Overview and Risk Factors
Gout is a metabolic disease characterized by hyperuricemia and precipitation and tissue deposition of urate crystals, resulting in inflammation and tissue injury. Clinical manifestations include recurrent bouts of acute, often monoarticular arthritis, which most commonly affects the first metatarsophalangeal joint ("podagra"), knees, ankles, and wrists; nephrolithiasis; and palpable tophi.
Ninety percent of cases are due to decreased excretion of uric acid, usually secondary to chronic renal disease, low volume states, and diuretic use. The remaining 10% are due to excess uric acid production, as may occur in the context of inherited enzyme abnormalities, psoriasis, hemoglobinopathies, and leukemias. Not all patients with hyperuricemia will develop gout. Indeed, about two-thirds of hyperuricemic patients will remain asymptomatic. Higher levels of serum uric acid and longer durations of exposure increase the risk of progression to clinical disease. However, some patients with clinical symptoms of gout have normal serum uric acid levels.
- Age. Incidence increases with age.
- Gender. In younger populations, gout occurs more commonly in males, presumably because estrogen facilitates urinary excretion of urate in women. Gender does not affect risk in older patients.
- Family history.
- Dietary factors. See Nutritional Considerations below.
- Medication. Diuretics, cyclosporine, aspirin, and niacin increase serum uric acid levels.
- Stress, trauma, surgery. These factors may precipitate acute attacks.
Diagnosis and Treatment
Signs and symptoms consistent with acute monoarticular arthritis suggest gout. However, definitive diagnosis requires demonstration of urate crystals in joint or tophus aspirate.
Elevated serum uric acid level is present in most cases.
Synovial fluid aspirate reveals negatively birefringent, needle-shaped crystals, or tophi aspirate reveals urate crystals.
A 24-hour urine uric acid collection may help distinguish overproduction from underexcretion (>800 mg of uric acid/24 hours indicates overproduction).
Early in the disease, x-rays of the joints may appear normal. As the disease progresses, punched-out erosions with a rim of cortical bone may appear.
Treatment of asymptomatic hyperuricemia is usually not indicated, aside from the dietary adjustments noted below in Nutritional Considerations. Anti-inflammatory agents for acute attacks and prophylaxis for patients with high risks of recurrence are the cornerstones of therapy.
The treatment of choice for acute attacks in otherwise healthy adults is bed rest and nonsteroidal anti-inflammatory drugs (NSAIDs); indomethacin is often used.
Corticosteroids are reserved for severe disease or in patients who cannot take NSAIDs (eg, patients with renal failure). Monoarticular disease may be treated with intra-articular steroid administration. Polyarticular gout may be treated with oral or IV steroids.
Due to the high incidence of side effects, colchicine is now used less commonly than in the past.
Prophylactic medications to reduce the risk of further attacks include allopurinol, which inhibits xanthine oxidase and decreases urate production, and probenicid, which decreases renal uric acid reabsorption.
Surgery is reserved for severe cases, including joint deformities, intractable pain, and nerve compression due to tophi.
Gout is significantly influenced by diet. A high intake of meat, for example, is a known risk factor for the elevated uric acid level that is associated with gout. Gout occurs more commonly in overweight persons, particularly those with metabolic syndrome (see Obesity).
The following factors are associated with decreased risk of gout:
Reducing or avoiding meat. Studies have found that, compared with persons eating the least red meat, poultry, or fish, those eating the highest amount have higher uric acid levels and a significantly greater risk for developing gout.1,2
Weight control. After adjustment for uric acid level, body mass index independently predicts gout risk.3 Compared with men at or near their ideal weight, overweight men (BMI of 25 to 29.9) have almost double the risk for developing gout. Risk is nearly tripled for those with a BMI of 35 or greater.4
Avoidance of alcohol. Serum uric acid is associated with alcohol intake in men.5 With the possible exception of moderate wine intake, the risk for gout appears to increase linearly with alcohol consumption.6
In addition, the following diet and lifestyle considerations should be noted:
Elevated lead levels. Elevated body lead burden increases serum uric acid and can compromise kidney function,7 although evidence for a connection between lead exposure and the development of gout has not been established.8 Lead exposure in adults can occur through many mechanisms, notably occupational exposures, storage of alcoholic beverages in lead crystal, and lead piping in older homes. For further details, see the Foodborne Chemicals chapter. Chelation treatment to remove lead results in improved clearance of uric acid from the blood.9
Kidney stones. Gout appears to increase the risk for kidney stones,10 and consuming 2 liters or more of water and water-based beverages per day may be helpful in reducing the risk of stone formation in gout patients.11 (See also Nephrolithiasis.)
Cherry consumption. An intriguing but unconfirmed report found that consuming roughly 9 ounces of bing cherries (280 g, or 45 cherries) daily was associated with a significant reduction in blood uric acid concentrations. Postulated mechanisms include an increase in the rate of renal glomerular filtration, reducing tubular reabsorption of uric acid, and anti-inflammatory effects.12
What to Tell the Family
Gout is a treatable disease that often responds well to a combination of diet therapy and medication. Loss of excess weight may enhance treatment by improving the kidney's ability to clear uric acid from plasma. Avoidance of alcohol and meat is important for lowering blood levels of uric acid and may also reduce the symptoms of metabolic syndrome that often accompany elevated uric acid.
1. Choi HK, Liu S, Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2005;52:283-289.
2. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004;350:1093-1103.
3. Lin KC, Lin HY, Chou P. Community-based epidemiological study on hyperuricemia and gout in Kin-Hu, Kinmen. J Rheumatol. 2000;27:1045-1050.
4. Choi HK, Atkinson K, Karlson EW, Curhan G. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the Health Professionals' Follow-Up Study. Arch Intern Med. 2005;165:742-748.
5. Loenen HM, Eshuis H, Lowik MR, et al. Serum uric acid correlates in elderly men and women with special reference to body composition and dietary intake (Dutch Nutrition Surveillance System). J Clin Epidemiol. 1990;43:1297-1303.
6. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: a prospective study. Lancet. 2004;363:1277-1281.
8. Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H. Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study. J Rheumatol. 2000;27:1708-1712.
10. Kramer HJ, Choi HK, Atkinson K, Stampfer M, Curhan GC. The association between gout and nephrolithiasis in men: The Health Professionals' Follow-Up Study. Kidney Int. 2003;64:1022-1026.
11. Asplin JR. Uric acid stones. Semin Nephrol. 1996;16:412-424.
12. Jacob RA, Spinozzi GM, Simon VA, et al. Consumption of cherries lowers plasma urate in healthy women. J Nutr. 2003;133:1826-1829.