What are the implications of gout with normal uric acid levels?

From the Guidelines

Gout patients with normal uric acid levels should still be considered for urate-lowering therapy (ULT) if they experience recurrent attacks, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1.

Treatment Approach

For patients with gout and normal uric acid levels, the initial approach to managing an acute flare involves anti-inflammatory medications such as colchicine (0.6mg twice daily), naproxen (500mg twice daily), or prednisone (20-40mg daily with taper over 7-10 days) 1. Additionally, applying ice to the affected joint and resting it while elevated can help alleviate symptoms.

Urate-Lowering Therapy

Even with normal uric acid levels, long-term management may still require ULT, such as allopurinol, starting at a low dose (100mg daily) and titrating up as needed, to prevent future attacks 1. It's crucial to understand that serum uric acid levels represent a single point in time and may not reflect previous elevations that led to crystal deposition. Some patients may have localized supersaturation of urate in joint tissues despite normal serum levels.

Dietary Modifications

Dietary modifications to reduce purine intake and adequate hydration remain important preventive measures regardless of baseline uric acid levels. These lifestyle changes can help reduce the risk of future gout attacks.

Monitoring and Maintenance

For patients on ULT, serum uric acid (SUA) levels should be monitored and maintained at <6 mg/dL (360mmol/L) to prevent the formation of new urate crystals 1. In patients with severe gout, a lower SUA target (<5 mg/dL; 300mmol/L) may be recommended until total crystal dissolution and resolution of gout. However, SUA levels <3 mg/dL are not recommended in the long term due to potential adverse effects.

Key Considerations

• Allopurinol is recommended as first-line ULT, starting at a low dose and increasing as needed 1.
• Febuxostat or a uricosuric may be considered if allopurinol cannot be tolerated or if the SUA target cannot be reached with allopurinol alone 1.
• Prophylactic therapy with low-dose colchicine or low-dose NSAIDs may be used to reduce the risk of acute gout attacks in patients initiating ULT 1.

From the FDA Drug Label

An increase in acute attacks of gout has been reported during the early stages of administration of allopurinol tablets, even when normal or subnormal serum uric acid levels have been attained.

• Gout management: The use of colchicine or anti-inflammatory agents may be required to suppress gouty attacks in some cases.
• Dose adjustment: Patients with decreased renal function require lower doses of allopurinol tablets than those with normal renal function.
• Key consideration: Even with adequate therapy with allopurinol tablets, it may require several months to deplete the uric acid pool sufficiently to achieve control of the acute attacks. The patient with gout and normal serum uric acid levels may still experience acute attacks during the early stages of allopurinol administration 2.

From the Research

Gout with Normal Serum Uric Acid Levels

• Gout is typically characterized by elevated serum uric acid levels, but it can also occur with normal serum uric acid levels 3, 4.
• The diagnosis of gout is usually made using clinical criteria from the American College of Rheumatology, and may be confirmed by identification of monosodium urate crystals in synovial fluid of the affected joint 3, 5.
• Treatment of gout with normal serum uric acid levels is similar to treatment of gout with elevated serum uric acid levels, and includes nonsteroidal anti-inflammatory drugs, corticosteroids, or colchicine for acute attacks, and urate-lowering therapy for prevention of recurrent flares 3, 5, 6.
• Urate-lowering therapy, such as allopurinol or febuxostat, is typically used to reduce serum uric acid levels to <6 mg/dL, which is below the saturation point of monosodium urate crystals 4.
• It is essential to note that gout can be a progressive and debilitating disease if left untreated or improperly treated, and that treatment should be individualized based on patient-specific factors, such as comorbidities and medication use 5, 7.

Risk Factors for Gout with Normal Serum Uric Acid Levels

• Several risk factors have been identified for gout, including male sex, obesity, hypertension, alcohol intake, and diuretic use 5.
• Diet also plays a role in the development of gout, with a diet rich in meat and seafood, and high in fructose-rich foods and beverages, increasing the risk of gout 5, 6.
• Certain ethnic groups, such as Taiwanese, Pacific Islander, and New Zealand Maori, are also at increased risk of developing gout 5.

Management of Gout with Normal Serum Uric Acid Levels

• Management of gout with normal serum uric acid levels involves a combination of lifestyle modifications, such as dietary changes and avoidance of triggers, and pharmacologic therapy 3, 6.
• Patients should be educated about their diagnosis and management of the disease, including the importance of adherence to treatment guidelines and regular monitoring of serum uric acid levels 4.
• With proper treatment and management, gout is a curable disease, and patients can experience significant improvement in symptoms and quality of life 4, 7.