What is the likely cause of severe pain and redness in the first metatarsophalangeal joint in a 60-year-old man with a history of systemic hypertension, gout, and dyslipidemia, recently diagnosed with congestive heart failure and new-onset diabetes mellitus, and started on Lasix (furosemide), aspirin, Plavix (clopidogrel), and metformin?

Lasix (Furosemide) is the Most Likely Culprit

Lasix (furosemide), a loop diuretic, is the medication most likely responsible for precipitating this acute gout flare in this patient with a known history of gout. Loop diuretics are well-established triggers for gout attacks by decreasing uric acid excretion and elevating serum uric acid levels. 1

Mechanism and Evidence

Loop and thiazide diuretics are recognized as common and significant risk factors for gout exacerbations, with an odds ratio of 1.72. 2 The mechanism involves:

• Diuretics elevate serum uric acid by increasing net uric acid reabsorption in the proximal tubule of the kidney. 3
• This effect becomes noticeable shortly after treatment initiation and persists throughout therapy, occurring even at low doses. 3
• The elevation in serum uric acid is dose-dependent and can precipitate acute gout flares in patients with pre-existing gout. 3

Clinical Context

This patient's presentation is particularly high-risk:

• He has a known history of gout, making him susceptible to flares when serum uric acid rises. 1
• Lasix was newly initiated 5 days ago for heart failure management, and the gout flare occurred within days of starting this medication—a temporal relationship consistent with diuretic-induced hyperuricemia. 3
• The classic presentation of severe pain and redness in the first metatarsophalangeal joint strongly suggests acute gout. 1, 4

Why Not the Other Medications?

• Aspirin: While aspirin can affect uric acid levels, low-dose aspirin (typically used for cardiovascular protection) has minimal impact on gout risk at the doses used in this clinical context. 5
• Plavix (clopidogrel): This antiplatelet agent has no established association with gout precipitation. 6
• Metformin: This antidiabetic medication is not known to trigger gout attacks and does not significantly affect serum uric acid levels. 7

Guideline-Based Management Recommendation

EULAR guidelines explicitly recommend that when gout occurs in a patient receiving loop or thiazide diuretics, the diuretic should be substituted if possible. 1 Specifically:

• For hypertension management, consider switching to losartan (which has uricosuric properties) or calcium channel blockers. 1, 2
• Losartan augments uric acid excretion and thereby decreases serum uric acid levels. 3
• If diuretic therapy cannot be discontinued due to heart failure severity, the patient will require urate-lowering therapy and prophylaxis against future flares. 1

Critical Clinical Pitfall

Do not assume that because the patient "needs" diuretic therapy for heart failure, the diuretic cannot be modified. 2 Many patients can be managed with alternative heart failure regimens that minimize gout risk, and the cardiovascular benefits of ACE inhibitors or angiotensin receptor blockers (particularly losartan) may provide dual benefits. 3