Gout

Potentially disabling and erosive inflammatory arthritis caused by the deposition of monosodium urate crystals into joints and soft tissues

Aetiology

• Usually due to high serum uric acid levels (hyperuricaemia)

Causes of hyperuricaemia

• High dietary purine intake (red meat, seafood, corn syrup)

• Alcohol

• Inherited enzyme defects
• Usually idiopathic - 90% unknown enzyme deficiency
• HGPRT enzyme deficiency impaires purine nucleotide salvage pathway → degraded to urate

• Myeloproliferative/lymphoproliferative disorders

• Psoriasis

• Haemolytic disorders

• Chronic renal impairement

• Volume depletion e.g. heart failure

• Hypothyroidism

• Diuretics

• Cytotoxics e.g. cyclosporin

Risk factors

• Age - rare under 20, decreases after age 80

• More common in men than women

• Very rare in women before the menopause (oestrogen is protective)

• Some evidence for a genetic predisposition

Pathophysiology

• ↑ Serum uric acid (≥ 6.8 mg/dL) → supersaturation → urate crystal formation.

• Crystals deposit in joints (commonly big toe/MTP I).

• Phagocytosis by neutrophils → inflammatory response:
• Activation of NLRP3 inflammasome
• ↑ IL-1β, prostaglandins, TNF-α
→ intense acute joint inflammation.

• Overproduction (10% cases): high purine metabolism, hemolysis, tumor lysis syndrome.

• Underexcretion (90% cases): renal impairment, dehydration, drugs (thiazide, loop diuretics), alcohol.

Clinical presentation

Acute Gout Attack

• Sudden severe joint pain, often monoarticular.

• Common site: first metatarsophalangeal joint (podagra).

• Signs:
• Red, hot, swollen joint.
• Extreme tenderness (pain even with light contact).
• Fever may accompany severe attacks.

• Typically peaks within 24 hours.

• Resolves within 3–14 days.

Intercritical Period

• Asymptomatic intervals between attacks.

• Duration varies (weeks–years).

Chronic Tophaceous Gout

• Occurs after years of recurrent attacks.

• Tophi: firm urate deposits in:
• fingers, toes, helix of ear, olecranon.

• Chronic polyarticular pain, joint destruction, deformity.

Investigations

Bloods

• Serum uric acid raised (≥ 6.8 mg/dL)
• May be normal during acute attack (~40%)

• Raised inflammatory markers

• Renal function (ACR and GFR) - cause or effect

Aspiration of synovial fluid — Gold Standard

• Polarised microscopy - needle shaped, negative birefringent crystals

• Gram stain and culture to rule out septic arthritis in acute gout

X-rays

• Erosion may be visible in long-standing gout

Management

Acute Attack Management

1. NSAIDs (first line) — Indomethacin 50 mg 3x1
• Start 24-48 hr after attack

2. Colchicine — start 1 mg/day, then 0.5 mg/day
• Best if started early <12 hr after attack; reduces neutrophil activity.

3. Corticosteroids
• Oral/IA injection if NSAIDs/colchicine intolerant — prednisone 0.5 mg/kg

4. Rest, elevate joint, ice compress.

Long-Term Management (Urate-Lowering Therapy—ULT)

• Serum uric acid ≥ 9 mg/dL and asymptomatic

• Recurrent attacks ≥2/year.

• Tophaceous gout.

• CKD stage ≥3.

• History of renal stones.

• Xanthine oxidase inhibitors:
• Allopurinol (first line) — 100 mg/day, max 800 mg/day
• Febuxostat (if intolerant)

• Uricosurics:
• Probenecid 1-2 gram/day

• Recombinant uricase:
• Pegloticase (severe refractory cases).

• Low-dose colchicine 0.5-1 mg/day for 6 months to prevent flare.

Lifestyle Modification

• Reduce purine-rich foods.

• Limit alcohol & sugary beverages.

• Increase water intake.

• Weight reduction, exercise.

• Avoid precipitating drugs if possible.

Serum Uric Acid Target

• <6 mg/dL

• Severe gout (tophus, recurrent gout attack, chronic arthropathy) → <5 mg/dL