A patient with a history of gout and currently in remission is started on allopurinol. He develops a severe gouty attack in the first few weeks. This phenomenon is best explained by:
- A Allopurinol inhibits xanthine oxidase, causing xanthine accumulation which directly activates NLRP3 inflammasome
- B Allopurinol is an antigenic hapten that triggers immune-mediated crystal formation
- C The active metabolite oxypurinol precipitates in joints at physiological temperature
- D Allopurinol lowers serum urate, destabilizing existing joint urate crystal deposits and causing their mobilization ✓
Explanation
When urate-lowering therapy is initiated, falling serum urate levels cause partial dissolution of existing monosodium urate (MSU) crystal deposits in joint tissues and tophi. During this dissolution phase, microcrystals shed from the crystal matrix are engulfed by neutrophils and macrophages, triggering IL-1β-mediated inflammation via the NLRP3 inflammasome—precipitating a flare. Colchicine or low-dose NSAIDs given prophylactically for the first 3–6 months of allopurinol therapy prevent this mobilization flare. Allopurinol itself does not cause crystal deposition.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.