Gout — Symptoms, Causes & Treatment | MyMedicPlus

Gout is the most common inflammatory arthritis in men, caused by hyperuricemia (elevated serum uric acid) leading to deposition of monosodium urate (MSU) crystals in joints and soft tissues. It affects 1–4% of adults globally, with prevalence increasing with age. The hallmark is exquisitely painful acute arthritis attacks, most typically affecting the first metatarsophalangeal joint (big toe — podagra), followed by pain-free intercritical periods. Without urate-lowering therapy, attacks become more frequent, affect more joints, and lead to chronic tophaceous gout with joint destruction. Untreated gout progresses through four clinical stages: asymptomatic hyperuricaemia, acute gout attacks, intercritical periods, and chronic tophaceous gout. The global burden is rising due to increasing prevalence of obesity, diuretic use, and dietary patterns promoting hyperuricaemia. Gout carries significant comorbidity with cardiovascular disease, metabolic syndrome, and chronic kidney disease, requiring holistic risk factor management beyond urate lowering alone.

Gout results from hyperuricemia — serum urate above 360 µmol/L (6 mg/dL) — from reduced renal urate excretion (90% of cases) or increased production. Dietary triggers include high-purine foods (red meat, organ meats, shellfish), fructose-sweetened beverages, and alcohol (especially beer and spirits). Diuretics (thiazides, furosemide) are the most common medication cause by reducing renal urate excretion. Other risk factors include obesity, hypertension, chronic kidney disease, diabetes, family history, and low-dose aspirin use. Male sex and advanced age are significant risk factors; premenopausal women have partial protection from uricosuric effects of estrogen. Low-dose aspirin (less than 325 mg/day) impairs renal urate excretion despite its cardiovascular benefits. Immunosuppressants including cyclosporine — used after organ transplantation — are a major cause of secondary gout in transplant recipients. Lead nephropathy ('saturnine gout') from occupational or environmental lead exposure causes renal tubular damage reducing urate secretion.

Acute gout attacks present as sudden, severe, excruciating joint pain — typically peaking within 12–24 hours — with marked swelling, warmth, and overlying erythema so intense the skin resembles cellulitis. Even the weight of a bed sheet on the affected joint causes severe pain. The first metatarsophalangeal joint is affected in 50–70% of first attacks (podagra). Other common sites include the ankle, knee, midfoot (tarsus), wrist, and olecranon bursa. Tophi — deposits of urate crystals in soft tissues — appear after years of uncontrolled hyperuricemia as firm, chalky nodules on the ears, elbows, fingers, and Achilles tendon. Tophi may rupture and discharge chalky white material, and can become infected. Between attacks (intercritical period), patients are typically symptom-free, but monosodium urate crystals remain in joints, contributing to chronic inflammation. Systemic features including low-grade fever may accompany acute attacks.

The gold standard for diagnosis is joint aspiration with synovial fluid analysis under polarized light microscopy demonstrating negatively birefringent needle-shaped monosodium urate crystals. However, aspiration is not always practical in acute settings. Clinical diagnosis using the 2015 ACR/EULAR classification criteria is reliable when the presentation is classic. Serum urate may be falsely low during an acute attack (as urate is deposited in joints). Blood tests also assess renal function, CBC, and eGFR. Dual-energy CT (DECT) can detect urate deposits non-invasively. Ultrasound shows the double contour sign (urate coating on cartilage surface) characteristic of gout. The 2015 ACR/EULAR gout classification criteria assign points for clinical features (joint involvement pattern, characteristics of attacks, time course), laboratory findings (serum urate levels), and imaging (double contour sign on ultrasound, urate deposits on DECT). A score of 8 or above has 92% sensitivity and 89% specificity for gout. MRI detects tophaceous deposits and bone erosions in chronic gout.

Acute attacks: NSAIDs (naproxen, indomethacin, diclofenac) are first-line when tolerated, providing pain relief within hours. Colchicine (0.5 mg twice daily or 1 mg initially then 0.5 mg one hour later) is highly effective and preferred in patients with GI issues or renal impairment on low doses. Corticosteroids (oral prednisolone or intra-articular injection) are used when NSAIDs and colchicine are contraindicated. Urate-lowering therapy (ULT): Allopurinol (starting at 50–100 mg daily, titrating to achieve serum urate below 360 µmol/L) is first-line. Febuxostat is an alternative. ULT must not be started during an acute attack — begin 2–4 weeks after the attack resolves with prophylactic colchicine cover during the first 3–6 months. Febuxostat should be used with caution in patients with established cardiovascular disease (CARES trial showed increased cardiovascular mortality vs. allopurinol). Lesinurad (a uricosuric URAT1 inhibitor) in combination with allopurinol is indicated for patients who fail to reach serum urate target on allopurinol alone. Pegloticase — a pegylated recombinant uricase given by IV infusion every 2 weeks — is reserved for refractory tophaceous gout unresponsive to conventional ULT.

Untreated gout progresses to chronic tophaceous gout with permanent joint deformity, destruction of cartilage and bone, and impaired joint function. Urate crystals cause kidney stones (uric acid nephrolithiasis) in 10–25% of gout patients. Gout is an independent risk factor for chronic kidney disease, cardiovascular disease (myocardial infarction, stroke), and metabolic syndrome — sharing common pathophysiological pathways with inflammation and vascular endothelial dysfunction. Septic arthritis (joint infection) must be excluded in every acute hot swollen joint as it can coexist with gout and requires urgent antibiotic treatment.

Dietary modification: reduce high-purine foods (red meat, organ meats, shellfish), eliminate fructose-sweetened beverages and beer, limit spirits and wine. Increase dairy consumption (dairy is uricosuric). Stay well hydrated with water (2–3 L/day). Achieve and maintain healthy body weight. Address modifiable medication causes (switch from thiazide diuretics if possible, avoid low-dose aspirin if not cardiologically indicated). Target serum urate below 360 µmol/L (below 300 µmol/L in tophaceous gout) with allopurinol adjusted every 4 weeks. Annual monitoring of serum urate, renal function, and blood pressure is recommended.

See a GP for: a first episode of an acutely hot, swollen, painful joint — clinical diagnosis of gout is required and septic arthritis (joint infection) must be urgently excluded; gout attacks recurring more than twice a year despite dietary modification; visible tophi (hard chalky deposits on ears, elbows, or fingers); or evidence of uric acid kidney stones. Seek urgent same-day assessment for: a red, hot, swollen joint with fever and systemic illness — this may be septic arthritis, which is a medical emergency requiring urgent joint aspiration, microbiological diagnosis, and IV antibiotics. Do not assume a hot joint is gout without excluding infection, even if you have had gout before (the two can coexist). Seek rheumatology referral for: recurrent gout attacks not controlled by lifestyle modification, tophaceous gout with joint damage, renal impairment with gout (requires specialist allopurinol dose adjustments), and allopurinol hypersensitivity (DRESS syndrome) — where febuxostat or uricosuric agents (probenecid) may be needed.