Gout - Treatments for Gout
Acute episodes are treated with NSAIDs. Ibuprofen 800 mg three to four times daily or Indomethacin 25 to 50 mg four times daily are often chosen because of their quick onset of action, but most NSAIDs can be used. The new selective COX-2 inhibitors (celecoxib, rofecoxib) should work as well, but have not been formally tested in controlled trials. Treatment should be discontinued when symptoms resolve.
In patients with contraindications to NSAID use, corticosteroids are the next choice. Intra-articular steriods are useful if only one or two joints are affected and the treating physician is proficient in injecting those joints. Oral prednisone can be used starting at 30-40 mg daily tapering over 10-14 days. Hospitalized patients can be given equivalent doses of corticosteroids intravenously.(ref 2)
Use of high dose colchicine either orally or IV is discouraged except in rare instances. High dose oral colchicine (1.2 mg followed by 0.6 mg every hour for 6 doses) is poorly tolerated because of GI side effects. IV colchicine (2 mg IV then 1 mg in 12 hours) is associated with serious toxcities including myopathy, neuropathy and aplastic anemia.(ref 3, 4)
Because the initial attacks of gout are infrequent, self-limited and easily treated, chronic therapy is usually not indicated. Certainly chronic therapy after the first attack is not warranted. Many patients will have a long duration between attacks as shown in the following table:(ref 5)
| Duration between initial attack and second attack | % Patients |
|---|---|
| 1 year | 62% |
| 1-2 years | 16% |
| 2-5 years | 11% |
| 5-10 years | 6% |
| no reccurrance in 10 years | 7% |
Over time, the attacks of gout become more frequent. When attacks occur several times per year, prophylactic colchicine 0.6 mg daily or bid can be used early in the course of gout to prevent acute gout attacks but should not be used alone without uric acid lowering agents in the presence of tophi or chronic arthritis. In early gout, prophylactic colchicine may be chosen over uric acid lowering agents to prevent gout attacks because of its ease of use and low toxicity.(ref 6)
Treatments: Uric Acid Lowering Therapy
Indications
Foods High in Purines
Medication Options
Use of uric acid lowering agents will reduce the frequency of gout attacks and over time, reduce tophi formation and diminish the risk of joint destruction. The following are indications for uric acid lowering therapy:
- tophi or chronic arthritis on exam
- failure of colchicine prophylaxis of acute gouty arthritis
- renal stones
- Prior to chemotherapy as prophylaxis of tumor lysis syndrome
- Extremely high levels of serum uric acid (>12 mg/dl)
Uric acid is the end product of purine (nucleic acid component of DNA) metabolism and is produced normally by the body during tissue remodeling and breakdown. About 20% of uric acid is derived from purines ingested in food. Causes of hyperuricemia can be divided into two major categories: decreased clearance of uric acid from the kidney and increased synthesis of uric acid.(ref 7)
Decreased renal clearance - (90% of patients)
- Intrinsic kidney disease
- heart disease causing decreased blood flow to the kidney
- drugs (loop diuretics, low dose aspirin, cyclosporin)
- genetic predisposition
- age related decrease in glomerulofiltration rate
Increased uric acid synthesis
- Dietary indiscretions
- Genetic predisposition
- Increased tissue turnover--tumors, lymphoproliferative disorders
- Stress induced increased turnover of ATP
- Alcohol induced turnover of ATP
All patients should be encouraged to modify their lifestyle including limiting alcohol intake, encouraging weight loss where appropriate and decreasing food rich in purines. Co-morbid medical conditions should also be controlled including hypertension, diabetes and hyperlipidemia. Unfortunately, compliance is often poor with this approach.
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- Very High - Hearts, herring , mussels, yeast , smelt, sardines, sweetbreads
- Moderately High - Anchovies, grouse,mutton, veal, bacon, liver salmon, turkey, kidneys, partridge, trout, goose, haddock, pheasant, scallops
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Two choices are available to lower serum uric acid levels.(ref 8) Probencid can be given to patients with decreased clearance of uric acid from the kidney. Patients must have documented decrease in urine uric acid and have a creatinine clearance >40 cc/min. Allopurinol can be used in patients who either have decreased clearance of uric acid or elevated synthesis of uric acid.
Allopurinol
- xanthine oxidase inhibitor
- prevents production of uric acid
- useful in both patients with increased synthesis and decreased clearance of uric acid
- no 24 hour urine needed
- can be used in renal failure
- rarely associated with bone marrow suppression, hepatotoxicity, and hypersensitivity reactions
Although 90% of patients with hyperuricemia have decreased clearance of uric acid, many have poor renal function. Patients are often poorly compliant with requests for 24 hour urine samples. Thus, my and the majority of physicians' approach is to use allopurinol in most cases. Allopurinol is started at 100 mg daily (100 mg qod if creatinine clearance < 10 cc/min) and is titrated by 100 mg every 10-14 days to achieve a serum uric acid level of 4-5 mg/dl. The maximum dose of allopurinol is 800 mg daily. Liver transaminases, complete blood counts and renal function and should be monitored. Toxicites include rash, hepatoxicity, bone marrow suppression and severe hypersensitivity reactions. There are desensitization protocols for allopurinol allergic patients.(ref 9) Allopurinol can raise the levels of warfarin and theophylline and levels should be monitored. Its use in patients on azathiprine, 6-mercaptopurine and cyclophosphamide should be either avoided or used with intensive monitoring for bone marrow toxicity. Initiation of allopurinol can prolong an acute attack of gout if started during the attack, or trigger a gout attack due to shifts in uric acid levels. It is useful to give prophylactic colchicine when starting allopurinol and warn the patient about the possibility of a flare.
Probenecid
- uricosuric
- decreases uric acid reabsorption at the proximal renal tubules
- useful in patients with decreased renal clearance of uric acid
- can only be used if creatinine clearance >40 cc/min
- must have 24 hour urine for uric acid <800 mg/dl
- can be used in renal failure
- increased risk of renal stones
Probenecid may be given to patients with decreased clearance of uric acid by the kidney and normal renal function. In general its use should be limited to patients under the age of 60. Probenecid acts by inhibiting reabsorption of uric acid in the proximal tubules of the kidney. Starting dose is at 500 mg to 1000 mg daily and increased to 1500 mg to 2000 mg as needed. Occasionally higher doses are needed. Probenecid may precipitate renal stone formation and good oral hydration should be encouraged. Probenecid is contraindicated in patients with renal stones (including calcium and uric acid stones) and in patients with urate nephropathy. Probenecid given inappropriately to patients with hyperuricemia due to overproduction of uric acid can cause renal stones and urate nephropathy.
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Tumor Lysis
Patients undergoing chemotherapy may experience a dramatic rise in serum uric acid levels associated with lysis of the tumor mass. Such large increases in uric acid can deposit in the renal tubules causing renal failure or nephrolithiasis. Allopurinol is often given prophylactically prior to chemotherapy.
Interstitial Renal Deposition
Patients with prolonged hyperuricemia may deposit uric acid in the renal interstitium. With moderate levels of hyperuricemia (<11 mg/dl), this has little clinical signficance in terms of renal outcome. However, in patients with severe elevations in uric acid, ›12 mg/dl, use of allopurinol should be considered.
Renal Stones
Hyperuricemia increases risk for both calcium and uric acid renal stones. Allopurinol is the treatment of choice.
1. Campion EW, Glynn RJ, deLabry LO. Asymptomatic Hyperuricemia Risks and Consequences. Am J Med 82:421, 1987.
2. Groft GD, Franck WA, Raddarz DA. Systemic Steroid Therapy for Acute Gout: A clinical trial and review of the literature. Semin Arthritis Rheum 19:329, 1990.
3. Roberts WN, Liang MH, Stein SH. Colchicine in Acute Gout Reassessment of Risks and Benefits. JAMA 257:1920, 1987.
4. Wallace SL, Singer JZ. Review: Systemic Toxicity Associated with Intravenous Administration of Colchicine--Guidelines for Use. J Rheumatol 15:495, 1988.
5. Gutman AB. Gout. Textbook of Medicine. 12th ed., Beeson PB and McDermott W (eds), Philadelphia: W. B. Saunders, 1958, p 595.
6. Paulus HE, Schlosstein LH, godfrey RL, et al. Prophylactic Colchicine Therapy of Intercritical Gout. A placebo-controlled study of probenecid-treated patients. Arthritis Rheum 17:609, 1987.
7. Kelly WN, Wortmann RL. Gout and Hyperuricemia. Textbook of Rheumatology. 5th ed., Kelly WN, Harris ED Jr., Ruddy S, Sledge CB (eds), Philadelphia: W. B. Saunders, 1997, p 1313-1347.
8. Emmerson BT. The Management of Gout. N Engl J Med 344:445, 1996.
9. Halz-LeBlanc BAE, Reynolds WJ, MacFadden DK. Allopurinol Hypersensitivity in a Patient with Chronic Tophaceous Gout: Success of intravenous desensitization after failure of oral desensitization. Arthritis Rheum 34:1329, 1991.
