Gout Overview

Gout is an inflammatory arthritis characterized by episodic flares of intense joint pain and swelling caused by monosodium urate crystal deposition. It affects up to 4% of adults worldwide, with prevalence rising alongside increasing rates of obesity, hypertension, and metabolic syndrome.

Pathophysiology

• Uric acid metabolism: Uric acid is the end product of purine catabolism in humans (lack of uricase). It is generated in the liver and eliminated primarily by the kidneys (~70%) and gut (~30%).
• Hyperuricemia mechanisms:
  • Underexcretion: Impaired renal tubular secretion due to genetic predisposition, chronic kidney disease, diuretics, or salicylates. 90% of cases.
  • Overproduction: Excess purine turnover in high-purine diets, malignancies, hemolytic disorders, or metabolic enzyme defects (HGPRT deficiency). ~10% of cases.
  • Mixed causes: A combination of underexcretion and overproduction in some patients.

Clinical Presentation

• Acute gout flare: Sudden onset of severe pain, erythema, warmth, and swelling—classically affecting the first metatarsophalangeal joint (podagra), but can involve ankles, knees, wrists, elbows, and other joints. Peak intensity within 24 hours, resolving over 7–10 days if untreated.
• Intercritical period: Asymptomatic intervals during which subclinical crystal deposition continues.
• Chronic tophaceous gout: Persistent hyperuricemia leads to tophi—aggregates of crystals in soft tissues and joints—causing chronic pain, deformity, and risk of erosive damage.

Diagnosis

• Synovial fluid analysis: Gold standard—needle-shaped, negatively birefringent monosodium urate crystals under polarized microscopy.
• Laboratory evaluation: Measure serum urate after acute flare resolution (levels may be normal during flare). Evaluate renal function, lipid profile, glucose, and markers of metabolic syndrome.
• Imaging: Ultrasound (double contour sign) or dual-energy CT for detection of subclinical crystal deposition and tophi.

Management Strategies

Acute flare treatment

• NSAIDs: First-line for most patients (eg, indomethacin, naproxen, celecoxib); contraindicated in peptic ulcer disease or severe renal impairment.
• Colchicine: Low-dose regimens (1.2 mg followed by 0.6 mg) effective if started within 36 hours of flare onset; monitor for GI intolerance.
• Glucocorticoids: Oral (prednisone 0.5 mg/kg/day) or intra-articular injections for patients with contraindications to NSAIDs/colchicine or polyarticular flares.

Urate-lowering therapy (ULT)

Indications: ≥2 flares/year, tophi, CKD stage ≥2, or urate nephrolithiasis.
– Xanthine oxidase inhibitors:
– Allopurinol: Start at 100 mg daily, titrate every 2–4 weeks to achieve serum urate <6 mg/dL (or <5 mg/dL for advanced disease); monitor CBC, LFTs, and renal function; assess for hypersensitivity risk (HLA-B5801 testing in high-risk populations).
– Febuxostat: Alternative when allopurinol intolerant; monitor LFTs and consider cardiovascular risk profile.
– Uricosurics: Probenecid for underexcretors with adequate renal function; avoid in patients with nephrolithiasis.
– Uricase therapies:* Pegloticase for refractory tophaceous gout; IV infusions every 2 weeks; monitor for infusion reactions and antibody development.

Prophylaxis and monitoring

• Flare prophylaxis: Continue low-dose colchicine (0.6 mg daily) or NSAIDs for 3–6 months after ULT initiation to prevent mobilization flares.
• Monitoring: Check serum urate every 2–5 weeks during ULT titration, then every 6–12 months once target achieved. Regularly assess renal and hepatic function.

Lifestyle and comorbidity management

• Diet: Emphasize a balanced diet rich in vegetables, whole grains, and low-fat dairy; limit red meat, seafood, and fructose-sweetened beverages.
• Alcohol: Moderate to low intake; beer and spirits carry higher risk than wine.
• Weight loss: Encourage weight reduction in overweight/obese patients; 5–10% weight loss can lower serum urate.
• Hydration: Adequate fluid intake to reduce crystal formation.
• Comorbidity optimization: Control hypertension, diabetes, dyslipidemia, and obesity to reduce cardiovascular risk.

Special considerations

• CKD patients: Adjust allopurinol dose and consider febuxostat; use uricosurics cautiously.
• Drug interactions: Allopurinol–azathioprine interaction; adjust azathioprine dosing accordingly.
• Patient education: Emphasize medication adherence, recognition of flares, and importance of prophylaxis.

Conclusion

Gout is a highly treatable form of inflammatory arthritis when managed with acute flare control and long-term urate-lowering strategies. Combining pharmacologic therapy with lifestyle modifications and comorbidity management maximizes outcomes and prevents long-term joint damage.