Key Facts

Gout results from chronic hyperuricaemia leading to MSU crystal deposition in and around joints. It is an increasingly prevalent condition strongly associated with metabolic syndrome. Primary care management focuses on acute attack treatment and long-term urate reduction to prevent recurrence and joint damage.

Epidemiology

• Prevalence: 2.5% of UK adults (approximately 1.6 million people)
• Male:female ratio 4:1; rare in premenopausal women (oestrogen is uricosuric)
• Peak incidence: men aged 40-60; women usually postmenopausal
• Prevalence increasing due to rising obesity, metabolic syndrome, and ageing population

Aetiology

• Underexcretion of uric acid (90%): renal impairment, diuretics, low-dose aspirin, cyclosporine
• Overproduction of uric acid (10%): high purine diet (red meat, offal, shellfish, beer), myeloproliferative disorders, tumour lysis syndrome, Lesch-Nyhan syndrome
• Risk factors: obesity, metabolic syndrome, hypertension, diabetes, CKD, alcohol (especially beer and spirits), sugary drinks (fructose), family history
• Drugs that raise urate: thiazide and loop diuretics, low-dose aspirin, pyrazinamide, cyclosporine

Pathophysiology

• Chronic hyperuricaemia (serum urate >360 μmol/L) leads to MSU crystal formation and deposition in joints and soft tissues
• Crystal shedding into the joint space triggers acute inflammatory response via NLRP3 inflammasome activation, IL-1β release, and neutrophil recruitment
• Chronic crystal deposition leads to tophi formation and erosive arthropathy
• Not all hyperuricaemic individuals develop gout (only approximately 20-25% with urate >360 μmol/L develop clinical gout)

Acute Gout Attack

• Rapid onset (often overnight) of severe monoarthritis
• First MTP joint (podagra) in 50-70% of first attacks
• Other common sites: ankle, midfoot, knee, wrist, finger joints
• Exquisitely tender, red, hot, swollen joint
• May have fever and malaise
• Attack peaks at 12-24 hours, resolves over 7-14 days

Chronic Tophaceous Gout

• Tophi: firm, white/yellow nodules in skin, ears, tendons, joints
• Chronic joint pain and stiffness
• Joint deformity and erosion
• Develops after years of inadequately treated hyperuricaemia

Red Flags

• Hot, swollen joint with fever — must exclude septic arthritis (emergency joint aspiration)
• Polyarticular acute presentation — consider pseudogout, RA, or septic arthritis
• Young patient with gout — investigate for secondary causes (haematological malignancy, enzyme deficiency)
• Recurrent attacks without ULT — increasing risk of chronic tophaceous gout and renal stones

Bedside

• Examination of affected joint: red, hot, swollen, exquisitely tender
• Assess for tophi (ears, elbows, fingers, Achilles tendon)
• Temperature

Bloods

• Serum urate: >360 μmol/L supports diagnosis BUT may be normal during acute attack (up to 40%)
• FBC, CRP/ESR: raised inflammatory markers
• U&Es: assess renal function (CKD is both cause and effect)
• Lipid profile and HbA1c: metabolic syndrome screening

Joint Aspiration

• Gold standard for diagnosis: negatively birefringent needle-shaped MSU crystals under polarised light microscopy
• Also excludes septic arthritis (Gram stain, culture, WCC >50,000/mm³ suggests infection)

Imaging

• X-ray: normal in early disease; later shows punched-out erosions with overhanging edges, preserved joint space (cf. RA)
• Ultrasound: double contour sign (MSU crystal deposition on cartilage surface)
• Dual-energy CT: can identify urate crystal deposits; useful in diagnostic uncertainty

Special Tests

• 24-hour urinary urate: if overproduction suspected
• Urine pH and renal USS: if uric acid nephrolithiasis suspected

Non-pharmacological

• Lifestyle modification: weight loss, reduce alcohol (especially beer/spirits), reduce purine-rich foods, adequate hydration
• Rest and elevate affected joint during acute attack
• Ice pack application (20 minutes) for pain relief
• Review medications: consider switching thiazides to alternatives
• Patient education about chronic nature and importance of ULT adherence

Pharmacological

Acute attack (NICE NG219):

• First-line: naproxen 750mg stat then 250mg TDS until attack resolves (with PPI cover)
• Or: colchicine 500mcg BD-TDS (max 6mg per course; avoid if eGFR <10; reduce dose in renal impairment)
• Or: prednisolone 30-35mg OD for 5 days (if NSAIDs and colchicine contraindicated)
• Intra-articular corticosteroid: triamcinolone 10-40mg for single joint involvement
• Paracetamol as adjunctive analgesia
• Avoid aspirin during acute attack (alters urate levels)

Urate-lowering therapy (NICE NG219):

• Discuss ULT with all patients after first attack; offer after second attack or if tophi, CKD, urate renal stones, or diuretic use
• Allopurinol (xanthine oxidase inhibitor): first-line
  • Start 100mg OD (50mg if eGFR <20); titrate by 100mg every 4 weeks
  • Target serum urate <300 μmol/L (or <360 μmol/L)
  • Common side effects: rash (stop if severe — risk of allopurinol hypersensitivity syndrome)
  • HLA-B*5801 testing before starting in patients of Han Chinese, Thai, or Korean descent (high risk of severe hypersensitivity)
• Febuxostat 80-120mg OD: second-line if allopurinol not tolerated/contraindicated (NICE TA164; CARES trial: monitor cardiovascular risk)

Flare prophylaxis during ULT initiation:

• Colchicine 500mcg OD-BD for first 6 months of ULT
• Or low-dose NSAID with PPI cover for 6 months

Surgical

• Surgical removal of large/debilitating tophi (rarely needed)
• Joint replacement for severe erosive gout

Referral Criteria

• Diagnostic uncertainty: rheumatology referral
• Refractory gout despite adequate ULT: rheumatology (consider uricosurics, biologic therapy)
• Young-onset gout (<30 years) or suspected secondary cause: further investigation
• Severe allopurinol hypersensitivity reaction: urgent dermatology/immunology

• Acute gout: resolves within 7-14 days with treatment; untreated attacks typically self-limit within 1-2 weeks
• Recurrence: without ULT, 60% have a second attack within 1 year; 78% within 2 years
• Chronic tophaceous gout: develops in 20-30% if untreated over 5-10 years
• With adequate ULT (serum urate <300 μmol/L): tophi resolve, attack frequency reduces to zero in >80% within 2-5 years
• Associated comorbidities: gout independently associated with 2-fold increased CV risk, CKD, and metabolic syndrome
• Uric acid renal stones: occur in 10-20% of gout patients

Urate-Lowering Therapy Decision

Allopurinol Titration Protocol