From the Guidelines
Gout is caused by the accumulation of uric acid crystals in joints, leading to painful inflammation, which occurs when the body either produces too much uric acid or cannot efficiently eliminate it through the kidneys, as supported by the 2017 study 1. The mechanism of gout involves the deposition of monosodium urate monohydrate crystals in supersaturated extracellular fluids of the joint, and certain other sites, mediating most of the clinical and pathologic features of gout, as described in the 2012 guidelines 1. Some key points about the mechanism of gout include:
- Uric acid is a normal breakdown product of purines, which are found in certain foods and also produced naturally by the body.
- When uric acid levels in the blood become too high (hyperuricemia), needle-like monosodium urate crystals form and deposit in joints, particularly the big toe, ankles, knees, and elbows.
- These crystals trigger an intense inflammatory response as the immune system attempts to remove them, causing the classic symptoms of a gout attack: severe pain, redness, swelling, and warmth in the affected joint.
- Certain factors increase the risk of gout, including diet high in purines (red meat, seafood, alcohol), obesity, certain medications, and genetic factors affecting uric acid metabolism, as noted in the 2017 systematic review 1. The most recent and highest quality study, the 2017 systematic review 1, provides moderate-strength evidence that low-dose colchicine is as effective as high-dose colchicine and causes fewer gastrointestinal adverse events, and high-strength evidence shows that prophylaxis with daily colchicine or NSAIDs reduces the risk for acute gout attacks by at least half in patients starting urate-lowering therapy. Some important considerations for the management of gout include:
- Treatment typically involves medications like colchicine, NSAIDs, or corticosteroids for acute attacks.
- Long-term management focuses on lowering uric acid levels with drugs such as allopurinol or febuxostat.
- Lifestyle modifications including weight loss, limiting purine-rich foods, reducing alcohol intake, and staying well-hydrated are also essential for preventing recurrent gout attacks, as supported by the 2012 guidelines 1 and the 2017 systematic review 1.
From the FDA Drug Label
Gout is a metabolic disorder which is characterized by hyperuricemia and resultant deposition of monosodium urate in the tissues, particularly the joints and kidneys. The etiology of this hyperuricemia is the overproduction of uric acid in relation to the patient's ability to excrete it The mechanism of gout is a metabolic disorder characterized by hyperuricemia, which is the overproduction of uric acid in relation to the patient's ability to excrete it, leading to the deposition of monosodium urate in tissues, particularly the joints and kidneys 2.
From the Research
Mechanism of Gout
The mechanism of gout involves the deposition of monosodium urate crystals within the synovium of joints, leading to severe pain and reducing quality of life for patients with this condition 3. This deposition is caused by hyperuricemia, which results from increased production of uric acid and decreased excretion by the kidneys and intestines 4.
Hyperuricemia
Hyperuricemia is the primary mechanism of gout, and it is regulated by a group of urate transporters 4. Genetic variability in these urate transporters is strongly related to variances in serum urate levels 4. Decreased renal or intestinal excretion is the primary mechanism of hyperuricemia in most people 4.
Inflammatory Response
The initiation of the inflammatory response to monosodium urate crystals is mainly mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing protein 3 (NLRP3) inflammasome 4. The activated NLRP3 inflammasome complex cleaves pro-interleukin-1β (IL-1β) into its active form, IL-1β, which is a key mediator of the inflammatory response in gout 4. IL-1β leads to the upregulation of cytokines and chemokines, resulting in the recruitment of neutrophils and other immune cells 4.
Key Factors
Some key factors in the mechanism of gout include:
- Deposition of monosodium urate crystals in the joints and soft tissues 3, 5, 6, 4, 7
- Hyperuricemia, resulting from increased production of uric acid and decreased excretion by the kidneys and intestines 4
- Activation of the NLRP3 inflammasome and subsequent release of IL-1β 4
- Recruitment of neutrophils and other immune cells to the site of inflammation 4
Chronic Gout
Chronic gout is characterized by the deposition of solid monosodium urate crystal aggregates in a variety of tissues, including joints, bursae, and tendons 7. Tophi can occur in a variety of locations, including the helix of the ear, olecranon bursa, and over the interphalangeal joints 7. Their development is usually related to both the degree and the duration of hyperuricemia 7.