Write a short note on gout.

Definition

Gout is an inflammatory arthritis caused by deposition of monosodium urate (MSU) crystals in joints and soft tissue, occurring when serum urate exceeds its solubility limit (approximately 6.8 mg/dL). It is the commonest inflammatory arthritis in men, with rising prevalence attributed to diet, obesity, alcohol and diuretic use.

Pathogenesis & Causes

Urate is the end-product of purine metabolism, produced by xanthine oxidase and excreted mainly by the kidney. Hyperuricaemia results from:

• Under-excretion (90%) — chronic kidney disease, diuretics (thiazides, loop), low-dose aspirin, ciclosporin, tacrolimus, ethambutol, pyrazinamide, alcohol (especially beer), lead nephropathy, dehydration, hypothyroidism.
• Over-production (10%) — high purine diet (red meat, organ meat, shellfish), fructose-sweetened drinks, alcohol, myeloproliferative and lymphoproliferative disorders, tumour lysis syndrome, psoriasis, haemolysis, and enzyme defects (Lesch–Nyhan syndrome — HGPRT deficiency).

Not all hyperuricaemic patients develop gout, and urate may be normal during an acute attack — so a normal level does not exclude the diagnosis.

Clinical Features

Acute gout:

• Sudden, severe monoarthritis, characteristically waking the patient in the early hours.
• Podagra — the first metatarsophalangeal joint — is involved in over 50% of first attacks and eventually in most patients.
• The joint is exquisitely tender, red, hot and swollen, with overlying skin desquamation as the attack settles; even bedclothes are intolerable.
• Untreated attacks resolve spontaneously over 7–10 days.
• Triggers: alcohol binge, purine-rich meal, dehydration, surgery, trauma, infection, starvation, and initiation of urate-lowering therapy.

Chronic tophaceous gout: after years of untreated disease — tophi (firm, chalky white urate deposits) on the helix of the ear, olecranon bursa, extensor forearm, Achilles tendon and fingers; chronic destructive arthropathy with "punched-out" para-articular erosions with overhanging edges on X-ray, and preserved joint space until late.

Renal complications: urate nephrolithiasis, chronic urate nephropathy, and acute urate nephropathy in tumour lysis syndrome.

Investigations

• Synovial fluid aspiration and polarised light microscopy — the gold standard. MSU crystals are needle-shaped and NEGATIVELY birefringent, appearing yellow when parallel to the axis of the compensator, and are seen within neutrophils during an attack.
• Always send synovial fluid for Gram stain and culture — septic arthritis can coexist with, and clinically mimic, acute gout.
• Serum urate — best measured 2 weeks after the attack subsides, since it falls during acute inflammation.
• CBC (leucocytosis), ESR and CRP raised; renal function; fasting glucose and lipids (metabolic syndrome is strongly associated).
• X-ray — normal early; later shows punched-out erosions with sclerotic margins and overhanging edges. Ultrasound shows the "double contour sign" of urate deposited on cartilage; dual-energy CT identifies urate deposits non-invasively.
• 24-hour urinary urate to distinguish over-producers from under-excretors in selected cases.

Management

Acute attack — treat promptly, and do not start or stop urate-lowering therapy during the attack:

• NSAIDs at full anti-inflammatory dose (avoid in renal impairment, peptic ulcer, heart failure).
• Colchicine — effective, particularly if started early; limited by diarrhoea and by toxicity in renal impairment. Low-dose regimens are as effective as, and better tolerated than, older high-dose schedules.
• Corticosteroids — oral, intra-articular or intramuscular; the agent of choice where NSAIDs and colchicine are contraindicated, especially in renal disease and the elderly.
• IL-1 inhibitors (anakinra, canakinumab) for refractory cases.
• Rest and elevate the joint; continue any existing urate-lowering drug unchanged.

Long-term urate-lowering therapy — indications: recurrent attacks (two or more per year), tophi, chronic gouty arthropathy, radiographic erosions, urate nephrolithiasis, and gout with chronic kidney disease.

• Allopurinol — a xanthine oxidase inhibitor and first-line agent. Start at a low dose and titrate upwards against serum urate. Reduce dose in renal impairment. Risks include rash and rarely severe cutaneous adverse reactions (DRESS, SJS/TEN), associated with HLA-B*5801, which is more prevalent in some Asian populations.
• Febuxostat — alternative xanthine oxidase inhibitor, useful in allopurinol intolerance.
• Uricosurics (probenecid) — increase renal excretion; avoid where there is nephrolithiasis or renal impairment.
• Target serum urate below 6 mg/dL (below 5 mg/dL where tophi are present) — treat to target, not to symptoms.
• Prophylaxis with low-dose colchicine or NSAID for the first several months of urate-lowering therapy, because falling urate mobilises crystals and precipitates attacks — the commonest reason patients abandon treatment.

Lifestyle: weight reduction, reduced alcohol (especially beer and spirits), avoidance of fructose-sweetened drinks and excess red and organ meat, adequate hydration, and review of diuretics — losartan and calcium channel blockers lower urate and are preferred antihypertensives in gout.