Gout is a metabolic inflammatory arthritis caused by deposition of monosodium urate (MSU) crystals in joints and peri-articular tissues due to persistent hyperuricemia. It is characterized by recurrent episodes of acute, intensely painful arthritis and may progress to chronic tophaceous gout with joint destruction if untreated.

Gout results from supersaturation of body fluids with uric acid, leading to crystal precipitation in joints, tendons, bursae, and soft tissues.

It is one of the most common forms of inflammatory arthritis worldwide and is more common in men than women (except post-menopausal women).

Pathophysiology

1. Hyperuricemia (serum urate >6.8 mg/dL)

2. Supersaturation → monosodium urate crystal formation

3. Crystal deposition in joints

4. Phagocytosis by neutrophils

5. Activation of NLRP3 inflammasome

6. Release of IL-1β and inflammatory cytokines

7. Acute intense inflammation

Chronic deposition leads to:

• Tophus formation

• Cartilage destruction

• Bone erosion

Causes of Hyperuricemia

1. Overproduction of Uric Acid

• High purine diet

• Alcohol excess

• Hematologic malignancy

• Tumor lysis syndrome

• Genetic enzyme defects

2. Underexcretion (Most Common)

• Chronic kidney disease

• Diuretics (thiazides, loop diuretics)

• Dehydration

• Lead nephropathy

3. Associated Conditions

• Obesity

• Hypertension

• Metabolic syndrome

• Diabetes mellitus

• Dyslipidemia

Stages of Gout

1. Asymptomatic hyperuricemia

2. Acute gouty arthritis

3. Intercritical period

4. Chronic tophaceous gout

Signs and Symptoms

Acute Gout Attack

• Sudden onset (often nocturnal)

• Severe, throbbing, crushing, or excruciating pain

• Swelling

• Redness

• Warmth

• Extreme tenderness (even bedsheet contact painful)

Commonly affected joints:

• First metatarsophalangeal joint (podagra)

• Ankle

• Knee

• Midfoot

• Elbow

• Wrist

Systemic symptoms may include:

• Low-grade fever

• Malaise

• Leukocytosis

Chronic Gout

• Persistent joint pain

• Joint deformity

• Tophus formation (chalky nodules on ears, fingers, elbows)

• Reduced joint mobility

Diagnostic Criteria

Diagnosis is confirmed by identification of MSU crystals.

Clinical Features

• Acute monoarthritis

• Nocturnal onset

• Severe pain

• Rapid peak within 24 hours

• Erythematous hot joint

• Recurrent episodes

Definitive Diagnosis

• Joint aspiration showing negatively birefringent needle-shaped crystals under polarized microscopy

Investigations

1. Serum Uric Acid

• Often elevated (>6.8 mg/dL)

• May be normal during acute attack

2. Synovial Fluid Analysis (Gold Standard)

• MSU crystals

• WBC elevated

3. Imaging

• X-ray (late disease): punched-out erosions

• Ultrasound: double contour sign

• Dual-energy CT: urate deposits

4. Renal Function Tests

• Assess kidney involvement

Differential Diagnosis

• Septic arthritis

• Pseudogout (calcium pyrophosphate deposition)

• Rheumatoid arthritis

• Reactive arthritis

• Osteoarthritis flare

Treatment

Management includes:

1. Treatment of acute attack

2. Prevention of recurrence

3. Long-term urate-lowering therapy

Pharmacological Treatment

A. Acute Attack

NSAIDs (First-line)

Ibuprofen

• 400 mg PO start, then 200 mg every 8 hours

• Continue until 24 hours after pain relief

Meloxicam

• 7.5–15 mg PO once daily for 5 days

Piroxicam

• 10–20 mg PO once daily for 5 days

Avoid NSAIDs in renal impairment, peptic ulcer, elderly high-risk patients.

B. Colchicine (Alternative)

• 1.2 mg initially, then 0.6 mg after 1 hour

• Low-dose preferred to reduce GI toxicity

C. Corticosteroids (If NSAIDs contraindicated)

• Prednisolone 30–40 mg daily for 5–10 daysOR

• Intra-articular steroid injection

Urate-Lowering Therapy (ULT)

Indications:

• ≥2 attacks per year

• Tophaceous gout

• Chronic kidney disease

• Urolithiasis

• Joint damage

Allopurinol

• Start 100 mg daily

• Gradually titrate

• Maximum up to 600 mg daily

• Target serum uric acid <6 mg/dL (preferably <5 mg/dL in severe disease)

Start after acute attack subsides (or with prophylaxis)

Febuxostat (Alternative)

• 40–80 mg daily

Treatment Targets

• Maintain serum uric acid:

  • <6 mg/dL (standard)

  • <5 mg/dL (tophaceous gout)

(Note: Modern guidelines recommend lower targets than 8 mg/dL.)

Non-Pharmacological Management

• Weight reduction in obese patients

• Avoid alcohol (especially beer and spirits)

• Reduce red meat and seafood

• Increase low-fat dairy intake

• Hydration (2–3 liters/day)

• Avoid sugary drinks

• Control hypertension and diabetes

Prevention

• Maintain uric acid at target level

• Continue urate-lowering therapy lifelong

• Avoid triggers

• Monitor renal function

• Regular follow-up

Complications

• Chronic joint destruction

• Tophus ulceration

• Renal stones

• Chronic kidney disease

• Cardiovascular disease risk

Prognosis

With proper treatment:

• Excellent prognosis

• Preventable joint damage

• Flares significantly reduced

Without treatment:

• Progressive joint deformity

• Disability

• Renal complications

Patient Education

• Gout is controllable

• Do not stop allopurinol during flares

• Adherence is essential

• Lifestyle modification is critical

• Report recurrent attacks