Is it safe to continue allopurinol therapy during an acute gout attack, or does it risk worsening the flare?
Acute gout attacks are characterized by painful joint inflammation caused by immune cells attacking urate crystals. While chronic management to lower blood urate levels is crucial for preventing flare-ups, the approach to using urate-lowering therapies such as allopurinol during an acute gout attack continues to evolve. This blog will clarify some of the clinical considerations and evidence surrounding the use of allopurinol during acute gout episodes.
The Dilemma: Traditional Teaching vs. Emerging Evidence. Traditionally, initiating or adjusting allopurinol during an acute attack was discouraged, as altering uric acid levels can exacerbate symptoms. This concept led to a common recommendation of holding off allopurinol until the acute phase subsides. However, recent evidence has challenged this approach, suggesting that allopurinol, if already in use, should be continued during acute attacks to maintain steady uric acid levels and prevent rebound hyperuricaemia.
Mechanism of Action and Rationale. Allopurinol is a xanthine oxidase inhibitor that reduces uric acid production, thus lowering serum urate levels and preventing urate deposition in the joints and crystal formation. Sudden changes in serum urate can mobilize existing urate crystals out from the joints. As the crystals are mobilized, they may be more vulnerable to recognition and attack by immune cells. This can worsen symptoms, either worsening an ongoing acute attack or precipitating acute gout attacks. For this reason, initiating allopurinol or drastically changing its dose during an acute gouty attack was traditionally avoided. However, clinical guidelines have been shifting to encourage stable urate management, even during acute flares.
What Do Current Guidelines Say? The 2020 American College of Rheumatology (ACR) guidelines recommend continuing allopurinol during acute attacks if the patient is already on a stable dose. In 2023, the Singapore Agency for Care Effectiveness (ACE) released an updated ACE Clinical Guidance (ACG) on “Gout – achieving the management goal” advising concerning urate-lowering therapy (ULT) to consider starting with allopurinol and to “Continue ULT during an acute flare”. In 2024, the Singapore Health Science Authority (HSA) and ACE updated patient information on the safe usage of allopurinol, advising: “When you first start treatment with allopurinol, you may have more gout attacks as the drug starts to work. You should continue to take it every day even if this happens.” The rationale is that withholding or altering the dose may result in a surge in serum urate levels, which can prolong the attack or increase the risk of future flares. However, starting allopurinol for the first time during an acute flare is generally discouraged unless accompanied by appropriate anti-inflammatory coverage (e.g., colchicine, NSAIDs or corticosteroids). Even between acute gouty attacks, it is strongly recommended to accompany starting on allopurinol with adequate anti-inflammatory prophylaxis therapy to reduce the risk of precipitating acute flares.
Conclusion. While traditional guidance discouraged the use of allopurinol during acute gouty attacks, recent evidence and updated guidelines suggest that continuing the medication, if already prescribed, is beneficial. Initiating or changing doses, however, should be approached with caution and in conjunction with appropriate anti-inflammatory therapy. This example serves as a reminder that clinical guidelines evolve as knowledge advances. It is essential to continually stay up-to-date and tailor your approach to each patient’s unique clinical scenario.
References and further reading:
ACR 2020: https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.24180
HSA 2024: https://www.hsa.gov.sg/consumer-safety/articles/safe-use-of-allopurinol
HSA/ACE 2024: https://www.hsa.gov.sg/docs/default-source/announcements-csg/patient-fact-sheet.pdf?sfvrsn=7edd47d2_1
Gaffo AL, Dalbeth, N, Case SM (2024) Gout: Treatment of flares, UpToDate (https://www.uptodate.com/contents/gout-treatment-of-flares)
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