On the venous origin of primary gout: The barotoxicity hypothesis

Gout is the oldest and the most prevalent inflammatory joint disease worldwide exhibiting a steady increase in both incidence and prevalence. Despite millennia of rigorous clinical research, specific pivotal questions still need to be fully elucidated. Presently, the exact initial defect that induces its most prevalent type—primary hyperuricemia and primary gout—remains idiopathic. Additionally, the remarkable predilection for foot involvement (podagra), its exceptionally intense pain, and the precise mechanism triggering acute gout attack all lack clear pathological processes. This manuscript aims to demystify the aforementioned dilemmas by presenting the barotoxicity hypothesis which introduces the barotoxic effect of intra-abdominal pressure on the renal and pedal venous circulations as the potential origin of primary hyperuricemia and the subsequent podagra formation in addition to presenting evidence in support of this hypothesis. If validated, the barotoxicity hypothesis could radically transform our modern understanding of this ancient ailment, reframing gout from being a metabolic arthropathy to a mechanical phlebopathy. Moreover, future therapeutic interventions could pivot towards alleviating intra-abdominal pressure and subsequent peripheral venous stasis, offering innovative preventative and therapeutic approaches.