Gout — Causes, Symptoms, Uric Acid & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Gout is an intensely painful inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints, periarticular tissues, and soft tissues, resulting from sustained hyperuricaemia (elevated serum uric acid). It is the most common inflammatory arthritis in adults globally, affecting approximately 3-4% of the adult population, with a 4:1 male predominance — women are relatively protected by oestrogen (which has a uricosuric effect) until menopause. The natural history of untreated gout progresses through four stages: asymptomatic hyperuricaemia, acute intermittent gout (episodic attacks), intercritical gout (asymptomatic periods between attacks), and chronic tophaceous gout (urate crystal deposits visible as tophi, joint destruction, and chronic pain). Gout is strongly associated with cardiovascular disease, chronic kidney disease, hypertension, metabolic syndrome, and type 2 diabetes — treating gout reduces cardiovascular risk as well as joint damage.

Hyperuricaemia arises from overproduction or underexcretion of uric acid (urate), or both. Urate is the end-product of purine metabolism — the enzyme xanthine oxidase converts xanthine to uric acid. Overproduction causes: high purine intake (red meat, organ meat, seafood, alcohol — especially beer), rapid cell turnover (haematological malignancies, psoriasis, chemotherapy), and genetic enzyme defects (Lesch-Nyhan syndrome — severe HPRT deficiency). Underexcretion (most common mechanism in primary gout — 90% of cases): impaired renal urate clearance — genetic variants in urate transporters URAT1 (SLC22A12) and GLUT9; chronic kidney disease; medications — thiazide and loop diuretics (major cause), ciclosporin, low-dose aspirin, pyrazinamide; dehydration. Triggers for acute attacks: alcohol binge (acute hyperuricaemia from ATP breakdown and lactic acid competing with urate excretion), purine-rich meal, fasting or crash diet, surgery, illness, IV contrast, and starting urate-lowering therapy (ULT) without colchicine cover (mobilises crystals from established deposits).

Acute gout attack: sudden onset (often overnight) of severe, excruciating pain in the affected joint — described as the worst pain experienced; the joint is hot, swollen, erythematous, and exquisitely tender (even light touch of bed sheet causes agony). The first metatarsophalangeal (MTP) joint (big toe) is the classic site — 'podagra' — involved in 70-80% of first attacks. Other common sites: ankle, knee, wrist, elbow, and finger joints. Attacks peak within 24-48 hours and self-resolve within 5-14 days untreated; less severe in early disease. Tophi: firm, irregular nodules of urate crystals deposited in skin, periarticular tissue, tendons (Achilles tendon, patellar tendon), and pinnae of the ears in chronic tophaceous gout — may ulcerate and discharge white chalky material. Chronic tophaceous gout: chronic joint pain and structural joint damage from persistent urate deposition — can mimic rheumatoid arthritis. Associated features: hypertension, obesity, renal stones (uric acid and calcium oxalate), and chronic kidney disease.

Clinical diagnosis is appropriate in typical presentations (first MTP joint, male, hyperuricaemia, alcohol history). However, joint aspiration and synovial fluid analysis is the definitive diagnostic method: monosodium urate crystals appear as negatively birefringent needle-shaped crystals under polarised light microscopy — pathognomonic of gout. Serum uric acid (urate): elevated above 360 mcmol/L (6 mg/dL) in most patients, but can be normal during an acute attack (due to redistribution into crystals) — a normal urate level does not exclude gout. Always repeat urate measurement 2-4 weeks after an acute attack for baseline. Blood tests: FBC (leucocytosis during attack), CRP and ESR (elevated, may be very high — occasionally mimicking septic arthritis), renal function and eGFR, and lipids. Imaging: plain X-rays show soft tissue swelling acutely; chronic tophaceous gout shows characteristic 'overhanging edge' erosions. Ultrasound: urate crystal deposition as 'double contour sign' on articular cartilage — highly specific for gout. Dual-energy CT (DECT): identifies urate deposits before tophi are clinically apparent. Synovial fluid Gram stain and culture: to exclude septic arthritis (which can coexist).

Acute attack management: RICE (rest, ice, elevation) plus pharmacotherapy. Colchicine: first-line if started within 24 hours of attack onset — 0.5 mg twice or three times daily (NICE 2022 low-dose regimen is safer than high-dose historical protocols); avoid in severe renal impairment. NSAIDs: naproxen 500 mg twice daily or indomethacin — avoid in CKD, peptic ulcer disease, and CV disease (concurrent PPI). Corticosteroids: oral prednisolone 30-35 mg/day for 5 days — for those in whom NSAIDs and colchicine are contraindicated; also intra-articular methylprednisolone for monoarthritis. Urate-lowering therapy (ULT) — indicated after: 2 or more gout attacks per year, tophi, uric acid nephrolithiasis, CKD Stage 3+, or radiographic damage. Target serum urate below 360 mcmol/L (300 mcmol/L for tophaceous disease). Allopurinol: xanthine oxidase inhibitor — first-line ULT; start at 50-100 mg/day and titrate slowly (reduce dose in renal impairment); HLA-B*5801 testing before starting in high-risk populations (South-East Asian and Han Chinese — risk of severe cutaneous reactions). Febuxostat: alternative xanthine oxidase inhibitor for allopurinol-intolerant patients; not recommended in cardiovascular disease (FAST trial: higher cardiovascular event rate vs allopurinol). Pegloticase: IV recombinant uricase for severe tophaceous gout refractory to oral ULT. Prophylactic colchicine (0.5 mg daily for 3-6 months) during initiation of ULT prevents mobilisation flares.

Untreated or inadequately controlled gout progresses to chronic tophaceous gout — the deposition of large monosodium urate crystal aggregates (tophi) in joints, tendons, bursae, and subcutaneous tissues causing disfigurement, chronic pain, and progressive joint destruction that can be severe enough to mimic rheumatoid arthritis radiographically, with irreversible joint damage once established. Uric acid nephrolithiasis (kidney stones) affects approximately 20% of patients with gout — uric acid stones are radiolucent (not visible on plain X-ray) and can cause renal colic, hydronephrosis, and recurrent urinary tract infections progressing to chronic kidney disease. Gouty nephropathy from urate crystal deposition in the renal parenchyma contributes to progressive renal impairment in severe tophaceous disease, further impairing renal urate excretion and creating a cycle of worsening hyperuricaemia. Cardiovascular disease risk is significantly elevated in gout patients — independent of traditional cardiovascular risk factors — driven by systemic inflammation, endothelial dysfunction, and the high prevalence of coexisting metabolic syndrome, hypertension, and chronic kidney disease. Tumour lysis syndrome during haematological malignancy chemotherapy can cause massive urate release, acute hyperuricaemia, and acute tubular necrosis from urate crystal precipitation in renal tubules — a medical emergency requiring rasburicase (recombinant uricase), aggressive IV hydration, and urinary alkalinisation.

Long-term ULT at adequate doses is the cornerstone of gout prevention — approximately 50% of patients with gout do not take their ULT medication regularly. Maintain target serum urate (below 360 mcmol/L) — regular monitoring and dose adjustment are required. Dietary modifications with modest impact: reduce red meat, organ meat, and shellfish; avoid alcohol especially beer (high purine content from yeast; also impairs urate excretion); avoid high-fructose corn syrup beverages. Low-fat dairy products may be mildly uricosuric. Coffee consumption is associated with lower gout risk. Hydration: good fluid intake (2-3 L/day) promotes renal urate excretion. Weight loss reduces urate levels — each 1 BMI unit reduction decreases serum urate. Review and change precipitating medications where possible: replace thiazide diuretics with alternatives if clinically safe; use losartan (uricosuric) rather than other ARBs for hypertension management in gout patients. Vitamin C supplementation has modest uricosuric effects.

Seek emergency care if a hot, swollen joint is accompanied by fever and systemic upset — septic arthritis can coexist with gout and is a joint-destroying emergency requiring urgent joint aspiration, Gram stain, culture, and empirical IV antibiotics. Never assume a hot joint is 'just gout' without excluding infection. See your GP promptly for any first episode of joint inflammation, recurrent gout attacks (even if self-resolving), or if you are using thiazide diuretics or other medications known to precipitate gout. Any patient with 2 or more gout attacks per year, tophi, or kidney stones requires urate-lowering therapy — many patients are undertreated. Gout associated with renal impairment needs nephrology input. Discuss cardiovascular risk factor management (hypertension, dyslipidaemia, diabetes) with your doctor, as gout significantly increases cardiovascular disease risk.