Review Question - QID 216401

This patient with acute onset of pain, redness, and swelling in the right big toe, as well as recent surgery, most likely has an acute gout flare. An appropriate initial pharmacotherapy would be a non-steroidal anti-inflammatory drug (NSAID) such as indomethacin.

Gout typically presents in the acute setting with monoarticular pain, swelling, and redness in a lower-extremity joint; these bouts of inflammatory arthritis are termed gout flares. Although the pathophysiology of gout flares is not fully elucidated, the deposition of monosodium urate crystals (MSU) in joints directly activates macrophages through cell-mediated interactions and triggers cytokine release from monocytes. These proinflammatory signals are amplified by neutrophils recruited to the joint, which further release inflammatory mediators such as prostaglandins, leukotriene B4, and interleukin-8. NSAIDs help reduce this proinflammatory cascade by inhibiting cyclooxygenase (COX) enzymes integral to prostaglandin formation. By preventing the amplification of inflammation in gout flares, NSAIDs are maximally effective if given at the highest recommended dose within several hours of the onset of symptoms.

Dalbeth et al. review the epidemiology, pathophysiology, diagnosis, and management of gout. The “gout flares” subsection provides a review of pharmacotherapy with NSAIDs and glucocorticoids. Box 2 discusses general principles of gout management, and Figure 8 provides a summary of the mechanism of various urate-lowering therapies. The authors also recommend the use of urate-lowering therapies such as allopurinol in the long-term management of gout.

Incorrect Answers:
Answer 1: Allopurinol is a purine base analog that inhibits xanthine oxidase, an enzyme that converts xanthine to urate. Allopurinol is often used to decrease blood urate levels to prevent recurrent gout flares. However, allopurinol has no utility in the treatment of acute gout flares, making indomethacin a better choice.

Answer 3: Pegloticase is a recombinant form of uricase, an enzyme that degrades urate to the more soluble allantoin. While pegloticase is extremely efficacious at rapidly lowering blood urate levels, it is a third-line treatment for gout prophylaxis due to the high cost and the development of resistance in many patients. Moreover, pegloticase does not have any direct benefit in the treatment of an acute gout flare, making indomethacin a better choice.

Answer 4: Prednisone is a glucocorticoid that is a rapidly acting anti-inflammatory therapy for the treatment of gout flares that may be given as an oral medication. Several randomized controls have shown oral glucocorticoids are as effective as NSAIDs and have fewer side effects. However, glucocorticoids are contraindicated in patients with a history of recent surgery due to deleterious effects on wound healing. In this patient with a recent history of open hernia repair, indomethacin is a more appropriate initial pharmacotherapy.

Answer 5: Probenecid is a uricosuric drug that decreases blood levels of urate by preventing tubular reabsorption of urate to prevent gout flares. This drug is useful in most patients with hyperuricemia, as the majority of these patients have decreased efficacy of renal uric acid excretion. However, this drug does not have any direct benefit in the treatment of gout flares, making indomethacin a better choice.

Bullet Summary:
Non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin are first-line treatments for acute gout flares.