Rationale:

• Few patients with hyperuricemia develop gout. Potential reactions to medications may outweigh benefits because hypersensitivity reactions to allopurinol may be fatal.

Evidence:

• The Framingham Study (4) showed that 4.8% of women and 9.3% of men may have uric acid levels > 7 mg/dL over time (if tested on several occasions); 81% of patients with uric acid levels > 7 mg/dL on screening never developed gout. Of patients with gout, 29% had a normal uric acid level on initial screening.
• The Normative Aging Study (5) followed 2046 healthy men for a mean of 14.9 years through the Boston Veterans Administration Medical Center. The incidence of gout was three times higher among hypertensive patients.
• The National Health and Nutrition Examination Survey III showed an independent association of nephrolithiasis and gout; after adjustment for race, sex, BMI, and hypertension, those with gout had an odds ratio of 1.49 for the development of kidney stones (6).
• In a study using an administrative claims database to study trends in prevalence of gout among different age groups, the prevalence of gout and/or hyperuricemia increased from 2.91 to 5.23 cases per 1000 enrollees over a 10-year period. The prevalence was progressively higher in older age groups and increased from 20.55 to 41.28 cases per 1000 enrollees in persons over age 75 (7).
• Patients with familial gout have been found to have disease onset 7.5 years earlier than that of nonfamilial cases and were less dependent upon dyslipidemia and hypertension effects (8).
• A review of allopurinol toxicity showed that most patients with allopurinol toxicity took 200 to 400 mg/d and had concomitant renal insufficiency; many had been treated for asymptomatic hyperuricemia (9).
• One review examined the records of 8 patients with allopurinol hypersensitivity syndrome and an additional 72 patients described in the literature (10).

Comments:

• Uric acid level has been shown to be a risk factor for cardiovascular and all-cause mortality; however, this has not been shown to be a modifiable risk factor, and treatment of asymptomatic hyperuricemia is still not recommended (11).