Gout is characterized by the deposition of monosodium urate crystals in the extracellular fluid of the joints and other sites, due to disturbances of uric acid metabolism (i.e., either overproduction or underexcretion). This results in joint space destruction, bony erosion and damage to the surrounding ligaments and tendons.
Manifestations are either acute, characterized by severe mono- or polyarticular pain, redness, and swelling of the affected joint; or chronic, characterized by development of monosodium urate crystals in the soft tissues in and around the joints, giving rise to painless swellings referred to as "tophi".
Joint mobility is affected in both forms. In acute disease, this is due to severe pain limiting movement, and in the chronic form, due to longstanding destruction of the joint spaces.
Frequently affected joints include the first metatarsophalangeal joint (i.e. "podagra"), ankle, knee, wrist, finger and elbow. This pattern is due to the fact that urate is more li
kely to crystallize in the cooler areas of the body.
In the early stages of acute gout, X-rays of the affected joint will often be normal, or only show subtle changes such as small erosions. Thus, they are not particularly helpful in establishing the diagnosis.
During an acute attack of gout, serum urate levels may be reduced or normal. The exact mechanism behind this is poorly understood but thought to be due to either increased excretion of uric acid, inflammatory reactions, or increased crystal formation. Therefore, serum urate levels should be rechecked about one to two weeks following resolution of an acute attack.
Arthrocentesis involves the aspiration of synovial fluid from the joint space. The aspirate is then sent for macroscopic and microscopic analysis. This allows both confirmation of gout, as well as the exclusion of other differentials such as septic arthritis and pseudogout.
Under polarized light microscopy, monosodium urate crystals in synovial fluid exhibit negative birefringence. That is, they appear yellow when aligned parallel to the slow axis of red plate compensator, and blue when aligned in the direction of polarization.
NSAIDs and colchicine are the most widely used drugs in the management of acute flares of gout.
NSAIDs exert their effects via their anti-inflammatory properties, whereas colchicine inhibits neutrophil migration from blood vessels into the joint space and interfering with interleukin 1b production, thereby limiting the development of an inflammatory reaction.
Selective COX-2 inhibitors (e.g. celecoxib) are also used in the management of acute gout. Second-line drugs include IL-1 inhibitors and corticosteroids (either oral, intravenous, or intraarticular).
Pharmacologic interventions for acute gout should be started as soon as possible, preferably within 12 hours of the onset of symptoms.
Following resolution of an acute episode of gout, urate lowering therapy may be considered, although this is not required in all patients. Key indications include:
Pharmacologic interventions include the use of xanthine oxidase inhibitors (allopurinol and febuxostat), uricosurics (probenecid, benzbromarone, sulfinpyrazone), or urate oxidases (rasburicase); and stopping hyperuricemic drugs such as thiazide and loop diuretics, beta blockers, and ACE inhibitors. Target serum urate levels are <6mg/dL or <5mg/dL in severe tophaceous gout.
Non-pharmacologic interventions include lifestyle and dietary modifications such as increased physical activity, weight loss, reduced alcohol intake, reduced intake of fructose sweetened sodas, reduced meat and seafood intake, increased hydration, and increased intake of skimmed milk.
If urate lowering measures are embarked on, prophylaxis with low dose NSAIDs or colchicine is important prevent recurrences secondary to urate mobilization and dissolution.
During urate lowering therapy, there is an increased risk of gout flares. This risk can be reduced with low dose NSAID or colchicine therapy. If a flare still occurs, the drug should be upgraded to the treatment dose, and the urate lowering agent continued at the existing dose.