Gout | Crystal Arthropathy | Monosodium Urate

Introduction

Gout is the most common inflammatory arthritis, with a UK prevalence of ~2.5%.¹ It’s caused by monosodium urate (MSU) crystal deposition from chronic hyperuricaemia.²

It mainly affects middle-aged to older men, although the risk in women increases after menopause due to the loss of oestrogen’s uricosuric effect.³ Though flares are intermittent, gout is a chronic condition that is potentially curable with appropriate treatment.¹

Aetiology

Gout is caused by prolonged hyperuricaemia, which leads to urate supersaturation and MSU crystal deposition in joints and tissues.²

Causes of uric acid overproduction include:

• High purine intake (e.g. red meat, seafood)
• High cell turnover (e.g. psoriasis, haematological malignancies)

Causes of uric acid under-excretion include:

Hyperuricaemia does not inevitably manifest as clinical gout and may remain asymptomatic even at levels of >535 µmol/L.⁴

Risk factors

Non-modifiable

Non-modifiable risk factors for gout include:

• Male sex
• Older age (rare before 20 years old)
• Family history of gout (genetic influence on urate metabolism) ²

Modifiable

Modifiable risk factors for gout include:

• High purine intake: red meat, especially organ meats, and seafood
• Alcohol: especially beer and spirits
• Fructose-sweetened beverages (e.g. sugary soft drinks)
• Obesity: increases urate production and reduces excretion (via insulin resistance)
• Metabolic syndrome: hypertension, hyperlipidaemia, type 2 diabetes, abdominal obesity
• Thiazides and loop diuretics
• Low-dose aspirin
• Immunosuppressants: cyclosporine, tacrolimus ^{2, 5}

Clinical features

History

Typical symptoms of acute gout include:

• Severe throbbing pain in the affected joint, and extremely tender to touch
• Rapid onset, usually reaching peak intensity within 24 hours
• Swelling, warmth, and erythema over the joint
• Low-grade fever and malaise in some cases ^2-3

If untreated, the flare typically resolves over 7–14 days. Following this, patients enter an intercritical period without symptoms. Over time, recurrent flares often become more frequent and prolonged. Chronic tophaceous gout can develop after years of disease progression, with:

• Persistent joint pain and swelling
• Tophi (firm subcutaneous nodules) over fingers, toes, elbows, Achilles tendon, or ear helix
• Joint deformity, ulceration, or infection of tophi ³

On examination

Typical clinical findings in acute gout include:

• Monoarthritis, occasionally oligoarthritis
• Marked swelling and erythema
• Warmth over the joint
• Severe tenderness on palpation
• Reduced range of motion due to pain

Figure 1. Gout of the first metatarsophalangeal joint (podagra)

Typical clinical findings in chronic gout include:

• Tophi may be visible over joints and tendons
• Bony erosions and joint deformities can develop over time

Figure 2. Tophaceous gout of the right great toe and finger interphalangeal joints

Differential diagnoses

Possible differential diagnoses in suspected gout include:

• Septic arthritis: a close mimic of gout with fever and systemic symptoms; both septic arthritis and gout can co-exist
• Calcium pyrophosphate deposition disease (pseudogout): calcium pyrophosphate crystals are rhomboid and positively birefringent
• Rheumatoid arthritis: typically a chronic, symmetrical polyarthritis; chronic tophaceous gout may resemble RA
• Psoriatic arthritis: can present as monoarthritis but often includes extra-articular features, such as psoriasis
• Reactive arthritis: can present as monoarthritis but often includes extra-articular features and a recent infection
• Trauma: history of injury may suggest a fracture, haemarthrosis, or sprain
• Cellulitis: erythema, swelling, and pain are common, but the tenderness is usually diffuse rather than maximal at the joint itself, and joint movement is often less painful ⁶

Investigations

Bedside investigations

Relevant bedside investigations include:

Laboratory investigations

Relevant laboratory investigations include:

• Serum urate: >360 µmol/L supports the diagnosis of gout. Levels can be normal during an acute flare, so repeat testing 4–6 weeks after resolution is advised.
• Full blood count: white cell count often elevated but non-specific
• CRP: often elevated but non-specific
• Urea and electrolytes: to assess for renal impairment
• Glucose: risk factor monitoring
• Lipid profile: risk factor monitoring ¹

Imaging

Relevant imaging includes:

• X-ray: may show soft tissue swelling in early disease. Chronic gout is characterised by punched-out erosions with sclerotic margins and overhanging edges.
• Ultrasound: can demonstrate the double contour sign (urate deposits over cartilage), hyperechoic tophi within joints or tendons, erosions, and joint effusions.

Diagnosis

The diagnosis of gout can be made clinically without the need for synovial fluid aspiration.

Features that support the diagnosis of gout include:

• Sudden onset of severe monoarthritis, especially affecting the first metatarsophalangeal (MTP) joint
• Marked swelling, erythema, and tenderness
• Elevated serum urate (>360 µmol/L), although levels may be normal during an acute flare

Identification of monosodium urate crystals in synovial fluid or aspirated tophi confirms the diagnosis.

ACR/EULAR classification criteria (2015)

These criteria are mainly used in research but can also support diagnosis in clinical practice. The scoring system considers:

• Clinical presentation, including the pattern and time course of joint involvement
• Presence of tophi
• Serum urate concentration
• Imaging findings of urate deposition
• Identification of crystals on synovial fluid analysis ⁷

A total score of 8 points or more is highly specific for gout.

Management

Conservative management

Conservative management of gout includes:

• Lifestyle and risk factor modification: including reduction of purine-rich foods, alcohol, sugar, weight loss, and exercise
• Medication review: for identification and potential cessation of exacerbating agents
• Rest and elevation of the affected joint
• Ice packs to reduce pain and swelling ^{2-3, 5}

Medical management

Acute gout

Treatment should begin as soon as possible to shorten the duration of symptoms.

Management options involve one of the following, dependent on comorbidities, concurrent medications and patient choice:

• NSAIDs (e.g. naproxen): consider a proton pump inhibitor for gastrointestinal protection
• Colchicine: gastrointestinal side effects are common
• Oral or intra-articular corticosteroids: if NSAIDs and colchicine are unsuitable ^{2, 5}

Severe or refractory flares may require combination therapy or specialist treatments such as IL-1 inhibitors (e.g. anakinra).²

Preventing gout

Medications for preventing gout include:

• Allopurinol: typically first line, including for patients with CKD stage 2–4 or cardiovascular disease²
• Febuxostat: an alternative if allopurinol is not tolerated; used with caution in cardiovascular disease 
• Uricosurics (e.g. probenecid) or pegloticase in refractory cases ^{2-3, 6}

Ongoing urate-lowering therapy (ULT) should be continued during an acute flare, but new therapy should not be initiated until an acute episode has resolved.²

Low-dose colchicine or NSAIDs should be considered alongside ULT for the first few months to reduce the recurrence of acute gout.

Complications

Musculoskeletal

Chronic gouty arthritis often results in recurrent inflammation in the affected joints. Over time, this can lead to cartilage erosion and bony damage, resulting in deformity, persistent pain, and loss of function.⁵

Tophi can contribute to complications such as:

• Mechanical problems that limit movement or fine motor skills
• Compression of nearby nerves or tendons
• Olecranon bursitis or skin breakdown overlying nodules
• Ulceration and, in some cases, secondary infection

Renal

Although rare, monosodium urate deposits can accumulate within the kidneys, leading to chronic interstitial nephropathy. This is frequently seen alongside hypertension or chronic kidney disease.⁵

Uric acid kidney stones develop in about 10% of patients with gout, and are more likely when serum urate remains high and urine is persistently acidic. These typically present as episodes of renal colic and may contribute to progressive kidney dysfunction. Prevention includes maintaining adequate hydration and considering urine alkalinisation (e.g. bicarbonate or citrate supplements).

Cardiovascular

Gout is recognised as an independent risk factor for cardiovascular disease.⁵

Related complications include:

This association reflects both the shared underlying risk factors, such as hypertension, obesity, and chronic kidney disease, as well as the systemic inflammation caused by urate crystal deposition. Cardiovascular risks should be assessed and managed proactively.

Psychosocial

Frequent flares and chronic joint pain can affect many aspects of life. Patients often report difficulties with work and daily activities, and some develop anxiety or low mood, related to the unpredictability of symptoms.

Reviewer

Dr Patrick O’Dwyer

Adjunct Associate Clinical Professor in General Practice and Primary Care

Editor

Dr Jamie Scriven

References

1. Abhishek A, Roddy E, Doherty M. Gout – a guide for the general and acute physicians. Clinical Medicine. 2017. Available from: [LINK].
2. Dalbeth N, Gosling AL, Gaffo A, et al. Gout. The Lancet. 2021. Available from: [LINK].
3. National Institute for Health and Care Excellence (NICE). Gout: diagnosis and management. 2022. Available from: [LINK].
4. Ragab G, Elshahaly M, Bardin T. Gout: an old disease in new perspective – A review. Journal of Advanced Research. 2017. Available from: [LINK].
5. Singh JA, Reddy SG, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Current Opinion in Rheumatology. 2011. Available from: [LINK].
6. BMJ Best Practice. Gout. 2022. Available from: [LINK].
7. Neogi T, Jansen TL, Dalbeth N, et al. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Annals of the Rheumatic Diseases. 2015. Available from: [LINK].

Image references

• Figure 1. Gonzosft. Podagra. Adapted by Jbarta. Licence: [CC BY 3.0 DE].
• Figure 2. Arthritis Research UK Primary Care Centre. Tophaceous gout. Licence: [CC BY 2.0].