Gout in the era of multimorbidity: pathogenesis, systemic comorbidities, and evolving therapeutic strategies

Gout is the most prevalent inflammatory arthritis worldwide and represents a growing global health burden. It arises from hyperuricemia resulting from disordered purine metabolism, leading to monosodium urate (MSU) crystal deposition and recurrent inflammatory arthritis. Although hyperuricemia is the principal risk factor, genetic susceptibility, impaired urate transport, and emerging factors such as the gut microbiota also contribute to disease development. Acute flares are mediated by MSU crystal-induced activation of the NLRP3 inflammasome and subsequent interleukin-1β production, whereas chronic inflammation results in tophus formation and structural joint damage. Gout is closely associated with metabolic syndrome, chronic kidney disease, and cardiovascular disease, which contribute to persistently elevated mortality. Although advances in imaging and pharmacologic therapy have improved diagnosis and management, the real-world use of urate-lowering therapy remains suboptimal. Further research and sustained efforts by healthcare professionals are needed to improve long-term disease control.