Gout

Definition

Gout is a metabolic disorder characterized by deposition of monosodium urate crystals in joints and periarticular tissues due to persistent hyperuricemia. It manifests clinically as recurrent attacks of acute inflammatory arthritis, chronic tophaceous deposits, and, in advanced stages, joint destruction.

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Etiology

Primary gout – due to inherited defects in purine metabolism or uric acid excretion
Secondary gout – associated with identifiable causes such as:

• Chronic kidney disease

• Myeloproliferative or lymphoproliferative disorders

• Medications (e.g., thiazide diuretics, loop diuretics, low-dose aspirin, cyclosporine, tacrolimus, pyrazinamide, ethambutol)

• High purine diet and alcohol excess

• Lead intoxication

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Pathophysiology

• Hyperuricemia: Serum uric acid > 6.8 mg/dL (404 μmol/L) exceeds solubility threshold, leading to precipitation of monosodium urate crystals in cooler peripheral joints.

• Crystals activate NLRP3 inflammasome in macrophages, triggering interleukin-1β release, neutrophil recruitment, and intense inflammatory response.

• Over time, chronic inflammation leads to tophi (aggregates of urate crystals surrounded by granulomatous inflammation).

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Risk Factors

• Male sex (4:1 male-to-female ratio before menopause)

• Middle to older age

• Family history of gout

• Obesity, metabolic syndrome, hypertension, chronic kidney disease

• Diet high in purine-rich foods (red meat, seafood) and fructose-sweetened beverages

• Alcohol intake (especially beer and spirits)

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Clinical Features

1. Acute gout attack

• Sudden onset, often at night or early morning

• Severe joint pain, swelling, warmth, erythema

• Most commonly affects the first metatarsophalangeal joint (podagra)

• Other joints: ankle, knee, midfoot, wrist, elbow

• Fever may occur in severe attacks

2. Intercritical gout

• Asymptomatic interval between attacks, progressively shorter without treatment

3. Chronic tophaceous gout

• Firm nodules (tophi) over joints, cartilage, tendons, ear helix

• May ulcerate and discharge chalky material

• Associated with chronic joint damage and deformity

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Diagnosis

Clinical diagnosis is supported by:

• Typical acute monoarthritis with rapid onset

• History of hyperuricemia

• Response to colchicine or NSAIDs

Definitive diagnosis:

• Synovial fluid analysis – negatively birefringent needle-shaped monosodium urate crystals under polarized light microscopy

• Serum uric acid: Often elevated, but may be normal during acute attack

• Imaging:

  • X-ray: Joint space preservation early, punched-out erosions with overhanging edges in chronic gout

  • Ultrasound: Double contour sign (urate deposition on cartilage surface)

  • DECT (dual-energy CT): Detects urate crystal deposits

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Differential Diagnosis

• Septic arthritis

• Calcium pyrophosphate deposition disease (pseudogout)

• Reactive arthritis

• Psoriatic arthritis

• Rheumatoid arthritis

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Management

Goals:

• Relieve acute attack

• Prevent recurrent attacks

• Reduce serum uric acid and dissolve urate deposits

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1. Management of Acute Gout Attack

First-line agents (start as soon as possible):

• NSAIDs: e.g., Indomethacin 50 mg orally three times daily for 2–3 days, then taper; or Naproxen 750 mg once, then 250 mg every 8 hours until resolution; avoid in renal impairment or peptic ulcer disease

• Colchicine: 1.2 mg orally at onset, followed by 0.6 mg one hour later (max 1.8 mg in 24 hours); dose reduce in renal or hepatic impairment

• Corticosteroids:

  • Oral Prednisolone 30–40 mg daily for 5 days, then stop or taper

  • Intra-articular Triamcinolone or Methylprednisolone for monoarticular attacks when infection is excluded

Adjunct: Rest, elevation, ice packs to affected joint

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2. Prophylaxis Against Recurrence (During Urate-lowering Initiation)

• Low-dose Colchicine 0.5–0.6 mg once or twice daily

• Low-dose NSAIDs (e.g., Naproxen 250 mg twice daily) if tolerated

• Continue for at least 3–6 months after urate target is achieved

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3. Long-term Urate-lowering Therapy (ULT)

Indications:

• ≥2 attacks per year

• Tophaceous gout

• Chronic kidney disease stage 2 or worse

• Uric acid nephrolithiasis

Target serum uric acid: <6 mg/dL (360 μmol/L), <5 mg/dL (300 μmol/L) in severe disease

First-line:

• Allopurinol: Start at 100 mg/day orally, titrate every 2–5 weeks up to 300–900 mg/day; adjust in renal impairment; risk of hypersensitivity syndrome

• Febuxostat: 40–80 mg/day orally; alternative for allopurinol intolerance; caution in cardiovascular disease

Uricosuric agents (increase renal uric acid excretion):

• Probenecid 250 mg twice daily → increase to 500–1000 mg twice daily; avoid in nephrolithiasis or severe CKD

Refractory cases:

• Pegloticase (IV recombinant uricase) 8 mg every 2 weeks – for severe, refractory tophaceous gout

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4. Lifestyle and Dietary Modification

• Increase water intake (≥2 liters/day)

• Limit red meat, organ meats, shellfish

• Reduce fructose-containing soft drinks

• Avoid excess alcohol (beer, spirits)

• Maintain healthy weight and regular exercise

• Limit high-purine vegetables (spinach, asparagus, mushrooms – less impact than meats)

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Prognosis

• Excellent with early diagnosis and appropriate management

• Without treatment, attacks become more frequent and severe, leading to chronic arthritis and tophi

• Proper ULT can dissolve urate deposits and prevent joint damage