Three contradictory clinical presentations of gout have puzzled clinicians and basic scientists for some time: first, the crescendo of sterile inflammation in acute gouty arthritis; second, its spontaneous resolution, despite monosodium urate (MSU) crystal persistence in the synovium; and third, immune anergy to MSU crystal masses observed in tophaceous or visceral gout. Here, we provide an update on the molecular pathophysiology of these gout manifestations, namely, how MSU crystals can trigger the auto-amplification loop of necroinflammation underlying the crescendo of acute gouty arthritis. We also discuss new findings, such as how aggregating neutrophil extracellular traps (NETs) might drive the resolution of arthritis and how these structures, together with granuloma formation, might support immune anergy, but yet promote tissue damage and remodeling during tophaceous gout.

痛风的三个相互矛盾的临床表现使临床医生和基础科学家困惑了一段时间：首先，急性痛风性关节炎无菌性炎症的加重。第二，尽管尿酸单钠（MSU）晶体持续存在于滑膜中，但它具有自发的分辨率。第三，在口腔或内脏痛风中观察到对MSU晶体块的免疫无反应。在这里，我们提供了有关这些痛风表现的分子病理生理学的最新信息，即MSU晶体如何触发急性痛风性关节炎加重下的坏死性炎症的自动扩增环。我们还将讨论新的发现，例如，嗜中性粒细胞胞外诱集剂（NETs）的聚集如何驱动关节炎的消退，以及这些结构以及肉芽肿的形成如何可能支持免疫无能，