gout

gout
Name	Gout
Synonyms	Podagra (when in the big toe)
Caption	An inflamed, red joint in the big toe, a classic presentation.
Field	Rheumatology
Symptoms	Sudden severe pain, redness, swelling in joints
Complications	Tophi, Kidney stone disease, Uric acid nephropathy
Onset	Often overnight
Duration	Attacks: 3–10 days
Causes	Elevated uric acid levels in the blood
Risks	Diet high in meat or beer, Obesity, Hypertension, Kidney disease
Diagnosis	Based on symptoms, Synovial fluid analysis, Blood test
Differential	Septic arthritis, Pseudogout, Rheumatoid arthritis
Prevention	Weight loss, dietary changes, allopurinol
Treatment	NSAIDs, Colchicine, Steroids, allopurinol, probenecid
Medication	Allopurinol, Febuxostat, Probenecid
Prognosis	Good with treatment
Frequency	1–2% of the developed world at some point

gout. Gout is a common form of inflammatory arthritis characterized by recurrent attacks of a hot, swollen, and intensely painful joint. The condition is caused by persistently elevated levels of uric acid in the blood, a state known as hyperuricemia, which can lead to the formation of needle-like crystals within a joint. These attacks often begin suddenly, frequently targeting the joint at the base of the big toe, and can be triggered by factors such as dietary indiscretions, dehydration, or physical trauma. If left untreated, gout can progress to chronic joint damage and the development of visible deposits called tophi.

Signs and symptoms

The hallmark of an acute gout attack is the rapid onset of severe pain, typically reaching peak intensity within 12 to 24 hours. The affected joint, most commonly the metatarsophalangeal joint of the big toe (a condition historically termed podagra), becomes exquisitely tender, swollen, warm, and erythematous. Other joints frequently involved include the ankle, knee, wrist, and elbow. The initial attack often occurs at night and may be precipitated by events such as a heavy meal, alcohol consumption, or minor joint injury. Between attacks, patients enter an asymptomatic phase known as intercritical gout. Without adequate treatment, recurrent attacks can become more frequent and polyarticular, leading to chronic tophaceous gout where urate crystals form visible, chalky nodules (tophi) under the skin, often around the ears, olecranon bursa, or Achilles tendon.

Causes and pathophysiology

Gout is fundamentally a disorder of uric acid metabolism. Hyperuricemia arises from an imbalance between production and excretion of uric acid, the final breakdown product of purine metabolism. This can be due to increased production, as seen with high intake of purine-rich foods like red meat, organ meats, and seafood, or from conditions such as myeloproliferative disorders and Lesch-Nyhan syndrome. Decreased renal excretion is a more common cause, associated with diuretics like hydrochlorothiazide, chronic kidney disease, lead poisoning, and genetic factors. When uric acid levels exceed saturation, monosodium urate crystals precipitate in joints and surrounding tissues. These crystals are phagocytosed by neutrophils, triggering a potent inflammatory cascade involving the NLRP3 inflammasome, interleukin-1β, and other cytokines, which produces the intense local inflammation of an acute attack.

Diagnosis

A definitive diagnosis of gout is made by identifying monosodium urate crystals in synovial fluid aspirated from an affected joint during an acute attack. Under polarized light microscopy, these crystals appear as needle-shaped, negatively birefringent structures. The American College of Rheumatology and the European Alliance of Associations for Rheumatology have also established clinical diagnostic criteria for use when synovial fluid analysis is not possible. Supporting laboratory findings include elevated serum uric acid levels, though this can be normal during an acute flare. Imaging studies like ultrasonography or dual-energy CT can reveal characteristic findings such as the double contour sign or subcortical cysts. It is crucial to differentiate gout from other arthritides, particularly calcium pyrophosphate deposition disease (pseudogout) and septic arthritis.

Prevention

Long-term prevention of gout attacks focuses on maintaining serum uric acid levels below the saturation point for crystal formation. Lifestyle modifications are first-line, including weight reduction, limiting intake of high-purine foods (e.g., sweetbreads, anchovies), avoiding sugar-sweetened beverages and excessive alcohol (especially beer and spirits), and ensuring adequate hydration. Pharmacologic urate-lowering therapy is indicated for patients with frequent attacks, tophi, or evidence of urate nephropathy. The mainstay for prevention is allopurinol, a xanthine oxidase inhibitor; alternatives include febuxostat and probenecid. Initiation of these medications can paradoxically trigger acute attacks, so they are typically co-administered with prophylactic colchicine or a low-dose NSAID for several months.

Treatment

Management of gout is staged, addressing the acute attack and then long-term urate lowering. For acute flares, first-line therapies include NSAIDs (e.g., naproxen, indomethacin), colchicine, or corticosteroids (oral, intra-articular, or intravenous). Colchicine is most effective if administered within the first 12-24 hours of symptom onset. For patients with contraindications to these drugs, interleukin-1 inhibitors like anakinra or canakinumab may be used. Long-term treatment involves daily urate-lowering drugs, with the goal serum uric acid level typically below 6 mg/dL. Allopurinol is the first-choice agent, while febuxostat is an alternative. Uricosuric agents such as probenecid or lesinurad increase renal excretion of uric acid. Patient education on adherence to lifelong therapy and dietary modifications is a critical component of successful management.

Epidemiology

The prevalence and incidence of gout have risen significantly worldwide over recent decades. It is the most common form of inflammatory arthritis in men, affecting approximately 1-2% of adults in Western Europe and North America. The disease demonstrates a strong male predominance, with men being three to four times more likely to be affected than women, in whom it typically presents after menopause. Risk factors include advancing age, obesity, hypertension, metabolic syndrome, chronic kidney disease, and the use of certain medications like diuretics. Historically known as the "disease of kings" due to its association with rich diets and alcohol, its epidemiology has shifted, and it now imposes a significant burden across all socioeconomic strata. Geographic variations exist, with high rates observed in Pacific Island populations such as the Māori people of New Zealand and Native Americans.

Category:Arthritis Category:Inflammations Category:Metabolic disorders