Gout is one of the crystal arthropathies that results from excess levels of uric acid leading to precipitation in joints and other tissue (i.e. urinary tract, connective tissue).
Gout is the most common inflammatory arthritis across the world.
The overall prevalence of gout is increasing, estimated at 2.49% in the UK. It is more common in the elderly and has a male predominance with a male to female ration of 4.3:1.
High uric acid levels, or hyperuricaemia, is the single most important risk factor for the development of gout.
People with normal uric levels can still develop gout, and conversely, people with high uric acid levels may never develop gout. However, risk of gout increases significantly with increasing levels or uric acid. The 5-year cumulative incidence of gout per 1000 people is 5 for uric acid levels < 420 micromol/L but 305 for uric acid level > 599 micromol/L.
Other important risk factors for the development of gout include obesity, male gender, age, renal disease and dyslipidaemia.
Gout is a disorder of purine metabolism that results in increased levels of uric acid within the body.
Uric acid is a breakdown product of purines and it may precipitant in joints, soft tissue or urinary system leading to the clinical manifestations. High uric acid levels is the single most important risk factor for the development of gout.
Uric acid is predominantly renal excreted (70%) with the remaining excreted via the gastrointestinal tract. When there is an imbalance between production and excretion of uric acid it may crystallise and deposit in soft tissue and joints.
There are three main mechanisms leading to the development of gout:
This occurs when there is increased cell turnover or lysis of cells leading to release of purines and breakdown to uric acid. The classical causes of purine overproduction include myelo- or lymphoproliferative disorders, psoriasis or use of chemotherapy agents.
There are several foods and beverages that are rich in purines and increase the risk of developing gout. These include seafood (i.e. anchovies, sardines), red meat, alcohol and fructose-rich beverages.
Uric acid is predominantly renal excreted so anything that affects the kidneys can increase the risk of developing gout. The main causes of decreased uric acid excretion include diuretics (i.e. furosemide), acute kidney injury, chronic kidney disease, ACE inhibitors or diabetes mellitus.
Gout is the result of high uric acid levels leading to supersaturation and subsequent precipitation of monosodium urate crystals in soft tissue, joints and kidneys.
Classically, monosodium urate crystals precipitate in peripheral joints (i.e. metatarsophalangeal joints) because they are less soluble at low temperatures. Urate forms needle-like crystals that can be detected on plane-polarised light. Characteristically, monosodium urate crystals are negatively birefringent on plane-polarised light.
The deposition of crystals within joints and soft-tissue may occur asymptomatically such as in chronic gout with the formation of small gouty tophi on the skin. However, during acute attacks, crystals may trigger an acute inflammatory reaction leading to acutely painful swollen joints (i.e. crystal monoarthropathy).
The classical presentation of gout is an acutely painful and swollen joint that begins abruptly, reaches intensity within 12 hours and lasts less than 2 weeks if left untreated.
Gout typically affects the first metatarsalphalangeal joint (i.e. big toe). Other common joints include the ankles, wrists, finger joints and knees. In addition, gout may affect more than one joint at a time known as polyarticular gout. However, polyarticular gout usually only presents in 10% of cases.
If hyperuricaemia is left untreated it can lead to chronic tophaeous gout, which is characterised by the development of multiple tophi (collections of urate crystals in soft tissue). These are classically located on the helix of the ear, fingers, toes, prepatellar bursa and by the olecarnon. Overtime, recurrent flares of acute gout can lead to chronic polyarticular arthritis due to recurrent damage to joints.
The major features of long-standing hyperuricaemia is recurrent flares of acute gout, renal impairment, renal stones and degenerative arthritis.
Gout is often a clinical diagnosis based on the history and examination of an acutely painful monoathropathy in a classical location (i.e. 1st MTP).
The gold-standard for the diagnosis of gout is a joint aspiration with the demonstration of needle-shaped monosodium urate crystals within the joint.
In many cases, a joint aspiration is not required because of the high clinical suspicion of gout as well as the practicality and access to joint aspirations. However, the major differential for an acutely painful joint is septic arthritis. Therefore, if there is any concern about septic arthritis a joint aspiration should always be performed.
Gout is usually a clinical diagnosis and treatment can be initiated straight away.
Investigations are usually reserved for ongoing care after the initial episode or where septic arthritis is considered, which a medical emergency.
Although not diagnostic, raised uric acid levels helps to confirm the diagnosis of gout. They should be taken 4-6 weeks following an acute attack and they are useful for monitoring response to preventative treatments.
This is the gold standard investigation for the diagnosis of gout but rarely required. A joint aspiration should always be completed if there is concern about septic arthritis or where the diagnosis is in doubt.
Joint fluid should be sent for microscopy, culture and sensitivities. Gout is suggested by the presence of needle-shaped monosodium urate crystals that are negatively bifrengent under plane-polarised light.
Plane radiographs are usually normal in acute episodes of gout. In chronic tophaeous gout or recurrent flares of gout x-rays may highlight degenerative arthropathy and boney erosions.
Gout may occur secondary to an underlying disorder such as renal disease or be associated with co-morbidities including hypertension, dyslipidaemia or obesity. It is therefore important to screen for these conditions and perform a routine set of bloods if there is concern about an underlying disorder.
The management of gout can be divided into the acute management and long-term prevention.
Several agents can be offered as first line pharmacological treatments for an acute flare of gout. The man two treatments include NSAIDs (i.e. naproxen) or colchicine. Paracetamol can be used as a adjuvant for pain relief but is not a primary treatment.
If NSAIDs or colchicine are ineffective or contraindicated then a short course of oral steroids or an intraarticular injection of steroids can be considered.
It is important to address lifestyle factors during an acute flare or gout including dietary advice, weight loss, blood pressure control, exercise and medication review.
Urate-lowering drugs can be offered to some patients to prevent the chance of recurrent flares of gout and long-term complications.
Urate-lowering agents should be offered to the following groups:
The main urate-lowering agent is allopurinol, which a xanthine-oxidase inhibitor that prevents the conversion of hypoxanthine to xanthine and xanthine to uric acid. It should generally be initiated once an acute attack has resolved (2-4 weeks post).
After initiated of allopurinol, uric acid levels should be measured every four weeks and the dose of allopurinol can be uptitrated in relation to levels. The aim to bring uric acid levels under 300 micromol/L, which is below the saturation threshold.
Other long-term prevention options include febuxostat (Xanthine oxidase inhibitor) or longer courses of colchicine.
Have comments about these notes? Leave us feedback