Gout — Crystal Identification and Urate-Lowering Therapy

Crystal identification and differential diagnosis

MSU crystal analysis of synovial fluid remains the gold standard for gout diagnosis, demonstrating needle-shaped crystals with negative birefringence under compensated polarised light microscopy. Calcium pyrophosphate (CPP) crystals, which cause pseudogout, show weakly positive birefringence and are rhomboid in shape. Both conditions may coexist (dual crystal disease). In the absence of synovial fluid analysis, the 2015 ACR/EULAR gout classification criteria use a scoring system incorporating clinical, laboratory, and imaging features including ultrasound double contour sign and dual-energy CT (DECT) for urate deposition.

• MSU crystals: needle-shaped, negatively birefringent (yellow when parallel to polariser axis)
• CPP crystals: rhomboid, weakly positively birefringence (blue when parallel)
• Ultrasound double contour sign: hyperechoic line over articular cartilage surface (urate deposition)
• DECT: colour-coded urate maps can identify MSU deposits without aspiration
• Commonly affected joints: first MTP (podagra), midfoot, ankle, knee, wrist
• Serum urate alone is insufficient for diagnosis; elevated urate may be absent during acute flares

Acute flare management

Acute gout flares should be treated within 24 hours for optimal efficacy. First-line options include colchicine (1.2 mg at onset followed by 0.6 mg one hour later, then 0.6 mg daily or twice daily until resolution), oral NSAIDs (indomethacin, naproxen, or celecoxib at maximum dose), or intra-articular corticosteroids for monoarthritis. For patients who cannot tolerate these agents or have polyarticular flares, intramuscular or intravenous corticosteroids (prednisolone 30-40 mg oral or methylprednisolone 120 mg IM) are effective. Prophylaxis against ULT-induced flares is mandatory: low-dose colchicine 0.6 mg once or twice daily for at least 3 to 6 months.

• Colchicine: 1.2 mg stat, 0.6 mg at 1 hour, then 0.6 mg BD; avoid in severe renal impairment
• NSAIDs: maximum dose for 5-7 days; avoid in renal impairment, heart failure, GI bleeding risk
• Intra-articular triamcinolone: ideal for monoarthritis (knee, ankle, wrist); rapid onset
• Oral prednisolone: 30-40 mg/day for 5-7 days then taper; effective for polyarticular flares
• Prophylaxis: colchicine 0.6 mg once or twice daily for >=3-6 months during ULT initiation
• Ice therapy: adjunctive; 20 minutes on, 20 minutes off; reduces pain and inflammation locally

Guidelines referenced:

• 2015 ACR/EULAR gout classification criteria
• EULAR 2016 updated recommendations for gout management
• ACR 2020 guideline for management of gout (including ULT initiation and titration)

Urate-lowering therapy: treat-to-target strategy

ULT is indicated for patients with >=2 flares per year, tophi, radiographic damage, or urate nephrolithiasis. Allopurinol is first-line, started at 100 mg daily (50 mg in CKD stage 3+) and titrated by 100 mg increments every 2 to 4 weeks targeting serum urate less than 6 mg/dL (or less than 5 mg/dL if tophi present). The HLA-B*58:01 allele testing is recommended before allopurinol initiation in Southeast Asian and African-American populations due to increased risk of severe hypersensitivity reactions (SJS/TEN). Febuxostat is an alternative xanthine oxidase inhibitor for allopurinol-intolerant patients.

• Allopurinol: start 100 mg/day, titrate by 100 mg every 2-4 weeks; max 800 mg/day if needed
• Target serum urate: <6 mg/dL (360 micromol/L); <5 mg/dL if tophi or severe disease
• HLA-B*58:01 testing mandatory before allopurinol in SE Asian, African-American, Korean populations
• Febuxostat: 40-80 mg/day; avoid in patients with cardiovascular disease (CARES trial concerns)
• Probenecid: uricosuric agent; contraindicated in nephrolithiasis or CKD stage 3+
• Pegloticase: IV pegylated uricase for refractory gout with tophi; requires pre-medication