Key Facts

Gout is the most common inflammatory arthritis in developed countries. It is curable with effective urate-lowering therapy, yet remains widely under-treated.

Epidemiology

• UK prevalence: ~3.2% (~2.5% men, ~1.4% women); increasing
• M:F 4:1 (pre-menopausal women rarely affected – oestrogen is uricosuric)
• Peak incidence: men 40-60 years; women post-menopausal
• Prevalence increasing due to obesity, metabolic syndrome, ageing, diuretic use

Aetiology

• Hyperuricaemia (serum urate >360 µmol/L) is the primary risk factor
• Under-excretion of urate (90%): CKD, diuretics (thiazide, loop), low-dose aspirin, ciclosporin
• Over-production of urate (10%): myeloproliferative disorders, tumour lysis syndrome, Lesch-Nyhan syndrome, high-purine diet
• Dietary risk factors: red meat, shellfish, alcohol (especially beer), fructose-sweetened drinks
• Protective factors: vitamin C, coffee, cherries (limited evidence)

Pathophysiology

• Hyperuricaemia → MSU crystal deposition in joints, tendons, soft tissues
• Crystals activate NLRP3 inflammasome → IL-1β release → intense neutrophilic inflammation
• Acute gout: phagocytosis of crystals by neutrophils → intense pain and swelling
• Chronic tophaceous gout: deposition of large urate collections in soft tissues and joints
• Crystals can be present in joints for years before first clinical attack

Acute Gout

• Sudden-onset excruciating monoarthritis (often nocturnal)
• 1st MTP (podagra) in 50-70% of first attacks
• Also: ankle, knee, wrist, elbow, small hand joints
• Joint is red, hot, swollen, exquisitely tender (cannot bear weight or touch)
• Overlying skin may peel during resolution
• Self-limiting: resolves in 7-14 days without treatment

Chronic Tophaceous Gout

• Tophi: chalky deposits of MSU crystals in skin, joints, cartilage
• Common sites: pinnae of ears, olecranon, Achilles tendon, fingers
• Joint destruction and deformity
• Chronic pain and disability

Associated Conditions

• Metabolic syndrome: obesity, hypertension, diabetes, dyslipidaemia
• CKD: both cause and consequence
• Renal stones: uric acid stones (10% of gout patients)
• Cardiovascular disease: increased CV risk

Red Flags

• Monoarthritis + fever → exclude septic arthritis (MUST aspirate)
• First attack in pre-menopausal woman → unusual; consider secondary causes
• Very high urate + renal impairment → consider tumour lysis syndrome

Gold Standard

• Joint aspiration: needle-shaped, negatively birefringent crystals under compensated polarised light microscopy
• Also: WCC elevated (typically 10,000-50,000/mm³; if >50,000 consider septic arthritis)
• Send for Gram stain and culture (exclude co-infection)

Bloods

• Serum urate: may be NORMAL during acute attack (urate drops during inflammation); repeat 2-4 weeks after attack
• FBC: leucocytosis
• CRP/ESR: elevated
• U&Es: assess renal function (CKD common)
• Lipid profile, HbA1c, LFTs: metabolic syndrome screening

Imaging

• X-ray: normal in early disease; chronic: well-defined "punched-out" erosions with overhanging margins ("rat-bite" erosions), soft tissue tophi
• Dual-energy CT (DECT): identifies MSU crystal deposits; useful for diagnosis in difficult cases
• Ultrasound: "double contour sign" (MSU crystal layer on cartilage surface); hyperechoic aggregates

Acute Gout (NICE CKS / BSR Guidelines)

First-line (choose one):

• NSAID: naproxen 750mg stat then 250mg TDS (with PPI) until attack resolves
• Colchicine: 500mcg BD-TDS until attack resolves (max 6mg per course); preferred if NSAID contraindicated
• Prednisolone: 30-40mg OD for 5 days; or IM depomedrone 120mg; preferred if NSAID and colchicine contraindicated

Adjuncts:

• Rest, ice, elevate affected joint
• Intra-articular corticosteroid if single large joint

NOT recommended acutely:

• Do NOT start or stop allopurinol during acute attack
• Avoid aspirin (alters urate handling)

Urate-Lowering Therapy (Chronic Management)

Indications:

• ≥2 attacks per year
• Tophi present
• Renal stones
• CKD
• Concurrent diuretic therapy
• Consider after first attack if high urate or severe presentation

First-line:

• Allopurinol: start 100mg OD (50mg if eGFR <20); titrate by 100mg every 4 weeks to target urate <360 µmol/L (or <300 if tophi)
• Max dose: 900mg (limited by tolerability; most need 300-600mg)
• Cover initiation with colchicine 500mcg OD for 6 months to prevent flares during urate lowering

Second-line:

• Febuxostat 80mg OD (titrate to 120mg): if allopurinol intolerant/ineffective (NICE TA164)
  • CARES trial: slightly increased CV mortality vs allopurinol; use with caution in established CVD
• Uricosuric: benzbromarone (unlicensed in UK), probenecid (rarely used)

Lifestyle:

• Weight loss, reduce alcohol (especially beer), reduce purine-rich foods, increase hydration, reduce fructose intake
• Review medications: switch thiazide to alternative if possible; losartan and fenofibrate have mild uricosuric effect

Referral Criteria

• Diagnostic uncertainty (especially if septic arthritis cannot be excluded) → rheumatology
• Tophaceous gout or refractory disease → rheumatology
• Severe gout with CKD → nephrology/rheumatology

• Acute attacks are self-limiting (7-14 days) but recurrence rate is high (60% within 1 year, 78% within 2 years) without ULT
• ULT can render patients symptom-free with complete tophus resolution over months-years
• Target urate maintenance <360 µmol/L prevents crystal formation and allows dissolution
• Cardiovascular risk: gout is an independent risk factor for MI and CVD mortality
• Renal stones: 10-20% of gout patients; uric acid stones can be dissolved with urinary alkalinisation
• Gout is curable with effective ULT – yet remains under-treated in >50% of patients

Gout vs Pseudogout

Drugs Affecting Urate Levels