Treatment of Gout and Hyperuricemia

Treatment of gout specifically addresses one of three clinical entities: (1) acute gout, (2) the intercritical period that occurs for 2 to 3 months after an acute attack, or (3) long-term management of chronic hyperuricemia.

Treatment of Acute Gout

Attacks of acute gout are most commonly managed by nonsteroidal antiinflammatory drugs (NSAIDs) (see Chapter 4). High doses are needed. Although all NSAIDs are probably effective for acute gout,

Gout Radiographs Lumbar Spine
Fig. 9.1. Radiograph of the hand of a patient with gout. There are typical margin erosions and areas of radiolucency at the proximal interphalangeal joints of the index and long fingers bilaterally.

indomethacin (Indocin) is commonly used. One regimen involves giving indomethacin 50 mg four times a day for the first 2 days, then 50 mg three times a day for a week, then 50 mg twice a day for a week, then 25 mg two or three times a day for 2 to 3 weeks (or more). Acute gout can also be treated with colchicine in a dose of 0.6 mg/hr by mouth up to a total of 5 or 6 mg until relief or severe gastrointestinal side effects occur. At one time it was thought that colchicine was effective only for acute gouty arthritis, and so its use had utility in the differential diagnosis; it is now known that colchicine is at times successful for any form of acute arthritis.15 Colchicine can be given intravenously, a method that reduces side effects; but the drug is potentially toxic in this form, and it is recommended that physicians considering the use of intravenous colchicine carefully review the instructions for its use.16 For patients who are unlikely to tolerate treatment with NSAIDs or colchicine (e.g., those with gastrointestinal disease or renal failure), intraarticular or even systemic steroids can be used. Another option is the use of a single dose of 60 mg of depo-triamcinolone (Kenalog) intramuscularly.17 Adrenocorticotropic hormone (ACTH) is also effective in a dose of 0.4 mg (40 units) IM, which may have to be repeated every 12 hours for 2 to 3 days.13,18

Management of Intercritical Gout

Patients who have had resolution of an acute gouty attack are susceptible to a recurrence in the same joint for the next 2 to 3 months, a period known as the intercritical period. Hence, preventive therapy is indicated for several months after an acute attack. Oral colchicine at 0.6 mg one or two times a day is effective for this purpose and is unlikely to have any side effects. Low-dose colchicine can be started along with NSAIDs at the time of an acute attack. Another alternative is low-dose NSAID therapy, such as indomethacin 25 mg twice a day, though this alternative is more likely to cause side effects.

Hypouricemic agents (e.g., allopurinol or probenecid) worsen an acute gouty attack and are never used during one. After some weeks of intercritical treatment the possibility of starting chronic drug therapy to lower the serum uric acid level can be considered. In patients who have only an occasional gouty attack and have no complication of gout such as tophi or gouty renal disease (see section below), treatment of hype-ruricemia is optional; some patients prefer the risk of an occasional attack to taking medicine on a long-term basis. Patients who believe their attacks are frequent enough to justify treatment or in whom treatment is indicated because of tophi or gouty renal disease should undergo treatment directed at hyperuricemia. Most experts believe that dietary therapy is of marginal benefit in lowering uric acid levels,19 although patients should be advised to lose weight and reduce consumption of alcohol, meats, fat, and cholesterol. Hydration is important. Avoidance of medications that elevate the serum uric acid level is also helpful. Low-dose aspirin, niacin, and diuretics are the most common of these agents, and cyclosporine is another offender.


Medical treatment of hyperuricemia involves use of either uricosuric agents or allopurinol (Zyloprim), an agent that interferes with uric acid metabolism. The choice of agent depends on patient characteristics. Allopurinol is indicated in patients with nephrolithiasis, tophi, or renal disease. It is also indicated in patients with congenital overproduction of uric acid. These patients can be identified by collecting a 24-hour urine specimen for uric acid assay; the uric acid content is more than 1 g in overproducers (some clinicians use 600 or 800 mg as the cutoff).

Patients with hyperuricemia who excrete less than 1 g/24 hr are considered to be underexcreters and can be treated with a uricosuric agent instead of allopurinol unless they have nephrolithiasis, tophi, or renal failure. Probenecid (Benemid), the most commonly used uricosuric agent, is started at 250 mg twice a day for a few days, then increased to 500 mg twice a day, and gradually increased up to a total of 3 g/day if needed. The goal of therapy is to get the serum uric acid below 6.0 mg/dL (360 ^mol/L), although a level of 5 mg/dL (300 ^mol/L) or less more effectively dissolves uric acid crystals. Gastric intolerance to probenecid is fairly common, and many drug interactions occur; for example, aspirin eliminates the uricosuric effect of probenecid. The cost of probenecid is also slightly higher than that of allopurinol. For this reason, many clinicians prefer to use allopurinol even in underex-creters. It is effective against any form of hyperuricemia.

Allopurinol should be started at a dose of 100 mg/day and increased gradually up to 300 mg/day if needed to keep the serum uric acid under 6.0 mg/dL (360 ^mol/L). If the serum uric acid remains elevated in a patient on allopurinol 300 mg/day, noncompliance should be suspected,20 although doses up to 800 mg/day are occasionally needed. The most common side effect of allopurinol is a rash; a vasculitic syndrome affecting the skin and kidneys accompanied by fever, leukocytosis, eosinophilia, and hepatitis may be seen. This syndrome is more common among the elderly and in patients with renal failure or on diuretic therapy; in these patients use of the lowest possible dose of allopurinol and a goal of 7 mg/dL (420 ^mol/L) rather than 6 mg/dL (360 ^mol/L) can be considered. When this syndrome occurs, it is treated with high-dose steroids.

Acute attacks of gout are common when either uricosuric agents or allopurinol are started, even if several months have elapsed since the patient's last attack. It is important to warn patients of this possibility. Continuing prophylactic therapy with colchicine at 0.6 mg once or twice a day for the first year of hypouricemic therapy is advised. Starting with low doses of hypouricemic agents, as noted above, is also helpful. Urate-lowering drugs should not be started until a month has passed since the last acute attack of gout, and, if possible, colchicine should be started first and continued for the first few months of treatment with urate-lowering therapy, although the risk of possible toxicity to colchicine needs to be considered.13

Finally, patient education is an important component in the management of gout. Patients need to understand the difference between the agents used to control acute gout, the intercritical period, and chronic therapy with urate-lowering agents, or there will be substantial confusion and worsening of their condition.20 Patients need to be followed regularly by the same provider with frequent monitoring of their uric acid levels for those on urate-lowering therapy; patient education can occur during these visits.

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  • lachlan
    What happens in the body when acute attack of gout occurs in a patient with hyperuricemia?
    7 months ago

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