia, episodes of acute attacks of gout with asymptomatic intervals, and chronic gouty arthritis.1 The last decade has seen major advances in our knowledge of acute attacks of gout with the discovery of the pivotal role of interleukin 1 (IL-1);2 however, the mechanisms that trigger acute flares are still poorly known. For instance, despite the incidence of gout increasing exponentially with increasing urate levels,3 why gout develops in only a few patients with asymptomatic hyperuricaemia is unclear. In addition, we do not know why acute attacks of gout are so sporadic in patients with established tophaceous gout, despite their massive total body urate load.
In this context, the elegant report from Zhang et al4 published in this issue adds a piece of the puzzle to help unravel the mystery of acute attacks of gout. Indeed, this report shows for the first time, that high purine intake, in addition to being a well-known long-term risk factor of urate deposition, also increases the risk of gout attacks almost fivefold among patients with gout. The natural question resulting from this work is: How does acute purine intake trigger acute attacks of gout?
Monosodium urate (MSU) crystals within the joint: necessary but not sufficient for acute flares
Uric acid is the final metabolite of endogenous and dietary purine metabolism. At a physiologic pH of 7.4 in the extracellular compartment, 98% of uric acid is in the ionised form of urate. Because of the high concentration of sodium in the extracellular compartment, urate is largely present as MSU, with a low solubility limit, approximately 380 µmol/l at 37°C. When urate concentration exceeds the saturation point, the risk of MSU crystal formation and precipitation increases.1
Ultrasound studies have …
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