What causes gout flares?

Causes of Gout Flares

Gout flares are triggered by multiple mechanisms including dietary factors (alcohol, high-purine foods, high-fructose corn syrup), fluctuations in serum uric acid levels (particularly during initiation of urate-lowering therapy), weight gain, certain medications, and physiologic stressors.

Primary Dietary Triggers

Alcohol Consumption

• Consuming more than 1-2 alcoholic beverages in a 24-hour period increases gout flare risk by 40% compared to periods without alcohol, with a clear dose-response relationship 1
• Beer raises serum uric acid by 0.16 mg/dL per unit consumed 1
• Heavy drinkers (≥30 units/week) continue experiencing flares despite urate-lowering therapy 1

High-Purine Foods

• A dose-response relationship exists between increasing purine intake and gout flare risk 1
• Organ meats, shellfish, and red meat are the highest-risk foods 2, 3
• However, dietary modifications alone produce only small changes in serum uric acid (approximately 10-18% reduction) 4

High-Fructose Corn Syrup

• Ingestion of 1 gram of fructose per kilogram of body weight increases serum uric acid by 1-2 mg/dL within 2 hours 1
• Artificially sweetened carbonated beverages are associated with higher serum uric acid levels 1
• Greater consumption correlates with higher risk of incident gout 1

Serum Uric Acid Fluctuations

Initiation of Urate-Lowering Therapy

• An increase in acute gout attacks occurs during early stages of allopurinol administration, even when normal or subnormal serum uric acid levels are achieved 5
• Mobilization of urates from tissue deposits causes fluctuations in serum uric acid levels, triggering flares 5
• This paradoxical flare risk occurs with all urate-lowering therapies including pegloticase, febuxostat, and allopurinol 6
• Prophylaxis with colchicine 0.5-1 mg daily is recommended during the first 6 months of urate-lowering therapy 2, 6

Fluctuation Patterns

• High fluctuation in serum uric acid during the first 9 months of treatment is related to flares over 3-month periods 7
• Fluctuation and change in serum uric acid during the first year of urate-lowering therapy are associated with flare occurrence 7
• Fluctuation due to lack of medication adherence should be avoided in clinical practice 7

Weight and Metabolic Factors

Weight Changes

• An increase in body mass index (BMI) >5% is associated with 60% higher odds of recurrent gout flare 1
• Conversely, a decrease in BMI >5% is associated with 40% lower odds of recurrent flare 1
• Mean weight loss of 5 kg results in mean serum uric acid lowering of 1.1 mg/dL 1

Medication-Induced Flares

Diuretics

• Diuretics interfere with renal tubular excretion of urate, causing hyperuricemia 3, 8
• The American College of Rheumatology conditionally recommends switching hydrochlorothiazide to an alternate antihypertensive when feasible 1

Other Medications

• Low-dose aspirin can trigger flares, though stopping it is conditionally recommended against for patients taking it for appropriate indications 1
• Cyclosporine increases hyperuricemia risk 3, 8
• Cytotoxic agents can cause rapid cell lysis and uric acid elevation 3, 8

Environmental and Physiologic Stressors

• Lead exposure, particulate matter exposure, and temperature fluctuations can trigger flares 3
• Physiologic stress has been identified as a flare trigger 3
• These factors should be considered in the appropriate clinical context 3

Clinical Pitfalls to Avoid

• Do not interpret dietary discussions as "patient-blaming"—patients frequently feel stigmatized when discussing gout 1
• Important genetic contributions exist for hyperuricemia and gout development; dietary factors serve as triggers but are not the sole cause 1
• Do not discontinue urate-lowering therapy during high-risk periods, as this can trigger flares 2
• Recognize that attacks usually become shorter and less severe after several months of therapy 5