Gout

A 48 year old male presents to his primary care physician with sudden onset severe pain in the great toe of the left foot for 24 hours. The pain is sharp and intense, preventing him from bearing weight and performing daily activities. He has a history of hypertension and takes losartan and hydrochlorothiazide. He drinks alcohol regularly. On examination, there is a swollen, erythematous, and tender first metatarsophalangeal joint. Laboratory studies show normal serum uric acid levels. Synovial fluid analysis shows needle-shaped, negatively birefringent crystals. X ray of the foot is normal. Diagnosis?

Diagnosis is Acute gouty arthritis.

1. Definition

Gout is an acute inflammatory arthritis caused by deposition of monosodium urate crystals in joints, most commonly affecting the first metatarsophalangeal joint (podagra).

2. Epidemiology and Risk Factors

1. Male predominance
2. Peak incidence in the 4th to 6th decade
3. Risk factors include:
1. Hypertension
2. Obesity
3. Alcohol use
4. Chronic kidney disease
5. Thiazide diuretics
6. Metabolic syndrome

Hydrochlorothiazide increases uric acid levels, whereas losartan has a mild uricosuric effect.

3. Pathophysiology

1. Hyperuricemia leads to supersaturation of urate
2. Deposition of monosodium urate crystals in joints
3. Activation of neutrophil-mediated inflammation
4. Results in acute painful monoarthritis

4. Causes

4.1 Underexcretion (most common, ~90%)

1. Renal impairment
2. Thiazide and loop diuretics
3. Low dose aspirin
4. Lactic acidosis or ketoacidosis

4.2 Overproduction (~10%)

1. High cell turnover
• Malignancy, chemotherapy, psoriasis
2. Genetic enzyme defects
• Lesch Nyhan syndrome
• Von Gierke disease
3. Alcohol use

5. Clinical Features

1. Acute monoarthritis, classically involving the first MTP joint
2. Severe pain, swelling, erythema, and warmth
3. Joint is extremely tender to touch
4. Often occurs at night or early morning
5. May be triggered by alcohol, heavy meals, illness, or medications

6. Diagnosis

1. Synovial fluid analysis (gold standard)
• Needle-shaped, negatively birefringent monosodium urate crystals
2. Serum uric acid
• May be normal during acute attack
3. Laboratory findings
• Leukocytosis
• Elevated ESR and CRP
4. Imaging
• Early: normal
• Late: punched-out erosions with overhanging edges

7. Acute Management

1. NSAIDs
• Indomethacin, naproxen
• Avoid aspirin
2. Colchicine
• Effective if given early
• Side effects: diarrhea, nausea
3. Corticosteroids
• Oral or intra-articular if NSAIDs or colchicine are contraindicated

8. Chronic Management

Indicated for recurrent attacks, tophi, or complications

1. Lifestyle modification
• Reduce alcohol intake
• Avoid purine-rich foods
• Weight loss
2. Urate-lowering therapy
• Allopurinol (first line)
• Febuxostat as alternative
• Target serum urate <6 mg/dL
3. Uricosuric agents
• Probenecid
4. Uricase therapy
• Pegloticase for refractory disease
5. Prophylaxis during initiation of urate-lowering therapy
• Low-dose colchicine or NSAIDs

Urate-lowering therapy can be initiated during an acute flare if appropriate anti-inflammatory treatment is provided.

9. Key Clinical Insight

Acute monoarthritis of the first MTP joint with needle-shaped negatively birefringent crystals confirms gout, even if serum uric acid is normal

10. Exam Level Pearls

1. Podagra is the classic presentation of gout
2. Serum uric acid may be normal during an acute attack
3. Thiazide diuretics increase risk of gout
4. Needle-shaped, negatively birefringent crystals are diagnostic
5. Treat-to-target goal is serum urate <6 mg/dL