• Clinical science
  • Clinician

Gout and hyperuricemia

Summary

Gout is a common inflammatory arthropathy characterized by painful and swollen joints resulting from precipitating uric acid crystals. Decreased renal excretion and/or increased production of uric acid leads to hyperuricemia, which is commonly asymptomatic, but also predisposes to gout. Acute gout attacks 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 synovial fluid analysis, which reveals negatively birefringent monosodium urate crystals. Acute attacks are treated with nonsteroidal anti-inflammatory drugs (e.g., naproxen, indomethacin), while management of chronic gout includes lifestyle modifications and possibly allopurinol to control hyperuricemia.

Epidemiology

  • 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.

Etiology

Hyperuricemia

Insufficient excretion or increased production of purines lead to hyperuricemia, which predisposes to gout and possibly triggers acute gout attacks.

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]

Acute gout attack

  • Triggers
    • Anything that leads to a sudden increase in uric acid, e.g., consuming a large amount of purine-rich foods or alcohol (see above)
    • Trauma, surgery
    • Diuresis
    • Dehydration

Pathophysiology

Clinical features

Asymptomatic stage

Acute gouty arthritis

  • Definition: an inflammatory arthropathy caused by urate crystal deposition within a joint
  • 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. [8]
    • Symptoms peak after 12–24 hours and regression may take days to weeks. [9]
    • The recovering joint may manifest with desquamation of the overlying skin.
  • Location

Intercritical stage

  • Asymptomatic
  • May also last up to several years

Chronic gouty arthritis

Diagnostics

Arthrocentesis

  • Indications
    • New-onset acute gout attack
    • If past suspected gout attacks were not confirmed via polarized light microscopy
  • Expected findings
    • Polarized light microscopy: needle-shaped monosodium urate crystals that are negatively birefringent (crystals appear yellow when their optical axis is oriented parallel to the polarizer and blue if their axis is perpendicular to the polarizer )
    • Synovial fluid: WBC > 2000/μL with > 50% neutrophils

Laboratory tests

Imaging

  • Ultrasound
    • "Double-contour" sign representing hyperechoic monosodium urate crystals covering hyperechoic bone contour
    • Tophus (a mixture of hyperechoic and hypoechoic structures)
  • X-ray
    • Not useful in acute gout attack, as early changes cannot be detected [9]
    • Chronic gout
      • Punched-out lytic bone lesions with spiky periosteal appositions
      • Radiopaque soft tissue
  • MRI
    • Excellent measure to detect tophi formation
    • Method of choice to detect spinal involvement
  • CT: can detect bone erosions as well as tophi [9]

Acute gouty arthritis is not always associated with elevated serum uric acid levels. It can also occur when serum uric acid is normal.

Pathology

Foreign body granuloma

  • Caused by urate crystal deposition in cutis and subcutis
  • Findings include:
    • Clusters of crystal deposits
    • Macrophages in the shape of epithelioid cells or polynuclear giant cells

Differential diagnoses

See “Differential diagnoses of inflammatory arthritis.”

Calcium pyrophosphate deposition disease (pseudogout)

To remember the main features of PSeudogout (positive birefringence, CAlcium pyrophosphate depositions, RhOMboid-shaped crystals, CHOndrocalcinosis, most often affects the knee), think of: “My PSychic is positive that I CAn find ROMance if I smear CHOcolate on my knee.”

The differential diagnoses listed here are not exhaustive.

Treatment

Acute gout attack

General measures

  • Local ice therapy may help to relieve pain. [13]
  • Rest of the affected joint to avoid recurrence

Medical therapy

Proton pump inhibitors should be given to patients being treated with both NSAIDs and glucocorticoids to avoid gastrointestinal ulcers.

Chronic gout

General measures

  • Weight loss (if applicable)
  • Reduce alcohol consumption
  • Reduce intake in red meat and seafood
  • Sufficient/high fluid intake
  • Close management of diabetes and blood pressure
  • Consuming dairy products, vitamin C, and coffee can lower levels of uric acids and therefore prevent gout. [9]

Medical therapy

  • Indications
  • General approach [18]
    • Delay initiation of urate-lowering medication until ∼ 2 weeks after an acute attack has resolved
    • Despite their therapeutic effect, urate-lowering medications may trigger or prolong an acute gout attack.
    • To prevent acute exacerbations, urate-lowering drugs should be combined with colchicine when therapy is initiated.
Medical treatment of chronic gout

First-line treatment

Xanthine oxidase inhibitor (allopurinol) [18]

Second-line treatment

Uricosuric medications (benzbromarone, probenecid, lesinurad)

Third-line treatment

Recombinant uricase (pegloticase)

Mechanism of action
  • Catalyzes the breakdown of uric acid to allantoin (due to high water-solubility)
Notable side effects

Indications

  • As an alternative to or in combination with allopurinol
Contraindications

Interaction

  • No particular drug interactions

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

During the first 2 weeks of an acute gout attack, treatment with urate-lowering drugs (e.g., allopurinol) should not be initiated or used cautiously because they can lead to urate crystal mobilization, which may worsen symptoms!

Complications

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

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last updated 11/27/2020
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