A disease state characterized by recurrent attacks of acute mono or polyarthritis of various peripheral joints which results from deposition of monosodium urate crystals in or about the various joints or tendons. Diseased joints are tender, warm, swollen, and erythematous. Commonly affected joints include the metatarsophalangeal joint of the first toe (podagra is the term used when symptoms manifest at the great toe), knee, wrist, elbow, and the instep of the foot. Associated gouty tophi are may be found on the helix of the ear, ulnar aspect of the forearms, and the hands. Fever may be associated with acute gout flares.
A definitive diagnosis of gout can be made when polarizing microscopy identifies monosodium urate (MSU) crystals in the synovial fluid of affected joints. The diagnosis may be established in the absence of aspirated synovial fluid or in the presence of tophi secondary to uric acid. The diagnosis is suggested when there is a history of prior attacks of acute monoarthritis followed by asymptomatic periods in the presence of hyperuricemia and when acute symptoms resolve rapidly after NSAID or colchicine therapy. Other diseases that need to be considered include septic arthritis, pseudogout (which also responds to colchicine therapy), and Reiters syndrome. Joints which are commonly affected during gout attacks include the midfoot, ankle, first metatarsophalangeal joint (podagra) and the knee. The serum uric acid level is variable during an acute attack and can not be used to "rule out" gout if the level is low. Conversely, many persons suffer from hyperuricemia without gout; therefore, an elevated level in a patient with joint pain does not establish the causes of joint pain as necessarily being secondary to gout.
Acute treatment entails therapy with either high dose NSAIDs, colchicine (1.2 mg bolus then 0.6 mg 1 hour later followed by a BID or TID schedule starting the second day of therapy), oral steroids (prednisone 10-30 mg BID), intraarticular steroids (20-40 mg methylprednisolone) or the interleukin-1 receptor antagonist anakinra (100 mg subcutaneously QDay). Prompt relief with colchicine therapy is characteristic of an acute gouty attack but may also be seen with pseudogout, an arthropathy associated most commonly with calcium pyrophosphate dihydrate crystals. Combination therapy for acute attacks entails colchicine in conjunction with either an NSAID or a steroid. In patients with a past history of gout, do not withhold chronic hyperuricemia therapy during an acute attack. Rather, add acute therapy on top of the xanthine oxidase inhibitor or probenecid.
If patients manifest recurrent gouty attacks in the presence of hyperuricemia, therapy to normalize serum uric acid levels should be instituted. Normalization of serum uric acid levels may be accomplished with allopurinol or febuxostat, or the uricosuric agenst probenecid or sulfinpyrazone.. Therapy to lower serum uric acid levels should only be initiated when patients are free of gouty symptoms. The xanthine oxidase inhibitors are most often used and therapy should be titrated every two weeks to lower uric acid levels to less than 6 mg/dL. Uric acid levels should be lowered slowly as rapid changes in serum levels may cause a flare of gout symptoms. Initially during uric acid lowering therapy, an NSAID or colchicine should be continued to prevent the risk of recurrent gout attacks as uric acid crystals are mobilized. Once the patient's uric acid has normalized for approximately two to six months without symptoms of gout, then the prophylactic NSAID or colchicine may be discontinued unless symptoms return. Pegloticase is an intravenous agent used to lower uric acid levels in cases of tophaceous gout. Whereas diuretics serve to induce gout, the ARB losartan and the lipid lowering agent fenofibrate serve to lower serum uric acid levels and should be considered in gout patients who require treatment with either an ARB or a fibrate.
Before therapy is initiated, a 24-hour urine collection for uric acid determination may be collected if probenecid or sulfinpyrazone therapy are being considered. If patients excrete uric acid in excess of 700 mg/day, then the underlying problem is uric acid overproduction and therapy with a xanthine oxidase inhibitor should be instituted. If the 24-hour urinary uric acid level is low, then decreased renal uric acid excretion is the cause of hyperuricemia and treatment with a uricosuric agent may be appropriate. Uricosuric agents are contraindicated in patients with impaired renal function, a history of nephrolithiasis or if patients have normal or elevated 24 hour urinary uric acid levels. Uricosuric agents are ineffective if given while patients are undergoing NSAID therapy.