Gout and hyperuricemia

Last updated: September 12, 2023

Summarytoggle arrow icon

Gout is an inflammatory crystal arthropathy caused by the precipitation and deposition of uric acid crystals in synovial fluid and tissues. Decreased renal excretion and/or increased production of uric acid leads to hyperuricemia, which is commonly asymptomatic but also predisposes to gout. Acute gout flares typically manifest with a severely painful big toe (podagra) and occur most often in men following triggers such as alcohol consumption. Diagnosis is based on clinical presentation and, ideally, by the demonstration of negatively birefringent monosodium urate (MSU) crystals on synovial fluid analysis. Acute attacks are treated with corticosteroids, NSAIDs (e.g., naproxen, indomethacin), or colchicine. The management of chronic gout includes lifestyle modifications and urate-lowering medications (e.g., allopurinol) to control hyperuricemia.

Acute calcium pyrophosphate crystal deposition (CPPD) disease, sometimes referred to as pseudogout, is another crystal arthropathy that resembles an acute gout flare and is managed similarly. It is covered in detail in a separate article.

Epidemiologytoggle arrow icon

  • Sex: : > (3:1) [1]
  • Age of onset: 2 peaks of incidence (at 30–39 years and at 60 years of age) [2]
  • Prevalence: ∼ 8 million people in the US [1]

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon


Primary hyperuricemia

  • Idiopathic extracellular supersaturation of uric acid
  • No history of comorbidities or medications that affect uric acid formation or excretion [3]

Primary hyperuricemia can be aggravated by poor dietary habits.

Secondary hyperuricemia [4]

Imagine drugs associated with gout: AS a Guy painfully walking THe NIce PYRamid LOOP trail: aspirin, thiazides, niacin, pyrazinamide, loop diuretics.

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Asymptomatic stage

Acute gouty arthritis

  • Triggers
  • Most common manifestation
    • Acute severe pain with overlying erythema, decreased range of motion, swelling, warmth
    • Possibly fever
    • Symptoms are more likely to occur at night, typically waking the patient.
    • Symptoms peak after 12–24 hours and regress over days to weeks. [10]
    • Desquamation of the skin overlying the joint may be seen during the recovery from an acute gout flare.
  • Location

Intercritical stage

  • Asymptomatic
  • May last up to several years

Chronic gouty arthritis

Diagnosticstoggle arrow icon

Identification of monosodium urate (MSU) crystals on synovial fluid analysis of the affected joint is the gold standard to diagnose gout but requires an invasive technique (i.e., arthrocentesis), trained personnel, and specialized instruments to perform the test. In patients with typical clinical features, a clinical diagnosis may be considered with/without supportive diagnostic evidence on imaging and laboratory studies.

Approach [8][12][13]

Arthrocentesis and synovial fluid analysis [8][12]

Synovial fluid analysis is the gold standard for diagnosing gout but should only be performed if polarized light microscopy is available and providers are trained in the procedure and interpretation.

Clinical diagnosis of acute gout [8][12]

There is a lack of consensus regarding strict diagnostic criteria for gout in clinical settings. [8][14][15][16]

Diagnostic rule for acute gout [17][18]
Criterion Number of points
Patient characteristics Male 2

≥ 1 of the following: hypertension, angina, MI, CHF, TIA, stroke, PVD


History of previous arthritis attack

Features of current attack Onset within 24 hours 0.5
Joint erythema 1
Affects 1stmetatarsophalangeal joint 2.5
Serum uric acid level > 5.88 mg/dL (0.35 mmol/L) 3.5


Laboratory studies

Serum uric acid levels are not always elevated in acute gouty arthritis.

Imaging [8][12][16][20]

Imaging is indicated if synovial fluid analysis is unsuccessful or cannot be performed, and the diagnosis remains uncertain. It can be used to identify supportive findings of gout but cannot rule out septic arthritis.

Ultrasound or DECT are preferred imaging modalities to detect MSU crystal deposition within affected joints.

Pathologytoggle arrow icon

Foreign body granuloma

Differential diagnosestoggle arrow icon

Treatmenttoggle arrow icon

General measures [23]

  • Lifestyle modifications may help reduce the risk of flares.
    • Limit alcohol consumption
    • Limit intake of purines (e.g., red meat and shellfish)
    • Limit high-fructose corn syrup (e.g., sugary foods, juices, and non-diet sodas)
    • Weight loss if patient is overweight
  • Identify and treat sleep apnea. [24][25]
  • Close management of comorbidities, such as diabetes and hypertension
  • Adjust current antihypertensive regimen, if feasible: losartan preferred; avoid hydrochlorothiazide [23]

Acute gout flaretoggle arrow icon

Approach [12][23][26][27][28]

If a patient is on long-term urate-lowering therapy, it should be continued during the treatment of an acute gout flare.

Avoid combining NSAIDs with systemic glucocorticoids. If prescribed together, add a proton pump inhibitor to reduce the risk of gastrointestinal ulcers.

Glucocorticoids [23][27]

  • Systemic administration
    • Oral (e.g., prednisone or prednisolone or equivalent )
      • Fixed-dose regimen: Treat for 5 days or until symptom resolution.
      • A tapered regimen may reduce the risk of a rebound flare. [30]
    • Parenteral or intramuscular (e.g., methylprednisolone ) if NPO
  • Intraarticular administration: : Consider if there are 1–2 joints that are accessible and a trained provider is available.

Glucocorticoids are preferable if there are contraindications (e.g., CKD), intolerance, or inadequate response to colchicine or NSAIDs.

NSAIDs [23][27]

  • Naproxen: or an alternative (e.g., indomethacin, ibuprofen; see “Pain management” for details)
    • Fixed-dose regimen: Treat for shortest duration necessary to resolve symptoms (often at least 3–5 days).
    • Tapered regimen for patients with:
      • Hepatic/renal impairment
      • Comorbidities
      • Severe symptoms
  • Selective COX-2 inhibitors: Consider as an alternative to naproxen in patients without contraindications.

Low-dose aspirin can decrease uric acid excretion and trigger recurrent gout flares but it should not be stopped in patients taking it for specific indications (e.g., coronary artery disease, cerebrovascular disease), regardless of the severity of gout. [23][31]

Colchicine [23][27]

Colchicine is unlikely to be effective when initiated > 24–36 hours after symptom onset. Colchicine is preferable in patients who cannot tolerate NSAIDs or systemic glucocorticoids (e.g., patients with gastrointestinal ulcers)

Monitor for myotoxicity when prescribing colchicine with statins. Reduce dose of pravastatin, atorvastatin, and simvastatin when prescribed concomitantly.

Chronic gouttoggle arrow icon

Approach [23]

Initial anti-inflammatory prophylaxis [23][26][28]

  • Indication: pre-treatment in patients planned for ULT therapy
  • Important consideration: should be initiated 1 week before starting ULT therapy
  • Options: low dose of any one of the following agents [12][23][26]
  • Treatment duration: Should be administered concomitantly with ULT for at least 3–6 months (or longer if flares continue).

Administering XOIs or uricosuric agents during an acute gout flare may worsen symptoms by mobilizing urate crystals. Anti-inflammatory prophylaxis with colchicine, NSAIDs, or glucocorticoids must be administered before initiating ULT.

Urate-lowering therapy (ULT) [23][26][27]



Important considerations

  • Timing of initiating ULT: at least one week after initiating anti-inflammatory prophylaxis (see above)
  • Titration target: serum urate < 6 mg/dL [23]
  • Treatment duration: Continue indefinitely if tolerated and in remission
  • Patient adherence: typically low ; monitoring and counseling recommended [34]


Urate-lowering therapy [23][27][35]
Drugs First-line
Xanthine oxidase inhibitors (XOIs)
Recombinant uricase
Allopurinol Febuxostat Probenecid Pegloticase
Indications [23]
  • Preferred first-line agent
  • Alternative first-line agent
  • Failure of first- and second-line medications in combination with any of the following:
    • Frequent gout attacks (≥ 2 per year)
    • Persistent subcutaneous tophi
Mechanism of action
  • Catalyzes the breakdown of uric acid to allantoin
Side effects
Important drug interactions

Test for the HLA-B*5801 allele before initiating allopurinol in black patients and patients of Southeast Asian descent.

The combination of allopurinol and azathioprine leads to increased bone marrow toxicity!

Acute management checklist for acute gout flaretoggle arrow icon

Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

Referencestoggle arrow icon

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