1. Patient education. It is important that the patient realize that gout is a chronic disease and that certain life-style modifications, such as maintenance of an ideal weight and moderation of alcohol intake, are important. A purine-restricted diet may be of benefit in some patients, but only small changes in serum uric acid can be attained. Other factors worth emphasizing are ingestion of at least 2 L of fluids daily to help prevent renal stones and avoidance of alcohol and low-dose aspirin, which aggravate hyperuricemia.
2. Drug therapy. The goals of therapy are to prevent renal parenchymal damage and nephrolithiasis and to suppress articular flares. Drug strategy in chronic gout is determined by the pattern of 24-hour urate excretion and the severity of disease.
a. Colchicine prophylaxis. Colchicine (0.6 mg daily or twice daily) is effective in diminishing the frequency and severity of spontaneous gout flares and flares induced by initial allopurinol and probenecid therapy. Colchicine may be discontinued after a 6-month symptom-free interval if allopurinol or probenecid has been started. Otherwise, it is continued indefinitely. In the elderly and those with impaired renal function, the dose is 0.6 mg daily. In dialysis patients, oral colchicine is generally best avoided. Some clinicians have abandoned long-term colchicine prophylaxis for several reasons. First, colchicine does not lower urate levels or prevent tophi. Second, acute attacks can be handled as described in section IILD.,. and oral colchicine at times can cause toxicity, including bone marrow suppression and myopathy. Third, no randomized controlled studies are available to demonstrate the benefit of colchicine alone as a preventive agent in interval gout.
b. Recurrent gout attacks are treated as described earlier (see section..III.D). The patient may be given a supply of indomethacin (the drug of choice for acute attacks) with instructions to take 50 mg q6h at the first sign of a gout prodrome and to call the physician. When indomethacin is self-administered in this manner, a gout attack may be aborted with only two to three doses.
c. Uricosurics. The goal is to lower urate to approximately 6.0 mg/dL (auto-analyzer measurement). Most commonly, these drugs are used in patients less than 50 years of age.
1. Indications (all must be present)
b. Normal renal function.
c. Absence of tophi.
d. No history of renal calculi.
2. Administration. Prophylactic colchicine (0.6 mg twice daily) should begin 3 days before therapy. Probenecid is the uricosuric drug of choice. The initial dosage is 250 mg twice daily for 1 week. The dosage is increased to 500 mg two to three times daily depending on serum uric acid response. Adequate hydration must be maintained to prevent uric acid precipitation in renal tubules.
d. Allopurinol. The goal is to lower urate to approximately 6.0 mg/dL.
1. Indications (only one need be present)
a. Hyperexcretion of urate (>800 mg/24 h).
b. History of renal calculi.
d. Renal insufficiency and gout.
e. There is another indication for lowering urate, and uricosuric drugs are ineffective, not tolerated, or contraindicated.
f. Before cytotoxic therapy for neoplasia.
g. Continued attacks of gout despite colchicine prophylaxis, uricosuric drugs, or both. The severity of the gout attacks and the presence of radiographic joint damage are taken into consideration in the individual case.
2. Administration. Prophylactic colchicine (0.6 mg twice daily) can be started 3 days before initiation of allopurinol therapy. Some clinicians avoid oral colchicine in this setting and treat any flares of gout with NSAIDs or corticosteroids. Colchicine is appropriate for patients in whom prevention of gouty attacks during the initiation of the allopurinol therapy is felt to be especially important. When colchicine prophylaxis is used in this setting, it is generally continued for 6 months. The initial allopurinol dosage is 100 mg daily, which is increased weekly until the maintenance dosage of 300 mg daily is reached. Dosages as high as 600 to 800 mg/d may be needed in a few patients to achieve clinical control. If the creatinine clearance is less than 20 mL/min, the toxicity (skin rash, vasculitis, agranulocytosis) of allopurinol increases. The dosage of allopurinol is decreased according to decreased renal function. For a glomerular filtration rate of 20 to 30 mL/min, the dose of allopurinol should be reduced to 100 mg/d.
3. Allopurinol allergy. Oxypurinol (an active metabolite of allopurinol) has been shown to be as effective as allopurinol and can be used (by special release from the manufacturer) in patients with allopurinol allergy. However, cross-reactive allergy has occurred in as many as 50% of cases. IV and oral desensitization regimens for allopurinol have been published.
e. Joint aspiration and intraarticular injection of corticosteroid preparations may be indicated for patients with persisting chronic synovitis. The technique and dosage regimen are described in Chapter.4.
f. Prevention of nephrolithiasis. In patients with renal stones, the following measures may be used.
1. Urine alkalinization. A urine pH greater than 6.0 can be achieved with one of the following:
a. Sodium or potassium citrate (Polycitra) (20 mL four times daily). However, compliance with a regimen of dosing four times daily is difficult.
b. Acetazolamide (500 mg at bedtime).
2. Large urine volume. The patient should be instructed to drink adequate fluids to produce at least 2 L of urine daily.
g. Surgical therapy. Surgical removal of large tophi is indicated if they become infected or interfere with joint function.
VII. The prognosis of properly managed gout is excellent, and most patients have a normal life span. Chronic deforming arthritis and periarthritis can occur in long-standing untreated cases. In rare patients with severe tophaceous renal disease, chronic renal failure may develop.
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