Gout

Gout occurs when persistently elevated uric acid forms monosodium urate crystals in joints and soft tissues, triggering some of the most intense inflammatory reactions in medicine. The classic attack strikes overnight: a joint — the big toe in half of first attacks — becomes red, hot, swollen and exquisitely tender, sometimes too painful for a bedsheet. Attacks settle over one to two weeks, but without treatment they recur more frequently, involve more joints and eventually form visible tophi and erosive joint damage. Uric acid is the breakdown product of purines, and levels rise through a combination of genetic under-excretion by the kidneys — the dominant driver in most patients — and dietary purine and alcohol load, particularly beer and spirits. This is why gout is strongly hereditary and only partly dietary. Treatment has two arms that are often confused. Acute attacks need rapid anti-inflammatory treatment with NSAIDs, colchicine or steroids. Prevention requires continuous urate-lowering therapy, usually allopurinol, titrated to a target uric acid below 360 micromoles per litre — taken every day indefinitely, including during attacks. Gout also signals metabolic risk: it associates with hypertension, kidney disease and cardiovascular disease and should prompt a broader risk review.

• •Sudden overnight onset of extreme joint pain, classically the big toe
• •Red, hot, swollen joint too tender to touch or bear weight
• •Fever and malaise during severe attacks
• •Attacks settling over 7-14 days, then recurring
• •Increasingly frequent attacks involving ankles, knees, hands and elbows over time
• •Firm chalky deposits (tophi) on ears, fingers, toes and elbows in chronic disease
• •Persistent joint damage and stiffness in untreated long-term gout

• •Genetic renal under-excretion of uric acid — the dominant factor
• •Beer and spirits, which raise urate through production and excretion blockade
• •Purine-rich foods: organ meats, game, anchovies, sardines and shellfish
• •Sugar-sweetened drinks with fructose, which drives urate production
• •Obesity and metabolic syndrome
• •Thiazide and loop diuretics, low-dose aspirin and ciclosporin
• •Chronic kidney disease reducing excretion
• •Dehydration, surgery and acute illness as attack triggers
• •Crash dieting and fasting, which transiently raise urate

Renal under-excretion of uric acid, largely genetically determined, is the primary mechanism in most patients. Dietary purine load, alcohol (which both raises production and blocks excretion), obesity, diuretics and chronic kidney disease add to the burden. When plasma urate exceeds saturation, crystals precipitate in cooler peripheral joints. Neutrophils engulfing crystals trigger the NLRP3 inflammasome and interleukin-1 release, producing the explosive inflammation of an attack.