Clinical Developments in Gout

Educational Objectives

The goal of this program is to improve management of gout. After hearing and assimilating this program, the clinician will be better able to:

1. Summarize the epidemiology of gout.
2. Develop strategies for treatment and prevention of gout.

Summary

Gout: the most common cause of inflammatory arthritis in men >40 yr of age; while the prevalence is increasing in women, most patients are men because of estrogen's protective effect until menopause; in the United States, there are ≈12 million patients with gout out of a hyperuricemic population of ≈45 million; gout is more than just hyperuricemia; recent data suggest that some people have a relative deficiency that allows monosodium urate (MSU) crystals to deposit more easily into joint tissue and soft tissues, forming tophi; the risk of developing gout correlates with serum levels of uric acid, with higher levels increasing the risk

Facets of gout: the flare can last for a few days, weeks, or months, and in patients with recurring attacks, the disease can last longer; it can be acute, subacute, or chronic; can be monoarticular, biarticular, or polyarticular; pain can be severe, throbbing, achy, dull, or mild discomfort (may be difficult to diagnose)

Presentation: patients may present with swelling on the dorsum of the hand or feet, which may resemble cellulitis; it is not infectious but crystal-induced; if the patient is diabetic or has an open foot ulcer, then gout and infection can coexist; gout is a highly inflammatory disease that can cause fever and leukocytosis; the main proinflammatory cytokines for gout are interleukin (IL)-1 and IL-6 colchicine, used for acute attacks and as a prophylactic measure, mildly suppresses IL-1; canakinumab has been approved by the US Food and Drug Administration (FDA) for the acute treatment of gout; however, it is expensive and an intravenous (IV) infusion, and should not be the first-line treatment; colchicine, corticosteroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) should be used, provided the patient's renal function is normal; serum uric acid is often normal during an acute attack because the cytokines enhance renal uric acid excretion; only 50% to 80% of patients are hyperuricemic during an acute attack; however, once the attack is resolved, patients are likely to be hyperuricemic during follow-up a few weeks later

Clinical presentation: some experts consider all gout to be tophaceous because of micro tophi deposits within the joint; joint damage may continue even in the absence of acute flares; chronic gout can mimic rheumatoid arthritis; in the early phase (up to the first decade), attacks are usually acute with pain-free periods between attacks, monoarticular, episodic, and self-limiting; this pattern continues for years with mild to moderate hyperuricemia; if not controlled or treated, the disease becomes polyarticular, without pain-free periods

Comorbidities and risk factors: data suggest that untreated hyperuricemia can lead to endothelial dysfunction and cardiovascular disease; gout is considered a component of the metabolic syndrome, with many patients having hypertension, obesity, and hyperlipidemia; ≤67% of patients with severe gout already have chronic kidney disease (CKD); high fructose corn syrup drinks induce more hyperuricemia; water, coffee, tea, and orange juice (having high vitamin C content) are good for patients with gout; diuretics, certain tuberculosis medications, nicotinic acid, and cyclosporine (used in transplant) can induce hyperuricemia

Treating acute gout attacks: colchicine is effective in treating acute gout attacks but is most effective within 24 to 48 hr of the attack; exercise caution while using colchicine in patients with CKD; other treatments include corticosteroids, NSAIDs, and IL-1 inhibitors (canakinumab)

Treating chronic gout: controlling hyperuricemia with urate-lowering therapies (eg, allopurinol) is key for preventing recurrent attacks; the therapeutic goal is to maintain serum uric acid level at ≤6.0 mg/dL; however, there is a 25% chance of precipitating an acute attack when starting allopurinol, which can be prevented by starting colchicine ≥1 wk before starting allopurinol (provided renal function is normal); if creatinine is 0.8 or 0.9 mg/dL, colchicine (0.6 mg daily) is prescribed, and allopurinol (≤100 mg) is started 1 wk later; certain patients are at risk of developing serious adverse effects to allopurinol (avoid it in patients who are HLA-B*58:01 positive)

Tips: treating hyperuricemia can prevent the development of diabetes mellitus, hypertension, obesity, and other cardiovascular diseases; some data suggest controlling hyperuricemia may also lower blood pressure, but the findings have not been replicated

Urate-lowering Agents

Probenecid: considered only mildly effective; instead, allopurinol, a purine xanthine oxidase inhibitor (XOI), is the main choice

Febuxostat (Uloric): a nonpurine XOI approved for use in patients with CKD; it can be prescribed if the creatinine clearance is ≥30 mL/min; not more effective than allopurinol but may be safer in patients with CKD; allopurinol remains the main agent, even for patients with CKD, although caution is required; even with creatinine levels of 2 or 3 mg/dL, start with 50 mg of allopurinol and gradually increase to 100 mg (sometimes 300 mg) regardless of CKD

Pegloticase: humans are usually born with uric acid oxidase deficiency; pegloticase is a synthetic uric acid oxidase (uricase); given as an IV infusion every 2 wk; patients should be screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency; uricase breaks down uric acid into allantoin, which is more water-soluble and more readily excreted by the kidney; however, the conversion process produces hydrogen peroxide, which can adversely affect patients with G6PD deficiency; pegloticase is also associated with high incidences of infusion reactions and anaphylaxis (≤50%); patients are pretreated with an immunosuppressive agent like methotrexate, azathioprine, or mycophenolate for ≈1 mo before starting pegloticase

Lesinurad: a uricosuric agent; it can induce renal dysfunction and kidney stones; allopurinol, febuxostat, or IV pegloticase are preferred; allopurinol can take years to normalize a baseline serum uric acid level of 8 or 9 mg/dL, while pegloticase can reduce this level to 1.5 or 2 mg/dL within a few hours of an infusion

Colchicine: prevents recurrent gout attacks; the recommendation is to start 7 to 10 days before allopurinol and continue until normal uricemia is achieved; can safely discontinue the colchicine if the patient becomes persistently normal uricemic; has no effect on hyperuricemia; difficult to use in patients with CKD; in a patient with a creatinine level of 2.1 to 2.5 mg/dL, dosing is 2 to 3 times weekly or every other day; for patients with severe CKD (creatinine clearance <30 mmol/L), it can be given every 2 wk or can also be used as a half dose (eg, 0.3 g)

Take-home: the American College of Physicians is more conservative than the American College of Rheumatology in starting allopurinol; if a patient has not had more than 1 or 2 attacks a year, it may be more appropriate to wait on starting a urate-lowering agent; for patients with gout who are hypertensive, agents like fenofibrate, losartan, atorvastatin (Lipitor), olmesartan, and amlodipine are recommended; reduce protein intake (especially animal protein) and add vitamin C; data on red wine are controversial; avoid alcohol; avoid diuretics (hydrochlorothiazide 12.5 mg may be fine)

Readings

Baxter B, Sanders S, Patel SA, et al. Pegloticase in uncontrolled gout: The infusion nurse perspective. J Infusion Nurs. 2023 ;46(4):p223–231. doi:10.1097/NAN.0000000000000510. View Article; Choi HK, Atkinson K, Karlson EW, et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men. New Engl J Med. 2004;350(11):p1093–1103. doi:10.1056/NEJMoa035700. View Article; Ghossan R, Aitisha Tabesh O, Fayad F, et al. Cardiovascular safety of febuxostat in patients with Gout or hyperuricemia: A systematic review of randomized controlled trials. JCR: J Clin Rheumatol. 2024;30(2):pe46–e53. doi:10.1097/RHU.0000000000002045. View Article; Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis & Rheumatism. 2008;58(1):p26–35. View Article; Mikuls TR. Gout. New Engl J Med. 2022;387(20):p1877–1887. doi:10.1056/NEJMcp2203385. View Article; Tao H, Mo Y, Liu W, et al. A review on gout: Looking back and looking ahead. Int Immunopharmacol. 2023;117:p109977. doi:10.1016/j.intimp.2023.109977. View Article; Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: The National Health and Nutrition Examination Survey 2007–2008. Arthritis & Rheumatism. 2011;63(10):p3136–3141. doi:.1002/art.30520. View Article.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Gonzalez was recorded at the 33rd Annual Essentials in Internal Medicine: Updates on Principles and Practice, held April 5-6, 2024, in Galveston, TX, and presented by the University of Texas Medical Branch. For information on upcoming CME activities from this presenter, please visit utmb.edu/pedi/education/continuing-medical-education. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

FP723902

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.