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.

Risk Factors

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.

Obesity.

Medication. Diuretics, cyclosporine, low-dose aspirin, and niacin increase serum uric acid levels.

Stress, trauma, surgery. These factors may precipitate acute attacks.

Diagnosis

Signs and symptoms consistent with acute monoarticular arthritis suggest gout. However, definitive diagnosis requires demonstration of intracellular monosodium urate crystals in a synovial fluid or tophus aspirate.

Elevated serum uric acid level is present in most cases.

In gout, synovial fluid aspirate reveals negatively birefringent, needle-shaped 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.

Imaging technologies, including dual energy CT, MRI, and ultrasound, are particularly helpful for monitoring disease treatment. Dual energy CT may also be helpful with diagnosing disease, although it should not replace joint aspiration.[1]

Treatment

Treatment of asymptomatic hyperuricemia, aside from the dietary adjustments noted below in Nutritional Considerations, is usually not indicated. Anti-inflammatory agents for acute attacks and prophylaxis for patients with high risk 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 for patients who cannot take NSAIDs (e.g., 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.

Prophylactic medications to reduce the risk of further attacks include allopurinol, which inhibits xanthine oxidase to decrease uric acid production, and probenecid, which increases uric acid excretion. Caution must be exercised with the use of probenecid because it may increase the risk for nephrolithiasis. Rarely, allopurinol may cause Stevens-Johnson syndrome.

Febuxostat is a nonpurine inhibitor of xanthine oxidase that may be useful in patients with renal insufficiency because it is metabolized in the liver. Its use is associated with sustained lowering of serum uric acid, reduction of gout flares, and reduction of tophus area.[2] Retrospective studies suggest better efficacy and faster rate of improvement of serum uric acid levels compared with allopurinol, although the cost of febuxostat is often a limiting factor.[3]

Losartan lowers uric acid levels by virtue of direct inhibition of URAT1 (urate anion exchanger).[4] This angiotensin-receptor blocker (ARB) is uricosuric at 50 mg/day and might be an ideal choice in patients requiring treatment for concomitant hypertension. Low-dose aspirin is also uricosuric, but its effects are very mild.[5]

Lesinurad (Zurampic) is the first selective uric acid reabsorption inhibitor (SURI) approved by the FDA, receiving approval in 2015. It acts by inhibiting the urate transporter, URAT1, which is responsible for the majority of renal uric acid reabsorption. Lesinurad must be co-administered with a xanthine oxidase inhibitor and is for hyperuricemia with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.[6]

Surgery is reserved for severe cases, including joint deformities, intractable pain, and nerve compression due to tophi.

Pegloticase is a pegylated enzyme that catalyzes the breakdown of uric acid to allantoin. It is highly effective, particularly in tophi reduction, but is expensive and has a potential for severe adverse reactions, including infusion-related reactions despite premedication, so it is reserved for severe, refractory gout.[7] ,[8]

Nutritional Considerations

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 chapter).

The following factors are associated with decreased risk of gout:

Replacing meat with legumes and other plant proteins. Evidence has become clearer that protein intake per se is not responsible for elevating uric acid levels and causing gout. Animal protein in the form of meat in particular does however contribute to both of these, while plant protein (even those containing purines) does not raise uric acid or gout risk.[9] Certain purines are less likely to yield uric acid during metabolism than others; this may explain the findings of epidemiological and clinical studies on soy and other legumes, which universally reveal a decrease in risk for gout with higher levels of consumption.[10] In addition, many flavonoids found in legumes and othe plant foods inhibit xanthine oxidase.[11]

Maintenance of healthy body weight. The risk for developing gout increases with body weight in a linear fashion. Compared with persons at a BMI of 20, the risk for individuals with a BMI of 25, 30, 35, and 40 were 78%, 267%, 362%, and 464% higher, respectively.[12]

Avoidance of alcohol. Ethanol metabolism results in ATP degradation, resulting in purine release and an increase in uric acid. While this effect has been attributed to ethanol per se, the effect is most pronounced with beer (a 250% increase for daily consumption of two servings of beer compared to none), less with liquor (a 60% greater risk for one daily serving of liquor), and unclear with regard to wine intake.[7]

Avoidance of sugar-sweetened beverages. Fructose, which is found in the high fructose corn syrup commonly used by soda manufacturers, is the only carbohydrate known to increase uric acid levels. Acting through purine nucleotide degradation or de novo purine synthesis, high amounts of fructose can also lead to insulin resistance. This in turn decreases renal excretion of uric acid. Although some data indicate a nearly two-fold risk for gout when consuming two or more servings of sugar-sweetened drinks per day (compared with less than one serving/month), other evidence has suggested that uric acid levels increase only when individuals consume very high amounts of fructose.[7]

In addition, the following diet and lifestyle considerations should be noted:

Elevated lead levels. In t he National Health and Nutrition Examination Survey (NHANES 2005-2008), individuals in the highest quartile for blood lead levels had a 3.6-fold higher risk for gout, compared with those in the lowest quartile.[13] 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 Foodborne Chemicals chapter.)

Kidney stones. Gout appears to increase the risk for kidney stones,[14] 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.[15] (See also Nephrolithiasis chapter.)

Dairy intake. Dairy protein has both a uricosuric and anti-inflammatory effect that are thought to be involved in the reduced risk for gout associated with the intake of dairy products.[7] However, these protective effects need to be considered in the context of associations between dairy intake and a significantly increased risk for other diseases (see Parkinson Disease and Prostate Cancer chapters).

A high vitamin C intake. A meta-analysis of randomized controlled trials found that vitamin C supplements (median dosage 500 mg/d) significantly reduce uric acid levels.[16] In the Health Professionals Follow-Up Study, the risk for gout decreased in a linear fashion with supplemental vitamin C intakes of 500-999 mg/d, 1000-499 mg/d, and 1500 mg/d or more, compared with men whose intakes were 250 mg/d or less.[17]

Orders

See Basic Diet Orders Chapter

Low-purine diet recommended.

Alcohol restriction.

Weight loss if indicated.

What to Tell the Family

Gout is a treatable disease that often responds well to a combination of diet therapy and medication. The family can help the patient in adhering to a healthful diet and can be most supportive by adopting the same dietary changes as the patient. 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. Loss of excess weight may enhance treatment by improving the kidney’s ability to clear uric acid from plasma.

References

  1. McQueen FM, Reeves Q, Dalbeth N: New insights into an old disease: advanced imaging in the diagnosis and management of gout. Postgrad Med J 89:87, 2013  [PMID:23112219]
  2. Gelber AC: Febuxostat versus allopurinol for gout. N Engl J Med 354:1532, 2006  [PMID:16602151]
  3. Singh JA, Akhras KS, Shiozawa A: Comparative effectiveness of urate lowering with febuxostat versus allopurinol in gout: analyses from large U.S. managed care cohort. Arthritis Res Ther 17:, 2015  [PMID:25963969]
  4. 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 52:283, 2005  [PMID:15641075]
  5. Qaseem A et al: Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 166:58, 2017  [PMID:27802508]
  6. Zurampic (lesinurad) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2015.
  7. Gentry WM et al: Investigation of pegloticase-associated adverse events from a nationwide reporting system database. Am J Health Syst Pharm 71:722, 2014  [PMID:24733135]
  8. Becker MA et al: Long-term safety of pegloticase in chronic gout refractory to conventional treatment. Ann Rheum Dis 72:1469, 2013  [PMID:23144450]
  9. MacFarlane LA, Kim SC: Gout: a review of nonmodifiable and modifiable risk factors. Rheum Dis Clin North Am 40:581, 2014  [PMID:25437279]
  10. Messina M, Messina VL, Chan P: Soyfoods, hyperuricemia and gout: a review of the epidemiologic and clinical data. Asia Pac J Clin Nutr 20:347, 2011  [PMID:21859653]
  11. Spanou C et al: Flavonoid glycosides isolated from unique legume plant extracts as novel inhibitors of xanthine oxidase. PLoS ONE 7:, 2012  [PMID:22396752]
  12. Aune D, Norat T, Vatten LJ: Body mass index and the risk of gout: a systematic review and dose-response meta-analysis of prospective studies. Eur J Nutr 53:1591, 2014  [PMID:25209031]
  13. Krishnan E, Lingala B, Bhalla V: Low-level lead exposure and the prevalence of gout: an observational study. Ann Intern Med 157:233, 2012  [PMID:22910934]
  14. Kramer HJ et al: The association between gout and nephrolithiasis in men: The Health Professionals' Follow-Up Study. Kidney Int 64:1022, 2003  [PMID:12911552]
  15. Wiederkehr MR, Moe OW: Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder. Clin Rev Bone Miner Metab 9:207, 2011  [PMID:25045326]
  16. Juraschek SP, Miller ER, Gelber AC: Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken) 63:1295, 2011  [PMID:21671418]
  17. Choi HK, Gao X, Curhan G: Vitamin C intake and the risk of gout in men: a prospective study. Arch Intern Med 169:502, 2009  [PMID:19273781]

Last updated: November 21, 2017

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TY - ELEC T1 - Gout ID - 1342063 Y1 - 2017/11/21/ PB - Nutrition Guide for Clinicians UR - https://nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342063/all/Gout ER -