Lucan · Conditions

Gout

Australian guidance: eTG Rheumatology — Gout + RACGP

1. Definition and epidemiology

Gout is a chronic disease caused by the deposition of monosodium urate (MSU) crystals in joints, soft tissues, and kidneys, arising from sustained hyperuricaemia (serum uric acid above approximately 0.42 mmol/L). The prevalence of gout is increasing in Australia and New Zealand, driven by an ageing population, rising obesity rates, increased alcohol and fructose-sweetened drink consumption, and a higher burden of metabolic comorbidities. Indigenous Australians, Aboriginal and Torres Strait Islander peoples, Maori, and Pacific peoples carry a disproportionately higher prevalence than the general Australian community. Gout is rare before menopause in women and before adulthood in men; a diagnosis of gout in a child requires a demonstrable genetic defect in urate metabolism.

2. Pathophysiology

Uric acid is the end product of purine catabolism in humans, generated via xanthine oxidase from hypoxanthine and xanthine. Humans lack uricase and therefore cannot convert uric acid to the more soluble allantoin, making sustained hyperuricaemia inevitable when excretion is impaired. Approximately two-thirds of uric acid is eliminated by the kidneys and one-third by the gut. Underexcretion accounts for the majority of cases and is worsened by thiazide diuretics, loop diuretics, and ciclosporin, all of which inhibit renal tubular urate transport. Overproduction occurs with high dietary purine intake (meat and seafood), alcohol (especially beer and spirits), fructose-sweetened drinks, and conditions of high cell turnover such as haematological malignancies and severe psoriasis (Robbins Ch 26).

When serum urate exceeds the saturation threshold, MSU crystals nucleate and deposit in avascular tissues including articular cartilage. Free intra-articular MSU crystals are phagocytosed by synovial macrophages and neutrophils, triggering NLRP3 inflammasome activation and caspase-1 cleavage of pro-IL-1beta to its active form. This drives a self-amplifying neutrophilic cascade producing the acutely painful gouty flare. Repeated, untreated attacks lead to progressive tophaceous crystal deposition, osteoclast-mediated joint erosion, and chronic arthropathy (Robbins Ch 26). Comorbidities including obesity, hypertension, chronic kidney disease, dyslipidaemia, and type 2 diabetes are both risk factors and consequences of gout, each compounding cardiovascular risk.

3. Clinical presentation and diagnostic criteria

Acute gout presents as a sudden-onset, severely painful monoarthritis, typically beginning at night or in the early morning, reaching peak intensity within 6 to 24 hours. The first metatarsophalangeal joint (podagra) is the most commonly affected site; the midfoot, ankle, knee, and wrist are also frequently involved. The joint is red, swollen, warm, and exquisitely tender. Systemic features including fever, leucocytosis, and elevated inflammatory markers are common and can closely mimic septic arthritis, which must be actively excluded. Untreated acute attacks typically resolve spontaneously over days to two weeks.

In women, the first attack may be polyarticular, typically affecting the hands, and may be superimposed on osteoarthritic joints; the presence of tophi and acute onset distinguishes gout from an osteoarthritis flare. Most patients who are not commenced on urate-lowering therapy will have a second attack within two years, with subsequent attacks becoming more frequent, more prolonged, and involving more joints over time.

Chronic gouty arthritis develops when recurrent attacks fail to resolve fully. Gouty tophi, which are firm subcutaneous deposits of MSU, occur characteristically at the olecranon bursae, prepatellar bursae, peripheral joints of the fingers and toes, and the ear helix. Chronic tophaceous gout causes progressive destructive arthropathy.

Definitive diagnosis requires identification of MSU crystals (negatively birefringent, needle-shaped, under polarised light microscopy) in synovial fluid, bursal fluid, or tophus aspirate. Joint aspiration is the gold standard and should also be sent for microscopy and culture to exclude septic arthritis. Where aspiration is not feasible, a clinical diagnosis is supported by monoarthritis at the first MTP joint or foot, rapid peak onset, erythema, history of similar attacks, tophi, strong family history, and cardiovascular disease with hyperuricaemia in a male or post-menopausal female.

4. Investigations and AU-specific cutoffs

Synovial fluid microscopy and culture is the gold standard investigation and is mandatory on first presentation to exclude septic arthritis. Serum uric acid should be measured in all patients with suspected gout, but may be spuriously low during an acute attack; if normal during an acute attack, repeat measurement two to four weeks after resolution. The eTG Rheumatology treat-to-target framework uses a serum uric acid below 0.36 mmol/L (6 mg/dL) as the standard target for patients with non-tophaceous gout, and below 0.30 mmol/L (5 mg/dL) initially for patients with tophi, chronic arthropathy, or frequent attacks, until crystal dissolution is achieved.

Renal function (serum creatinine, eGFR) must be measured at baseline because chronic kidney disease is both a risk factor and a consequence of gout, and it influences drug choice and dosing. Further baseline investigations include fasting glucose or HbA1c, fasting lipid profile, and full blood count.

Plain X-ray is used to identify joint damage (periarticular erosions with overhanging edges, the "rat-bite" sign) and preserved joint space; radiographic damage at any stage is an indication to commence urate-lowering therapy. Ultrasound can demonstrate the double contour sign of urate crystal deposition on articular cartilage. Dual-energy CT is the most sensitive imaging modality for tophaceous deposits but does not replace joint aspiration.

5. Management

Management has two distinct phases: rapid relief of the acute attack, and long-term urate-lowering therapy to dissolve existing crystals and prevent recurrence.

For the acute attack, treatment should be started as soon as possible after onset. Per eTG Rheumatology, NSAIDs, low-dose colchicine, and corticosteroids (local or systemic) are equally effective first-line options; drug choice is individualised to comorbidities, renal function, and potential drug interactions. NSAIDs are often preferred in younger patients with no cardiovascular, renal, or gastrointestinal contraindications. Corticosteroids have a lower rate of acute adverse effects than NSAIDs and can be used safely across a broader range of comorbidities. Intra-articular corticosteroid injection is appropriate when one or two joints are affected and infection has been excluded; the injection can be given before culture results are available unless penetrating trauma recently occurred. Colchicine is reserved for patients who have previously used it successfully for an acute flare; it is unlikely to be effective if not started within 24 hours of the attack.

Lifelong urate-lowering therapy is recommended for all patients with a confirmed diagnosis of gout. The decision to commence therapy is most urgent in patients with tophi, radiographic damage, two or more flares annually, or significant kidney impairment with elevated serum urate and nephrolithiasis. It is safe to commence urate-lowering therapy during treatment of an acute attack. Dose titration follows a treat-to-target approach with monthly serum urate monitoring during dose escalation, then six-monthly once the target is achieved. Flare prophylaxis must accompany dose initiation and any dose increases, because rapid changes in serum urate concentration trigger flares. Patients should be explicitly counselled not to stop or reduce urate-lowering therapy during an acute flare, as this worsens the attack.

Lifestyle modifications should address modifiable risk factors: reduce purine-rich foods (meat, organ meat, shellfish), minimise alcohol especially beer and spirits, eliminate fructose-sweetened drinks, achieve a healthy weight, exercise regularly, and stay well hydrated. Where a causative drug (e.g. thiazide diuretic) cannot be substituted, its contribution to hyperuricaemia is managed pharmacologically.

6. Pharmacology and AU PBS notes

Allopurinol is the first-line urate-lowering agent and is PBS-listed in Australia (general benefit, no authority required for confirmed gout). It is a xanthine oxidase inhibitor that reduces uric acid production. The starting dose is 50 mg daily, with up-titration by 50 mg every two weeks or 100 mg every four weeks to a maximum of 900 mg daily, titrated to achieve the serum urate target. Many patients require doses above 300 mg daily. Kidney impairment is not a contraindication; the same or lower starting dose and a slower up-titration rate with close renal monitoring are recommended. Allopurinol inhibits metabolism of azathioprine and mercaptopurine, substantially increasing bone marrow toxicity risk; if the combination cannot be avoided, azathioprine or mercaptopurine doses must be reduced to approximately one-quarter to one-third and the full blood count monitored closely. Allopurinol hypersensitivity syndrome (erythematous desquamating rash, fever, hepatitis, eosinophilia, worsening renal function) is rare but potentially fatal; risk factors include high starting dose, rapid up-titration, kidney impairment, older age, and HLA-B*5801 carriage, which is more prevalent in Han Chinese, Korean, and Thai populations. Patients should stop allopurinol immediately and seek review if any skin rash develops.

Flare prophylaxis with colchicine 500 micrograms orally daily is the preferred regimen when initiating or increasing urate-lowering therapy, continued for at least six months. NSAIDs or low-dose oral corticosteroids are alternatives if colchicine is contraindicated or ineffective.

Febuxostat (a non-purine selective xanthine oxidase inhibitor) is second-line and is PBS-listed as a Restricted Benefit Authority for patients with a contraindication or intolerance to allopurinol. Dosing is 40 mg daily, increasing by 40 mg every two to four weeks to a maximum of 80 mg daily (120 mg approved internationally). Febuxostat is not recommended in patients with pre-existing major cardiovascular disease; use with caution in moderate to severe kidney or hepatic impairment. Like allopurinol, it interacts with azathioprine and mercaptopurine.

Probenecid (a uricosuric) is an alternative second-line agent (250 mg twice daily, increasing to a maximum of 2 g daily in divided doses) in patients who cannot tolerate xanthine oxidase inhibitors. It is contraindicated in urate nephrolithiasis and requires an eGFR above 50 mL/min/1.73m² for meaningful efficacy. It may be added to allopurinol if the serum urate target is not achieved despite confirmed adherence.

7. Complications and monitoring

Joint complications from untreated or undertreated gout include progressive periarticular erosion, tophaceous deposits causing tendon rupture, and chronic disabling arthropathy with permanent deformity. Renal complications include urate nephropathy from parenchymal crystal deposition and uric acid nephrolithiasis. Gout carries significantly elevated cardiovascular risk through its association with hypertension, type 2 diabetes, dyslipidaemia, obesity, and chronic kidney disease; these comorbidities require active concurrent management.

Serum urate should be measured monthly during dose titration of urate-lowering therapy. Once the target is achieved, measure at six months then annually. Renal function is checked at baseline and after each dose change. Liver biochemistry is monitored at baseline and periodically in patients on febuxostat. Full blood count is monitored in patients on probenecid and in those on allopurinol combined with azathioprine or mercaptopurine. Tophi size should be examined clinically at each review; progressive tophus shrinkage over months to years confirms effective serum urate control. Patients should be informed that urate-lowering therapy is often lifelong, and that flares early in treatment are a predictable consequence of crystal mobilisation and do not indicate treatment failure. Nonadherence is the most common cause of treatment failure before considering dose escalation.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.