Gout
Exam Tips
- In any hot swollen joint, exclude septic arthritis first; fever may be absent.
- Serum urate can be normal during an acute flare, so repeat after 2-4 weeks if suspicion persists.
- Gold standard diagnosis is MSU crystals in aspirate (needle-shaped, negatively birefringent).
- Podagra plus abrupt overnight onset and previous similar self-limiting attacks is highly suggestive.
- Tophi imply longstanding crystal burden and indicate need for aggressive urate-lowering strategy.
- Safety: avoid/limit NSAIDs in CKD, peptic ulcer disease, heart failure, or anticoagulation risk; colchicine toxicity risk increases with renal impairment and CYP3A4/P-gp inhibitors (for example clarithromycin); screen high-risk ethnic groups for allopurinol hypersensitivity risk where local policy recommends.
Definition
Gout is an inflammatory crystal arthropathy caused by deposition of monosodium urate (MSU) crystals in and around joints, typically presenting with abrupt episodes of severe arthritis (often overnight). It classically affects the first metatarsophalangeal joint (podagra), but can involve ankles, knees, midfoot, wrists, fingers, and elbows; untreated disease may progress from intermittent flares to chronic tophaceous joint damage.
Pathophysiology
At physiological pH, uric acid circulates mainly as urate; persistent hyperuricaemia increases supersaturation and promotes MSU crystal formation, especially in cooler peripheral joints. Around 70% of urate is cleared renally and about 30% via the gut, so reduced renal excretion is the dominant mechanism in most patients, with a smaller group having overproduction (for example high cell turnover or genetic purine pathway disorders). Crystal shedding into synovium triggers innate immunity (macrophage uptake, NLRP3 inflammasome activation, IL-1beta release, neutrophil recruitment), producing the rapid-onset intensely painful flare. Repeated crystal-driven inflammation causes erosive damage and tophus formation in soft tissue (for example ear helix, olecranon region, Achilles tendon). See Figure: classic podagra and auricular tophi in rheumatology image atlases.
Risk Factors
- Chronic kidney disease and reduced renal urate excretion
- Hypertension, diabetes mellitus, hyperlipidaemia, osteoarthritis
- Obesity or excess body weight
- Alcohol excess (especially beer/spirits), sugary drinks, high purine intake (red meat, seafood)
- Male sex, older age, postmenopausal status in women
- Family history of gout/hyperuricaemia/nephrolithiasis
- Medicines: diuretics (thiazide/loop), low-dose aspirin, ciclosporin
- Myeloproliferative/lymphoproliferative disorders, severe psoriasis
- Genetic/metabolic disorders causing urate overproduction (for example Lesch-Nyhan, glycogen storage disease)
Clinical Features
Symptoms
- Sudden severe monoarticular pain (often maximal within 24 hours), frequently overnight
- Marked joint tenderness with inability to tolerate touch or weight-bearing
- Recurrent self-limiting attacks lasting about 5-15 days if untreated
- Intercritical symptom-free periods between flares
- Chronic inflammatory joint pain/stiffness in advanced disease
- Functional limitation affecting mobility, work, and sleep
Signs
- Hot, red, swollen joint (classically first MTP: podagra)
- Lower-limb predominance (first MTP, midfoot, ankle, knee), but any joint can be involved
- Tophi: firm white/yellow subcutaneous nodules over extensor surfaces, Achilles tendon, helix of ear, dorsum of hands/feet
- Reduced range of movement during acute inflammation
- Overlying skin desquamation/pruritus as flare resolves
- Usually monoarthritis, but oligoarticular/polyarticular presentations can occur
Investigations
Management
Lifestyle Modifications
- Weight reduction if overweight; regular exercise within pain limits
- Reduce alcohol intake (especially beer/spirits) and fructose-sweetened drinks
- Moderate high-purine foods (red meat, some seafood); encourage balanced Mediterranean-style diet
- Good hydration and cardiovascular/renal risk-factor optimisation
- Review contributory medicines where possible (for example consider alternatives to thiazide/loop diuretics)
Pharmacological Treatment
Acute flare treatment
- Naproxen 750 mg stat, then 250 mg every 8 hours until attack settles + gastroprotection if indicated
- Colchicine 500 micrograms 2-4 times daily (max 6 mg per course)
- Prednisolone 30-35 mg once daily for 5 days (if NSAID/colchicine unsuitable)
Start treatment as early as possible. Do not use NSAID plus colchicine routinely together. If already on urate-lowering therapy (ULT), continue it during flare.
Urate-lowering therapy (long-term)
- Allopurinol 100 mg once daily initially (lower start if CKD), titrate every few weeks to target urate; usual max 900 mg/day
- Febuxostat 80 mg once daily, increase to 120 mg once daily if target not achieved
Indicated for recurrent flares, tophi, CKD, urate nephrolithiasis, or chronic gout. Treat-to-target serum urate < 360 micromol/L (often < 300 micromol/L in severe tophaceous disease). Give flare prophylaxis when initiating ULT.
Flare prophylaxis during ULT initiation
- Colchicine 500 micrograms once or twice daily
- Alternative: low-dose NSAID with PPI cover if colchicine not tolerated
Commonly continued for up to 6 months after starting ULT to reduce mobilisation flares.
Surgical / Interventional
- Aspiration/intra-articular corticosteroid injection for selected flares after excluding sepsis
- Tophus debulking or excision when severe mechanical impairment, ulceration, recurrent infection, or major functional/cosmetic impact
Complications
- Recurrent flares progressing to chronic gouty arthritis
- Tophi with deformity, ulceration, secondary infection, and disability
- Irreversible joint damage and reduced quality of life
- Urate nephrolithiasis
- Association with CKD progression
- Increased cardiovascular comorbidity burden (for example hypertension, heart failure, stroke, MI)
Prognosis
A single acute flare usually settles spontaneously within 5-15 days, but recurrence is common without ULT and risk rises year-on-year after the first attack. Long-term control is generally good with early flare treatment, sustained urate-lowering to target, and comorbidity management; delayed or inadequate treatment increases risk of chronic pain, tophi, and joint destruction.
Sources & References
🏥BMJ Best Practice(1)
💊BNF Drug References(16)
- Aspirin[cautions]
- Bendroflumethiazide[cautions]
- Bismuth subsalicylate[cautions]
- Chlortalidone[cautions]
- Co-amilofruse[cautions]
- Furosemide with triamterene[cautions]
- Hydrochlorothiazide[cautions]
- Indapamide[cautions]
- Inosine pranobex[cautions]
- Methenamine hippurate[contraindications]
- Metolazone[cautions]
- Nicotinic acid[cautions]
- Pyrazinamide[cautions]
- Ribavirin[cautions]
- Triamterene[cautions]
- Xipamide[cautions]
✅NICE Guidelines(1)
- Gout[overview]