A 56-year-old man comes to the emergency department with acute onset of severe right foot pain. The pain is associated with local redness and swelling, but he has had no fever or recent trauma. The patient has never had similar symptoms. Medical history is significant for type 2 diabetes mellitus, mixed hyperlipidemia, hypertension, and coronary artery disease, for which he takes several medications. Physical examination shows a swollen, tender first metatarsophalangeal joint. Aspiration reveals a high leukocyte count, negative Gram stain, and numerous needle-shaped negatively birefringent crystals. Which of the following drugs is most likely to have precipitated this patient's condition?

Question

A 56-year-old man comes to the emergency department with acute onset of severe right foot pain.  The pain is associated with local redness and swelling, but he has had no fever or recent trauma.  The patient has never had similar symptoms.  Medical history is significant for type 2 diabetes mellitus, mixed hyperlipidemia, hypertension, and coronary artery disease, for which he takes several medications.  Physical examination shows a swollen, tender first metatarsophalangeal joint.  Aspiration reveals a high leukocyte count, negative Gram stain, and numerous needle-shaped negatively birefringent crystals.  Which of the following drugs is most likely to have precipitated this patient's condition?

Quizplus · Accepted Answer

11ec160b_3c7b_cb67_9249_2d80dd4c0213_MD0001_00 This patient has an acute inflammatory arthritis of the first metatarsophalangeal joint with needle-shaped, negatively birefringent crystals noted on joint fluid microscopy. This presentation is consistent with an acute gout flare, which occurs due to the deposition of monosodium urate crystals within joint spaces (most commonly in the lower extremities). Gout occurs in the setting of hyperuricemia, which may occur due to increased uric acid production (eg, dietary sources of purine) or reduced uric acid clearance. Most diuretics (eg, hydrochlorothiazide, furosemide) can cause hyperuricemia and trigger gout flares by causing relative volume depletion, which decreases the fractional excretion of uric acid. Other medications that can cause hyperuricemia include certain immunosuppressants (eg, cyclosporine, tacrolimus) and cytotoxic chemotherapeutic agents. In addition, medications that rapidly lower uric acid levels (eg, allopurinol) can paradoxically trigger an acute attack of gout due to mobilization of tissue urate stores (ie, dissolving crystals become fragile and more easily shed into the joint space). (Choices A and B) The lipid-lowering medication most prominently associated with gout is niacin, which decreases renal excretion of uric acid. Statins (eg, atorvastatin) can cause hepatitis and myalgias, and fibrates (eg, gemfibrozil, fenofibrate) can cause severe myopathy when given with statins; fibrates also increase the risk of cholesterol gallstones. (Choice D) Losartan has a mild uricosuric effect and can be used in hypertensive patients with gout without precipitating an acute attack of gout. (Choice E) Metformin slightly lowers uric acid, possibly due to changes in fatty acid metabolism. It is not associated with a significant risk of gout. Educational objective: Gout occurs in the setting of hyperuricemia and causes an inflammatory arthritis characterized by negative birefringent, needle-shaped crystals visible on joint fluid microscopy. Most diuretics (eg, hydrochlorothiazide, furosemide) can cause hyperuricemia and trigger gout flares by causing relative volume depletion, which decreases the fractional excretion of uric acid.

A 56-Year-Old Man Comes to the Emergency Department with Acute