Gout

The British Society for Rheumatology Guideline for the Management of Gout (2017)

 

BMJ Publication. 2016 updated EULAR evidence-based recommendations for the management of gout


Definition

  1. Gout is a disorder of purine metabolism characterized by a raised uric acid level in the blood (hyperuricaemia) and the deposition of urate crystals in joints and other tissues or the urinary tract.

  2. Gout may present without hyperuricaemia, and hyperuricaemia may occur without gout.

  3. Hyperuricaemia is an independent risk factor for cardiovascular and chronic kidney disease after adjusting for traditional cardiovascular risk factors.


Prevalence

The prevalence of gout was 2.49%
The incidence of gout was 1.77 per 1000 person years.
The overall ratio of men to women was 4.3:1.


Pathology

The natural history of gout can occur in three distinct phases:

  1. A long period of asymptomatic hyperuricaemia.

  2. A period during which acute attacks of gouty arthritis are followed by variable intervals (months to years) when there are no symptoms.
    Acute attacks of gout usually completely subside in 1-2 weeks without treatment. However, attacks may recur.

  3. The final period of chronic tophaceous gout, where people have nodules affecting joints.


Risk factors

About 90% of people with hyperuricaemia are under-excretors of urate, about 10% are over-producers of urate.

Onset of gout in a person younger than 30 years of age suggests renal or enzymatic disorders and is often associated with genetic causes

Primary hyperuricaemia (diet, family history)

Secondary hyperuricaemia:
Hypertension
Hyperparathyroidism, Sarcoidosis
Chronic renal disease
Glycogen storage diseases, lymphoproliferative/myeloproliferative disorders, carcinomatosis, polycythaemia and severe psoriasi, Down's syndrome, lead nephropathy

Drugs: beta-blockers, ACE inhibitors, diuretics and non-losartan angiotensin II receptor antagonists increase the risk of gout,
whereas calcium channel blockers and losartan reduce the risk (i.e. consider losartan as the preferred antihypertensive agent)


Consequences

  • Arthritis

  • Tophi

  • Urinary stones

  • Gout is an independent risk factor for chronic kidney disease, myocardial infarction and cardiovascular disease mortality


Diagnosis

The only way to definitively distinguish septic arthritis from acute gout is to aspirate the affected joint prior to starting antibiotics, and arrange crystal examination, Gram stain, and culture of aspirated fluid

  1. Exclude septic arthritis
    Systemically unwell (with or without a temperature) and an acutely painful, hot, swollen joint.
    Aspiration of joint fluid is required if septic arthritis is suspected.)

  2. Clinical history and examination.
    Gout typically affects the first metatarsophalangeal joint (big toe) — and midfoot, ankle, knee, fingers, wrist and elbow joints, although can effect any joint. 
    Lower limb joints are affected more frequently than upper limb joints.
    Severe joint pain with associated swelling, redness, warmth and tenderness usually reaches maximum intensity within 24 hours.

Overall, septic arthritis tends to have a less acute onset of pain/swelling (compared to gout with onset within 24hr) and may have heightened markers of inflammation (WBC, ESR, CRP) and fever. As a result traditional markers of infection are not useful to distinguish septic arthritis from acute gout.


Consider primary care investigations

  1. Joint fluid microscopy and culture: Provides a definitive diagnosis if urate crystals are observed in synovial fluid or tophi.

  2. Serum uric acid (SUA) is usually measured 4–6 weeks after an acute attack of gout to confirm hyperuricaemia:

  3. The formation and deposition of monosodium urate crystals occur when urate levels are persistently above 380 micromol/L.

  4. Joint X-ray: Plain radiographs are often normal.

  5. Screening cardiovascular risk factors (diabetes, hypertension, hyperlipidaemia) and renal disease

Differential diagnosis

  • Septic arthritis:

  • Bursitis, cellulitis, tenosynovitis.

  • Non-urate crystal-induced arthropathy, such as pseudogout

  • Osteoarthritis

  • Psoriatic arthritis

  • Reactive arthritis

  • Rheumatoid arthritis

  • Haemochromatosis

  • Trauma


Management of Acute Gout

If septic arthritis or osteomyelitis is suspected
URGENTLY REFER to a rheumatologist or an orthopaedic surgeon for emergency joint aspiration and culture.

  1. Treat acute attack
    1st line

    Oral NSAID PLUS PPI
    OR
    Oral colchicine (500 micrograms orally two to four times daily until symptoms are relieved, up to a maximum of 6 mg per course).

    2nd line
    Short course of oral corticosteroids (oral prednisolone 30-40 mg daily, tapering to nothing by 7-14 days; anecdotally 20mg dose achieves same effect)
    or single im corticosteroid (useful option in patients with oligoarticular or polyarticular attacks)
    or intra-articular corticosteroid (very effective treatment for monoarticular attacks).

  2. Do not stop allopurinol or febuxostat during an acute attack of gout if the person is already established on these drugs.

  3. SAFETY-NETTING:
    If symptoms get worse or if there is an inadequate response to treatment after 1-2 days: return for medical review (if appropriate, consider an alternative diagnosis)

  4. After an acute attack of gout has resolved, follow up the person after 4–6 weeks, and:

    • Measure the serum uric acid level and renal function

    • Assess cardiovascular risk factors (obesity, hypertension, lipids, diabetes)

    • Assess predisposing lifestyle factors (diet, exercise, alcohol, sugary drinks)

    • Review medications such as diuretics.

Pseudogout and Reactive Arthritis

Non-infective causes of an acute hot swollen joint such as Pseudogout calcium pyrophosphate crystal deposition or reactive arthritis will also respond to NSAIDs, low dose colchicine, or corticosteroids.

Joint aspiration and intra-articular corticosteroid administration

Intra-articular aspiration and corticosteroid injection ( if infection is not a concern) are highly effective in acute monoarticular gout and may be the treatment of choice in patients with acute gout in a large joint and comorbidity. Furthermore, joint aspiration provides an an opportunity to confirm a diagnosis of acute crystal arthritis.
However, the treatment requires specialist skills that may not be readily available in primary care.


Management of Preventing Gout: Urate-lowering therapy (ULT)

Offer ULT

  • Recurrent acute attacks of gout

  • The presence of tophi

  • Evidence of joint damage on x ray

  • Renal impairment

  • Uric acid urolithiasis

  • Use of diuretic therapy

  • Primary gout starting at a young age.

Initiating and monitoring ULT treatment

  1. Allopurinol or febuxostat should be started 1-2w after the attack has settled (3w after an acute attack)

  2. 1st line ULT Allopurinol (caution if patient has underlying chronic kidney disease)
    Start at a low dose Allopurinol 100mg and titrate upwards (where tolerated) every four weeks until the serum uric acid (SUA) level is below 300 micromol/L.

    2nd Line ULT Febuxostat (if allopurinol is not tolerated or contraindicated).

    Febuxostat is contraindicated in patients with ischaemic heart disease or congestive heart failure

  3. Co-prescription (3-months) of low-dose colchicine or low dose of an NSAID or low dose prednisolone 10mg daily.
    All ULT drugs can make an existing attack of gout worse or precipitate an acute attack.
    Therefore, continue co-prescription until at least 1 month after hyperuricaemia is corrected (usually for the first 3m with Allopurinol OR first 6m with Febuxostat) to avoid precipitating an acute attack.

  4. ULT is usually lifelong

  5. After some years of treatment, once serum uric acid target is reached and clinical 'cure' has been achieved (acute attacks have stopped and tophi have resolved), consider reducing the dose of ULT to maintain the serum uric acid level between 300-360 micromol/L.

Thresholds (target of ULT < 300 μmol/L)

The objective of urate lowering therapy in all patients is to lower serum uric acid below its physiological saturation threshold in body tissues. 

  • The EULAR recommendations advocate lowering serum urate below 360 μmol/L, which has been shown to prevent acute attacks, reduce crystal load, and shrink tophi

  • The BSR guideline recommends a more stringent initial target of below 300 μmol/L


Drug interactions which potentially increase the toxicity of colchicine

  • Amiodarone

  • Ciclosporin

  • Digoxin

  • Diltiazem

  • Fibrates

  • Antifungals (itraconazole, ketoconazole)

  • Macrolide antibiotics

  • Protease inhibitors

  • Statins

  • Verapamil


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Referral to rheumatologist

The diagnosis is uncertain.

  • Suspect septic arthritis

  • There is an underlying systemic illness.

  • Gout occurs during pregnancy or in a person under 30 years of age.

  • There are persistent symptoms despite treatment.

  • ULT is required but allopurinol and febuxostat are not tolerated, contraindicated or inadequate in lowering serum uric acid levels to target.

  • Complications are present.

  • The person is at risk of adverse effects of drug treatment.


Dr Rajesh VarmaGout