- Clinical science
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 or indomethacin), while management of chronic gout includes lifestyle modifications and possibly allopurinol to control hyperuricemia.
- Sex: ♂ > ♀ (3:1)
- Age of onset: 30–60 years
- Prevalence: ∼ 8 million people in the US
- Higher incidence in African Americans
Epidemiological data refers to the US, unless otherwise specified.
- Deposition of urate crystals into joints
- Hyperuricemia predisposes to gout
- Uric acid is an end-product of purine metabolism that is renally excreted.
- Insufficient excretion or increased production of purines leads to hyperuricemia, possibly triggering a gout attack.
- May be primary or secondary.
- Idiopathic extracellular supersaturation of uric acid
- No history of comorbidities or medications that affect uric acid formation or excretion
Primary hyperuricemia is aggravated by poor dietary habits!
- Decreased uric acid excretion (most common)
- Increased uric acid production
- Combined decreased excretion and overproduction: high alcohol consumption
Uric acid has poor water solubility, even under physiological conditions. Factors that trigger urate crystal deposition include:
- ↑ Uric acid levels
- Low temperature (e.g., cool peripheral joints)
- Supersaturation of uric acid in extracellular fluid → intraarticular uric crystal precipitation (coated by IgGs) → phagocytized by polymorphonuclear cells → release of inflammatory mediators and enzymes → local joint inflammation
- Chronic effects: repeated attacks → aggregations of urate crystals and giant cells (tophi) → destruction of cartilage and bone in joints → deformities and arthritis
- Hyperuricemia with no symptoms
- May last up to 20 years or even longer
- Triggers: anything that leads to hyperuricemia (see “Etiology” above)
Arthritis: usually monoarticular during first attacks
- Acute severe pain with overlying erythema, decreased range of motion, swelling, and warmth; possible fever
- More likely to occur at night, typically waking the patient
- Symptoms peak after 12-24 hours; regression may take days to weeks.
- The recovering joint may present with desquamation of the overlying skin.
- Locations: Peripheral small joints in the lower extremities are especially affected.
- May also last up to several years
- No longer common
- Progressive joint destruction
- Tophi formation
- Renal manifestations with uric acid nephrolithiasis and
- Laboratory tests
- "Double-contour" sign representing hyperechoic monosodium urate crystals covering hyperechoic bone contour
- Tophus (a mixture of hyperechoic and hypoechoic structures)
- Excellent measure to detect tophi formation
- Method of choice to detect spinal involvement
- CT: can detect bone erosions as well as tophi
- Short description: paroxysmal joint inflammation due to calcium pyrophosphate crystal deposition (calcium pyrophosphate dihydrate)
- Sex: ♂ = ♀
- Age of onset: adults > 50 years of age
- Often asymptomatic
- Acute (pseudogout attack): monoarthritis (rarely oligoarthritis), mostly affecting the knees and other large joints (e.g., hips, wrists, and ankles)
- May become chronic (can affect multiple joints)
- Arthrocentesis should be performed, especially in acute cases.
- X-ray findings: cartilage calcification of the affected joint (chondrocalcinosis)
- Test for hypercalcemia (esp. hyperparathyroidism).
- Serum uric acid levels are normal.
- Asymptomatic cases do not require treatment unless there is an underlying condition (e.g., hyperparathyroidism).
- Symptomatic treatment (similar to gout)
- Arthroscopic lavage may also be considered
- Possible joint replacement
The differential diagnoses listed here are not exhaustive.
Acute gout attack
- NSAIDs (e.g., indomethacin, naproxen, ibuprofen)
Colchicine: inhibition of microtubule polymerization → inhibits phagocytosis of urate crystals, leukocyte activation and migration, and cell chemotaxis.
- Indications: patients who cannot tolerate ; (e.g., patients with chronic kidney disease or gastrointestinal ulcers) or oral glucocorticoids
- Prophylaxis: prevents flares of acute or recurrent gouty attacks in patients beginning uricosuric agents (e.g., probenecid) or xanthine oxidase inhibitors (e.g., allopurinol)
- Side effects: diarrhea, nephrotoxicity, and myelosuppression
- Oral glucocorticoids (e.g., prednisolone)
- Indications: particularly with single-joint involvement
- Fewer systemic side effects compared with oral corticosteroids
- Local ice therapy may help relieve pain.
- Rest the affected joint to avoid recurrence.
- Weight loss (if applicable)
- Purine-restricted diet (e.g., low-protein diet)
- Reduce alcohol consumption
- 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.
- 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.
|Second-line treatment: uricosuric medications (benzbromarone, probenecid, lesinurad pegloticase)||Recombinant uricase (rasburicase)|
|Mechanism of action|| |
|Notable side effects|
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During the first 2 weeks of an acute gout attack, treatment with urate-lowering drugs (e.g., allopurinol) should not be initiated or altered → can lead to urate crystal mobilization, which worsens the symptoms!
Uric acid nephropathy (urate nephropathy)
- Chronic tubulointerstitial nephropathy with monosodium urate crystal deposition in the stroma of the kidney → inflammatory process
- Clinical presentation
We list the most important complications. The selection is not exhaustive.