What Causes Gout Flares
Gout flares are caused by the inflammatory response to monosodium urate (MSU) crystals that deposit in joints and tissues when serum uric acid levels exceed the saturation threshold of 6.8 mg/dL. 1
Primary Mechanism
MSU crystal deposition triggers acute inflammation through activation of the NLRP3 inflammasome complex in resident macrophages and infiltrating neutrophils, leading to excessive IL-1β production and the characteristic rapid-onset severe pain and swelling. 2
The inflammatory cascade begins when uric acid crystals in the joint and surrounding tissue activate macrophages, which then overproduce IL-1β, resulting in the acute painful inflammatory response that defines a gout flare. 2
Underlying Cause: Chronic Hyperuricemia
Prolonged hyperuricemia (serum uric acid >6.8 mg/dL) is the fundamental prerequisite, as it leads to MSU crystal formation and accumulation in joints, cartilage, tendons, bursae, bone, and soft tissue. 1
Humans lack the enzyme uricase, which normally converts uric acid to allantoin, resulting in higher baseline uric acid levels that can become pathologic. 3
Risk Factors That Promote Hyperuricemia and Flares
The European League Against Rheumatism identifies specific risk factors that should be systematically assessed: 1
Modifiable Risk Factors
- Dietary factors: Excess alcohol consumption (particularly beer and spirits), non-diet sodas, meat, shellfish, and fructose-rich foods and beverages 1, 4
- Obesity and overweight status 1
- Medications: Diuretics, low-dose aspirin, cyclosporine, and tacrolimus 1
Non-Modifiable Risk Factors
- Male gender 1
- Chronic kidney disease with impaired uric acid excretion 1
- Associated cardiovascular diseases: Hypertension, ischemic heart disease, heart failure, diabetes, and dyslipidemia 1
- Certain ethnic groups: Taiwanese, Pacific Islander, and New Zealand Maori populations 4
Clinical Presentation Pattern
Gout flares characteristically present with rapid onset of severe pain reaching maximum intensity within 6-12 hours, accompanied by joint swelling, erythema, and tenderness. 5
Monoarticular involvement of a foot or ankle joint (especially the first metatarsophalangeal joint) is the classic initial presentation, though the disease can evolve to asymmetrical polyarticular involvement with longer disease duration. 1, 6
Disease Progression
The natural history progresses from asymptomatic hyperuricemia → asymptomatic MSU crystal deposition → acute gout flares (separated by intercritical periods) → chronic gouty arthritis with tophi formation. 1
Even during asymptomatic intercritical periods, ongoing inflammation and joint damage occur locally and systemically when serum uric acid remains elevated. 7
Critical Clinical Pitfall
Hyperuricemia alone does not cause gout flares—the diagnosis requires MSU crystal deposition with clinical manifestations, as asymptomatic hyperuricemia is common and usually does not progress to clinical gout. 1, 8
Conversely, serum uric acid levels may be normal or even low during an acute flare, so the absence of hyperuricemia does not exclude gout. 1