Gout
Gout is a type of crystal arthropathy caused by the deposition of monosodium urate crystals within joints, resulting in episodes of acute inflammatory arthritis.
Causes and Risk Factors
Gout is characterised by the deposition of monosodium urate (MSU) crystals within the joint, which then triggers an inflammatory immune response
- Urate is a metabolite of purines (an essential component of DNA/RNA material)
Hyperuricaemia (high serum urate level) is the most important predisposing factor.
Causes and risk factors by mechanism:
| Causes of impaired renal excretion of urate (more common mechanism) |
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| Causes of increased production of urate |
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| Mixed mechanisms (reduces renal excretion and increases urate production) |
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| Demographic risk factors |
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Importantly, gout may occur even when plasma urate levels are normal, while ~95% of individuals with hyperuricaemia never develop gout.
Clinical Features
Individuals with gout can be asymptomatic:
- Asymptomatic hyperuricaemia, or
- Intercritical gout (symptom-free period between acute gout flares while monosodium urate crystals remain in the joint tissue)
| Acute gout | Rapid onset of severe joint pain
The affected joint is red, swollen, hot, extremely tender, and markedly reduced ROM Acute gout typically causes a monoarticular arthritis. Affected joints include:
Mild systemic upset (e.g. fever, malaise) is possible |
| Chronic gout | Chronic gout usually develops after recurrent or inadequately treated acute gout flares and may present with:
Chronic tophaceous gout: advanced form of gout characterised by presence of tophi + chronic joint damage |
Based on clinical history and examination alone, acute gout can be difficult to distinguish from septic arthritis, as both may present with an acutely painful, red, hot and swollen joint.
The presence or absence of systemic features, such as fever, is NOT reliable to differentiate between them.
Complications
Apart from development of chronic gout (see above), other complications include:
- Permanent joint damage, deformity and functional impairment
- ↑ Risk of urolithiasis (esp. uric acid renal stones)
- Hyperuricaemia is also associated with an increased risk of
- Cardiovascular disease and cardiovascular mortality
- CKD
Investigation and Diagnosis
1st line test: serum urate level (interpreted within the clinical context)
- ≥360 μmol/L or 6 mg/dL confirms the diagnosis of gout
- If serum urate level is below the cut-off and gout is still suspected → repeat the test at least 2 weeks after the flare has settled (as serum urate levels can sometimes drop during an active flare)
Key points in interpreting serum urate levels:
- A typical clinical presentation PLUS elevated serum urate level strongly supports the diagnosis of gout
- An elevated serum urate level alone is not diagnostic of gout, as many patients with hyperuricaemia never develop gout
- A normal serum urate level does not exclude gout
2nd line (if diagnosis remains uncertain after testing serum urate level):
- Joint aspiration for synovial fluid analysis and microscopy
3rd line (if joint aspiration cannot be performed and diagnosis remains uncertain):
- Consider imaging of the affected joint(s) with ultrasound (more sensitive than X-ray) / X-ray / dual-energy CT
NICE recommends measuring serum urate level as the first test in anyone with a typical acute monoarthritis in keeping with gout, due to its non-invasive property, high availability, and low cost
- The NICE committee noted that joint aspiration and synovial fluid analysis remain the ‘gold standard’ test to diagnose gout when the diagnosis remains uncertain
Clinical pearl: A serum urate level alone cannot diagnose or exclude gout. Because acute gout and septic arthritis may present similarly, joint aspiration is often performed together with serum urate measurement when septic arthritis is a possibility
Synovial Fluid Analysis
| Parameter | Finding in Gout |
|---|---|
| Appearance | Cloudy, yellow |
| Viscosity | Reduced |
| WBC count and differential | 2,000 – 50,000 cells/µL with polymorph (neutrophil) predominance |
| Crystals | Needle-shaped monosodium urate crystals with strong negative birefringence |
| Gram stain / culture | -ve |
| Glucose | Normal |
Synovial fluid microscopy in crystal arthropathy
- Gout (monosodium urate crystals): needle-shaped crystals with negative birefringence
- Pseudogout (calcium pyrophosphate crystals): rhomboid-shaped with positive birefringence (pseudogout = positive)
Management
Acute Gout Attack
Conservative management:
- Apply ice to the affected joint
- Continue any pre-existing urate-lowering drugs (allopurinol or febuxostat) – if the patient is taking these medications and has an acute gout attack
Pharmacological management:
- 1st line: NSAID + PPI (e.g naproxen, ibuprofen, but NOT aspirin) OR colchicine OR oral corticosteroid (short-course)
- NICE committee acknowledges that in practice NSAIDs or colchicine is typically 1st line, preferred over corticosteroids
- 2nd line: intra-articular / intramuscular corticosteroid injection
- 3rd line: IL-1 inhibitor (e.g. anakinra, canakinumab) (to be prescribed by specialist)
Some reasons to avoid NSAIDs:
- History of peptic ulcer disease or GI bleed
- Esp. if there is increased risk of GI bleed e.g. concurrent use of anticoagulants
- Chronic kidney disease
- Cardiovascular comorbidity (esp. congestive heart failure and cardiovascular disease)
Some reasons to avoid colchicine:
- Severe renal impairment (in these patients both NSAIDs and colchicine would not be appropriate → oral corticosteroids are more appropriate)
- Intolerance to diarrhoea (common and main side effect of colchicine)
- Severe hepatic impairment
- Concurrent use of strong CYP3A4 or P-glycoprotein inhibitors (e.g. macrolides, ketoconazole, ciclosporin) – increases colchicine concentration and risk of toxicity
Long Term Management
Diet and Lifestyle
- Advise patients to follow a healthy, balanced diet
- At least 5 portions of fruit and vegetables per day
- Low-sugar and low-fat products
- Eat less food that is high in sugar and fat
- Eat more wholegrain starchy food rather than white refined food
- Use healthy cooking methods (e.g. grilling, dry roasting, steaming)
- Advise that excess body weight, obesity, and excessive alcohol consumption may exacerbate gout flares and symptoms
Specific diet advice for gout:
| Food to avoid (high purine food) |
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| Food that can be eaten freely (low purine food) |
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| Beverages |
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Urate-Lowering Therapy (ULT)
| Indications | Discuss the option of ULT to ALL patients who experienced a first or subsequent gout flare
ULT should be offered if ANY of the following are present:
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| Initiating ULT | ULT should be started at least 2-4 weeks after a gout flare has settled
Bridging preventive therapy should be offered to cover the period while ULT is being started and the dose is being titrated until below the target
If ULT is started during the acute gout flare, reducing serum urate levels can destabilise monosodium urate crystals in joint tissues, making the flare worse or prolonged. Exception: if the patient has very frequent flares with no 2-4 weeks of flare-free period → start the ULT during an active flare (along with bridging preventive therapy) |
| Choice of ULT | 1st line: allopurinol or febuxostat (both are xanthine oxidase inhibitors)
In patients with major CVD (e.g. previous MI, stroke, unstable angina):
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| Target | ULT should be offered with a treat-to-target strategy:
Duration of treatment: ULT is typically lifelong (continued even after target serum urate level is reached) |
Do NOT offer ULT to those with high serum urate levels for gout primary prophylaxis (i.e. to prevent a first gout attack in those who never had gout but just a high serum urate level).
Rationale: most patients with hyperuricaemia do NOT actually develop gout.