Gout is the most common form of inflammatory crystal arthritis and results from the deposition of monosodium urate (MSU) crystals within joints, bursae, tendons, and surrounding soft tissues due to persistent hyperuricaemia. It is characterized by recurrent episodes of acute, intensely painful arthritis that may progress to chronic gouty arthritis, tophi formation, joint destruction, nephrolithiasis, and chronic kidney disease if left untreated.

Hyperuricaemia develops when serum uric acid concentrations exceed the saturation threshold, allowing MSU crystals to precipitate in tissues. However, not all individuals with hyperuricaemia develop gout. Management focuses on treating acute attacks, lowering serum urate levels, preventing recurrent flares, and reducing long-term complications.

Epidemiology

• Most common inflammatory arthritis in adults.

• More common in men than women.

• Incidence increases with age.

• Postmenopausal women have an increased risk.

• Strong association with obesity, hypertension, chronic kidney disease, diabetes mellitus, and metabolic syndrome.

Etiology

Hyperuricaemia results from either increased uric acid production, decreased renal excretion, or both.

Primary gout

Usually caused by inherited defects in renal urate handling leading to reduced uric acid excretion.

Secondary gout

May result from:

• Chronic kidney disease

• Myeloproliferative disorders

• Tumour lysis syndrome

• Psoriasis

• Haemolytic disorders

• Certain medications (e.g., thiazide and loop diuretics, low-dose aspirin, cyclosporine)

• Excessive alcohol consumption

• High-purine diet

Pathophysiology

Gout develops when serum uric acid concentrations exceed the physiological saturation point, resulting in the formation and deposition of monosodium urate crystals within joints and periarticular tissues. These crystals are recognised by macrophages, activating the NLRP3 inflammasome and triggering release of inflammatory cytokines, particularly interleukin-1β (IL-1β). This leads to rapid recruitment of neutrophils into the joint, producing the characteristic acute inflammatory response marked by severe pain, swelling, erythema, and warmth.

Repeated crystal deposition causes chronic synovial inflammation, progressive cartilage destruction, bone erosions, and formation of tophi, which are collections of urate crystals surrounded by chronic inflammatory cells. Persistent hyperuricaemia also increases the risk of uric acid nephrolithiasis and chronic urate nephropathy.

Risk factors

• Male sex

• Increasing age

• Family history

• Obesity

• Hypertension

• Chronic kidney disease

• Metabolic syndrome

• Diabetes mellitus

• Excess alcohol intake

• High-purine diet

• Sugar-sweetened beverages

• Diuretic therapy

• Low-dose aspirin

• Organ transplantation

Clinical presentation

Acute gout

Acute gout typically presents as a sudden onset monoarthritis, often occurring at night.

Features include:

• Excruciating joint pain

• Rapid onset over several hours

• Swollen joint

• Warmth

• Marked erythema

• Severe tenderness

• Restricted movement

• Difficulty bearing weight

• Low-grade fever in some patients

The first metatarsophalangeal (MTP) joint (podagra) is the most commonly affected site.

Other commonly involved joints include:

• Midfoot

• Ankle

• Knee

• Wrist

• Elbow

• Fingers

Intercritical gout

The asymptomatic period between acute attacks during which patients have no clinical manifestations despite persistent hyperuricaemia.

Chronic tophaceous gout

Develops after years of uncontrolled hyperuricaemia.

Features include:

• Chronic joint pain

• Persistent synovitis

• Tophi over fingers, elbows, Achilles tendon, ears, and toes

• Joint deformity

• Reduced joint mobility

• Bone erosions

• Recurrent attacks

Diagnostic criteria

According to current international recommendations, gout is diagnosed by demonstrating monosodium urate crystals or by a combination of characteristic clinical, laboratory, and imaging findings.

Diagnosis is supported by:

• Typical acute monoarthritis, particularly involving the first MTP joint

• Sudden onset of severe pain reaching maximal intensity within 24 hours

• Recurrent self-limiting attacks

• Hyperuricaemia (although serum uric acid may be normal during an acute flare)

• Identification of monosodium urate crystals in synovial fluid or tophus aspirate (gold standard)

• Imaging demonstrating urate deposition or characteristic erosions

Investigations

Laboratory investigations

• Serum uric acid level

• Complete blood count (CBC)

• Erythrocyte sedimentation rate (ESR)

• C-reactive protein (CRP)

• Renal function tests

• Liver function tests (before long-term urate-lowering therapy)

• Fasting blood glucose

• Lipid profile

Synovial fluid analysis (gold standard)

Findings include:

• Needle-shaped monosodium urate crystals

• Strong negative birefringence under polarized light microscopy

• Elevated white blood cell count with neutrophil predominance

• Gram stain and culture to exclude septic arthritis

Imaging

Plain X-ray

Usually normal in early disease.

Late findings include:

• Juxta-articular erosions

• "Overhanging edge" erosions

• Soft tissue tophi

• Preservation of joint space until late disease

Ultrasound

May demonstrate:

• Double-contour sign

• Tophi

• Synovitis

• Joint effusion

Dual-energy CT (DECT)

Can identify urate crystal deposits and is useful in diagnostically challenging cases where available.

Differential diagnosis

• Septic arthritis

• Calcium pyrophosphate deposition disease (pseudogout)

• Rheumatoid arthritis

• Reactive arthritis

• Psoriatic arthritis

• Cellulitis

• Osteoarthritis with acute synovitis

Management

Treatment aims to:

• Relieve acute pain

• Suppress inflammation

• Prevent recurrent attacks

• Lower serum urate concentration

• Prevent tophi and joint destruction

• Reduce renal complications

Non-pharmacological management

• Weight reduction in overweight or obese patients.

• Avoid alcohol, particularly beer and spirits.

• Reduce intake of purine-rich foods such as red meat, organ meats, shellfish, and certain fish.

• Avoid sugar-sweetened beverages and excessive fructose intake.

• Encourage regular exercise.

• Treat associated hypertension, diabetes, obesity, and chronic kidney disease.

• Maintain adequate hydration.

• Review medications that may increase uric acid levels where clinically appropriate.

Pharmacological treatment

Acute gout

Ibuprofen

• 400 mg orally immediately, then 200 mg orally every 8 hours until 24 hours after pain relief, usually for 3–5 days.

OR

Piroxicam

• 10–20 mg orally once daily for 5 days.

OR

Prednisolone

• 40 mg orally once daily for 3 days, followed by gradual tapering over 2–4 weeks.

• Administer together with an NSAID and a proton pump inhibitor according to the current STG.

OR

Methylprednisolone injection

OR

Triamcinolone injection

OR

Betamethasone injection

• For monoarticular flares:

  • Two vials for a large joint.

  • One vial for a small joint.

• Repeat every 2–12 weeks if necessary.

• Maximum of four injections per year for up to two years.

Urate-lowering therapy (chronic gout)

Urate-lowering therapy should generally be initiated after the acute flare has resolved unless there is a compelling indication to start earlier under specialist supervision.

First-line therapy

Allopurinol

• 100 mg orally once daily.

• Increase dose every 2–5 weeks according to serum uric acid concentration.

• Maximum dose: 600 mg/day.

• Continue treatment for at least 6 months.

Treatment target:

• Serum uric acid ≤6 mg/dL (≤360 μmol/L).

Second-line therapy

Febuxostat

• 10 mg orally once daily for 4 weeks.

• Then 20 mg orally once daily for 4 weeks.

• Then 40 mg orally once daily.

• Dose may be increased until serum uric acid reaches 6 mg/dL or lower.

• Continue treatment for at least 6 months.

Important treatment notes

• Monitor serum uric acid regularly and adjust therapy to achieve target levels.

• Continue urate-lowering therapy during future acute attacks unless contraindicated.

• Assess renal function before and during allopurinol therapy.

• Patients commencing long-term NSAIDs should receive gastroprotection with a proton pump inhibitor where appropriate.

• Evaluate and manage cardiovascular and renal comorbidities.

Nutritional management

The goal of nutritional therapy is to reduce uric acid production and promote uric acid excretion.

Recommendations include:

• Consume a low-purine diet by limiting red meat, organ meats, certain fish, alcohol, and other high-purine foods.

• Increase intake of fruits, vegetables, low-fat dairy products, tomatoes, green beans, citrus fruits, and other alkalinizing foods.

• Drink approximately 3 litres of fluid daily, adjusted according to clinical status, to promote uric acid excretion.

• Maintain moderate protein intake (approximately 0.8 g/kg/day).

• Ensure adequate carbohydrate intake to prevent ketosis.

• Limit dietary fat intake.

• Avoid large meals, particularly late in the evening.

• Encourage consumption of whole grains.

• Reduce intake of sugar-sweetened beverages and foods rich in fructose.

Monitoring and follow-up

Patients should be monitored for:

• Frequency of gout attacks

• Serum uric acid concentration

• Renal function

• Liver function (during febuxostat therapy)

• Development or resolution of tophi

• Adherence to lifestyle modification

• Adverse effects of medications

Complications

• Chronic gouty arthritis

• Tophi

• Joint destruction

• Chronic pain

• Joint deformity

• Uric acid nephrolithiasis

• Chronic kidney disease

• Reduced quality of life

Prognosis

The prognosis is excellent when hyperuricaemia is effectively controlled. Early initiation of urate-lowering therapy, maintenance of serum uric acid below the treatment target, adherence to lifestyle modification, and management of associated comorbidities substantially reduce recurrent attacks, prevent tophus formation, preserve joint function, and minimize long-term renal and musculoskeletal complications. Untreated or poorly controlled gout may progress to chronic destructive arthritis and permanent disability.