What is the optimal management for a patient with recurrent gout (gouty arthritis) flare-ups and normal serum uric acid levels, experiencing two episodes in less than a month?

From the Guidelines

For a patient with gout flare-ups despite normal uric acid levels who has experienced two flares in less than a month, I recommend treating the acute flare with anti-inflammatory medications while also considering long-term preventive therapy, as suggested by the 2020 American College of Rheumatology guideline for the management of gout 1.

Treatment of Acute Flare

For the acute flare, start with colchicine 1.2 mg followed by 0.6 mg one hour later, then 0.6 mg once or twice daily until the flare resolves, as this regimen has been shown to be effective in reducing pain in patients with acute gout 1. Alternatively, use NSAIDs such as naproxen 500 mg twice daily or indomethacin 50 mg three times daily for 7-10 days. For patients who cannot take these medications, a short course of prednisone 30-40 mg daily for 3-5 days with a taper over 10-14 days is appropriate.

Long-term Preventive Therapy

Despite normal serum uric acid levels, consider urate-lowering therapy such as allopurinol starting at 100 mg daily and gradually increasing to achieve a target uric acid level below 6 mg/dL, as normal serum levels don't rule out tissue urate crystal deposition 1.

• Advise lifestyle modifications including:
  • Weight loss if overweight
  • Limiting alcohol (especially beer)
  • Avoiding high-purine foods like organ meats and shellfish
  • Maintaining good hydration The frequent flares despite normal uric acid levels suggest that either the patient has intermittent hyperuricemia not captured by testing, or crystal deposition has already occurred in joints despite current normal levels. Initiation of urate-lowering therapy is strongly recommended for patients with frequent gout flares, as it can reduce the long-term risk of acute gout attacks 1.

From the FDA Drug Label

The recommended dosage of Colchicine Tablets, USP for prophylaxis of gout flares for adults and adolescents older than 16 years of age is 0.6 mg once or twice daily. An increase in gout flares may occur after initiation of uric acid-lowering therapy, including pegloticase, febuxostat and allopurinol, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Colchicine Tablets, USP are recommended upon initiation of gout flare prophylaxis with uric acid-lowering therapy Prophylactic therapy may be beneficial for at least the first six months of uric acid-lowering therapy. General 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. Accordingly, maintenance doses of colchicine generally should be given prophylactically when allopurinol tablets are begun

The patient should be treated with colchicine for prophylaxis of gout flares at a dose of 0.6 mg once or twice daily. Additionally, allopurinol may be initiated at a low dose of 100 mg daily and increased at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained, but without exceeding the maximum recommended dose. It is also recommended to maintain a fluid intake sufficient to yield a daily urinary output of at least 2 liters and to keep the urine neutral or slightly alkaline 2 3.

• Key points:
  • Colchicine for prophylaxis of gout flares
  • Allopurinol for uric acid lowering therapy
  • Maintain adequate fluid intake and urine pH
  • Monitor serum uric acid levels and adjust dosage as needed
  • Consider concomitant use of colchicine and allopurinol to prevent gout flares during initiation of uric acid-lowering therapy 2 3

From the Research

Treatment of Gout Flare Ups with Normal Uric Acid Levels

• For patients with gout flare ups and normal uric acid levels, the diagnosis of acute gout attack should not be excluded if the clinical manifestations or the positive response to colchicine are suggestive of gout 4.
• Standard pharmacotherapies for gout flares include colchicine, NSAIDs, and oral or intramuscular corticosteroids, with IL-1 inhibitors as an option for flare refractory to standard therapies 5, 6.

Prevention of Gout Flare Ups

• Urate-lowering therapies aim to prevent gout flares, with an emphasis on treat-to-target strategy; the escalation of therapies until the target serum uric acid is reached 5.
• Allopurinol and febuxostat are initial treatments for urate-lowering therapy, with uricosuric agents as adjuncts 5, 6.
• Low-dose colchicine (0.6 mg/day) can adequately prevent gout flare with fewer adverse events compared with regular-dose colchicine (1.2 mg/day) 7.

Considerations for Patients with Recurrent Gout Flare Ups

• For patients with recalcitrant gout, pegloticase is effective, but its immunogenicity significantly threatens the achievement of sustained urate lowering responses 6.
• The risk of gout flares is associated with serum uric acid levels, and higher levels are associated with an increased risk of gout flares in a dose-response manner 8.
• Patients with recurrent gout flare ups should be closely monitored and their treatment adjusted accordingly to prevent further flare ups 5, 6.