Gout: Treatment Considerations for the Practicing Pharmacist

Gouty arthritis, or simply gout, is one of the most painful of the >100 arthritic conditions. It accounts for 5% of arthritis cases, affecting mostly people of European and North American descent¹ (see box^1-4).

Approximately 75% of gout cases involve the large toe, but the instep, ankles, heels, knees, wrists, fingers, and elbows also may be affected. Attacks often occur at night when synovial effusions lessen and urate diffuses more slowly across synovial membranes, facilitating sodium urate crystal deposits around joints.^2,5,6

Often, decreased renal uric acid (UA) clearance causes UA buildup, which leads to urate crystal formation. Gout may be primary, attributable to inborn purine metabolism deficits, or secondary, attributable to underlying disorders (eg, myeloproliferative disorders, polycythemia vera, sarcoidosis) or drugs.^1,3,4 Gout, for example, develops in 10% of organ transplant recipients treated with cyclosporine.⁷

Four stages in the progression of gout are as follows:

1. Asymptomatic hyperuricemia occurs when serum UA levels generally exceed 7 mg/dL, but patients remain asymptomatic and may (or may not) progress to acute gout.

2. Acute gouty arthritis occurs when needle-shaped urate crystal deposits in joint spaces cause inflamed, swollen, and warm joints. Attacks usually subside within 10 days, but over time they escalate in frequency and duration. There is ~60% recurrence within the first year.

3. Intercritical gout is the period between attacks when joint function is normal.

4. Chronic tophaceous gout occurs when tophi (chalky deposits of sodium urate) invade the digital joints. The time from the first attack to tophi development averages 11.6 years. Effective treatment can prevent this debilitating stage; tophi damage is permanent.^1,4

The onset presentation of gout differs with age. Among younger individuals, gout affects predominantly males. Acute attacks are monoarticular in 85% to 90% of cases, generally affecting metatarsophalangeal joints. Tophaceous deposits generally occur around elbows and joints.⁸

Among the elderly, 50% to 60% of cases are women. After age 80, almost all new cases occur in women. More than 50% of attacks are polyarticular, and the upper extremities (distal and proximal interphalangeal joints) initially are affected. Tophaceous deposits appear earlier. Approximately 90% of women patients develop tophi, generally in the fingers, compared with only 8% of elderly men. Late-onset gout correlates strongly with frequent diuretic use and renal insufficiency.^8,9

Diagnosis

Misdiagnosis is common; the symptoms of gout can mimic joint infections and other arthritic conditions.³ A definitive diagnosis requires microscopic confirmation of monosodium urate crystals in synovial fluid. Samples may be taken after an acute attack, as some crystals remain indefinitely even in asymptomatic patients.²

Risk Factors

The stereotype of gout as a rich man's affliction results from its association with purine-rich foods such as meat and seafood. Purine-rich diets increase risk 1.41 times, compared with low-purine diets.¹⁰ Other risk factors include genetic predisposition (up to 18% of patients with gout have a family history of the disease); being overweight; environmental lead exposure; excessive alcohol intake (interfering with UA clearance); and drugs and biologics. Diuretics, salicylates, niacin, levodopa, nicotinic acid, cytotoxic drugs, vitamin B¹², and cyclosporine decrease UA clearance.^1,4,7,11

Treatment Considerations

Treatment goals are 3-fold: treat the acute attack, prevent recurrence, and lower UA levels. Treatment is not recommended for patients with simple hyperuricemia. Its causes, however, should be diagnosed and corrected.¹² Once gout is confirmed, treatment usually requires multiple medications.

Acute Attacks

Treatment should be initiated at the first sign of an attack. Available agents include nonsteroidal anti-inflammatory drugs (NSAIDs), corticotropin, colchicine, and corticosteroids. NSAIDS? especially indomethacin?are effective and often are prescribed for younger patients but are avoided in the elderly.⁸ Because of the potential dose-dependent toxicity of colchicine, its use generally is discouraged.⁷

Some practitioners recommend intraarticular corticosteroid treatment for elders because of its effectiveness and its lower-toxicity profile, compared with other options.⁸ Although cyclooxygenase- 2 inhibitors are used by some practitioners, few clinical trials exist demonstrating their effectiveness. The Table lists treatment options and side-effect profiles.

Drugs influencing serum urate levels?such as urate-lowering drugs, diuretics, cyclosporine, or salicylates?should not be introduced or withdrawn during an acute attack, because sudden changes in serum urate levels increase the duration of acute symptoms.¹² Cold packs and splints that minimize the joint's movement can offer some relief.

Prevention

Following an initial attack, patients' serum urate levels may normalize without antihyperuricemics, particularly if patients lose weight, switch to a nonthiazide agent, reduce or eliminate alcohol, and follow a purine-restricted diet. Many patients, however, have difficulty making lifestyle changes, and dietary modifications are only moderately effective.⁷

For recurrent attacks, the choice of an antihyperuricemic depends on the treatment objective: reducing urate production or increasing urate excretion. Because 75% of patients with primary gout have decreased urate excretion (rather than increased urate production), increasing urate excretion is prudent. Allopurinol is used most frequently because it reduces urate levels and decreases urate overproduction in almost all compliant patients.^7,8 Uricosuric drugs should be used with caution in the elderly.⁸

Treatment considerations regarding urate-lowering agents include the following:

• Allopurinol may cause pruritus, hepatic or renal damage, gastrointestinal (GI) effects, or severe hypersensitivity syndrome. Patients who are taking warfarin or who have renal impairment are poor candidates.
• The side effects of probenecid include headache, rash, and GI effects. It can modify the renal clearance of other drugs, and it is best used for patients with UA hyposecretion. Patients with urolithiasis or a creatinine clearance of <60 mL/min should avoid probenecid.
• Sulfinpyrazone inhibits platelet functioning, increases bleeding risk with warfarin, and may induce peptic ulcer and bone marrow depression. Urolithiasis and renal impairment are contraindications.^7-9

Conclusion

Gout is a disease that is easy to treat, but, if it is left untreated, progression is painful and debilitating. A good starting point for counseling may be to dispel the myth that gout is a middle-aged man's disease.

Dr. Zanni is a psychologist and health-systems consultant based in Alexandria,Va.Views expressed in this article are those of the author and not those of any government agency.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.