Management of Gout

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Anticipated time to deliver the talk without cases: 30 minutes.

Anticipated time to do cases: 15 minutes.

An acute gout flare is characterized by the abrupt onset of a warm, red, excruciatingly painful, and swollen joint. Occasionally, a fever or other systemic symptoms can be present. Acute gout is considered one of the most painful joint conditions and is typically accompanied by elevated inflammatory markers and leukocytosis. Gout most commonly presents in the peripheral extremities and up to 90% of patients with gout will present with metatarsophalangeal joint involvement at some point. 73% of gout flares present in the MTP.¹ Common mimickers of gout include pseudogout, hemarthrosis, and septic arthritis. Importantly, septic arthritis is a surgical emergency as the infection can lead to rapid joint destruction.

Since both acute gout and septic arthritis can present similarly, when either condition is suspected, arthrocentesis should be performed emergently. A positive gram stain or culture is diagnostic of septic arthritis although some atypical organisms do not grow well on culture. Crystals seen on the aspirate indicate the presence of crystal arthritis, however both gout and septic arthritis can be present simultaneously. While waiting for cell culture, the synovial fluid cell count can help guide clinical concerns. In general, <2000 is non-inflammatory, 2000-75000 is inflammatory and >75,000 is high risk for septic arthritis; however, sometimes there is overlap between syndromes.² For example, patients with septic arthritis who received antibiotics prior to arthrocentesis may have lower cell counts.³ Alternatively, gouty arthritis can produce cell counts of >100,000.

Acute gout flares can be effectively treated with anti-inflammatory medications such as nonsteroidal anti-inflammatories (NSAIDs), corticosteroids (systemic or intra-articular) or colchicine.

NSAIDs should not be used in patients with a history of GI bleeding, renal disease, or ischemic cardiac disease. All full dose NSAIDs have equivalent efficacy, ease of dosing schedule is a major consideration. 

Steroids can make serum blood glucose more difficult to control in patients with diabetes and they should also be avoided in patients with concurrent infections if possible. A common dose is prednisone 40mg for 5 days.  This can be extended with or without taper for more severe or polyarticular flares. Intra-articular injections are a good option for patients with monoarticular disease who are at increased risks to systemic steroids. Typical doses include 40 mg of triamcinolone for large joints, 20 mg for medium joints, and 10 mg for small joints (or equivalent doses of alternate steroid versions).

Colchicine is another medication commonly used in acute gout flares but is only effective if initiated within the first 48 hours of symptoms. The most notable side effect of colchicine is diarrhea. Additionally, colchicine should be renally dosed in patients with kidney disease. Colchicine should be used with caution for those on statins as co-administration can increase the risk of myotoxicity.  In patients with a contraindication to NSAID, steroids, and colchicine, anakinra, an IL-1 receptor antagonist, can be used to treat polyarticular gout. ⁴ While the use of anakinra for gout is off label, it is significantly cheaper than the FDA approved canakinumab. This drug should also be avoided in the setting of active infection. Typically, when an IL-1 antagonist is being considered, a rheumatology referral should be placed.

Gout is more common in men, and the risk significantly increases with age. It is also associated with metabolic disorders such as hypertension, diabetes, and hyperlipidemia.⁵ Common precipitators of gout include diuretics (such as furosemide, Hydrochlorothiazide), Aspirin, ACE inhibitors, ARBs (except losartan), ethambutol, pyrazinamide, and nicotinic acid.  Losartan and amlodipine can provide some benefit with gout management given its uricosuric properties, so it is reasonable to consider using these agents preferentially for BP management in gout patients.⁶ The American College of Rheumatology does not recommend stopping low dose aspirin in those with an indication for use despite its risk to increase gout flares.  Additionally, patients with impaired renal function and/or conditions that lead to rapid turnover of cells such as psoriasis and leukemia have an increased risk of gout flares. The foods most likely to contribute to gout are high in purines such as red meat, seafood, alcohol (particularly beer and spirits), and fructose-rich beverages.  Higher dairy intake is associated with a lower risk of gout.⁷   Dietary modifications are recommended in addition to urate lowering therapy for chronic gout management.

Chronic treatment of gout is indicated when patients have greater than or equal to two gout flares in one year.  Per the 2020 ACR gout management guidelines, ULT is recommended in patients with one flare and in those with comorbid moderate to severe CKD (stage >/=3), serum urate concentration>9, urolithiasis, suggestive gouty erosions by x-ray, or tophi.⁸ Tophi are rock-like clusters of crystals that often occur on fingers, forearms, elbows, Achilles tendons, and the antihelixes of the ear. As radiographic findings can change management and evaluate for other gout mimics, it is important to get X-rays in the workup of gout. Starting chronic urate-lowering therapies in concurrence with acute gout treatment will not worsen or prolong the flare and therefore is advisable.⁸ Patients already on ULT should continue this throughout flares.  The most common uric acid lowering treatments include xanthene oxidase inhibitors such as allopurinol or febuxostat. Once on these medications the American College or Rheumatology recommends a treat to target approach for serum uric acid goal of <6 mg/dL.  Starting ULT without concomitant prophylaxis therapy increases the short-term risk of gout attacks until uric acid is at goal.  Therefore, addition of colchicine, low dose NSAIDs, or low dose prednisone is recommended for 3-6 months after starting ULT⁵.

All patients starting on allopurinol should be warned of the risk of allopurinol hypersensitivity reaction which can present with a cutaneous reaction, fever, peripheral eosinophilia, abnormal liver function tests, and renal failure.⁹ Individuals with a positive HLA-B*5801 allele are at a significantly higher risk of the allopurinol hypersensitivity reaction.  This allele prevalence is highest among persons of Han Chinese, Korean, and Thai ancestry (7.4%) and African Americans (3.8%).⁸  The American College of Rheumatology recommends checking HLA-B*5801 in patients with these genetic backgrounds.  If screening is positive, allopurinol should not be used.

Case 1:

Mr. P is a 72 y.o. M with a PMH of insulin dependent DM2, hypertension (controlled on an ACE inhibitor) and hyperlipidemia (on statin) who presents with one day of a hot, swollen, and painful right ankle. He denies any trauma to the area and does not endorse fever or chills.

What is the next step in diagnosis? Why is this important?

Often, we will start with an x ray of the swollen joint to look for fracture, erosions, etc. Arthrocentesis of the R ankle also needs to be part of initial management. With a new presentation of a hot, swollen joint, septic arthritis must be emergently ruled out as septic arthritis can cause rapid joint destruction.

The aspiration of his right ankle is notable for numerous intracellular negatively birefringent needle-shaped crystals. These crystals are yellow when parallel to the axis of the red plate compensator, consistent with a diagnosis of gout. Gram stain and culture are negative.

What is the best way to manage his acute flare?

Given his history of diabetes it would be best to avoid corticosteroids. The best choice would be a short course of NSAIDs. Additionally, you should review his medication list and see if there are any meds that are known to increase his risk of gout. You notice that he is on a ACE inhibitor for management of his hypertension, which is a common precipitant of gout. Therefore, you wisely switch him to losartan.

Name Mr. P’s risk factors for the development of gout.             

For this patient, his risk factors include his age, male gender, diabetes, and hyperlipidemia.

Case 2:

Mr. K is 49-year-old Han Chinese man referred to you for the management of recurrent flares of gouty arthritis. He has had three flares this year alone. PMHx is notable for chronic kidney disease and heart failure with preserved ejection fraction. On exam, he has a stone-like structure on his right elbow. His R great toe and right third MCP are hot, and tender to touch.

How would you classify Mr. K’s gout and presentation?

Tophaceous gout with acute polyarticular attack.

How would you approach management for Mr. K

Mr. K will need acute treatment for his acute gout. Given his history of renal disease and heart failure, prednisone would be a preferred first choice. Additionally, given the number of flares he has experienced, initiation of a uric acid lowering agent such as allopurinol is also warranted. Prophylaxis against flares should be continued for 3-6 months. Given his renal disease and diabetes, renally-dosed colchicine or very low dose prednisone would be a good option.

What additional lab test could you order prior to initiating allopurinol?

Given his increased risk of allopurinol hypersensitivity syndrome due to his Han Chinese background he should be tested for HLA-B5801 prior to initiating therapy.

What should Mr. K’s goal uric acid level be?

The target uric acid level for all gout patients is <6 mg/dL. 

Case 3:

Mr. J is a 60 yo M with a h/o known tophaceous gout on allopurinol and recent txt of cellulitis of his LLE who presents to clinic with 3 days of severe pain and swelling of his L ankle.

Vitals significant for temp of 38.5^℃.  Physical exam significant of warmth, erythema, and significant pain of L ankle with exquisite TTP over joint line.

What initial work up do you want to order?

• CBC- WBC 20
• CMP
• ESR, CRP
• Ankle x-ray
• Blood cultures pending
• Uric acid

*** Uric acid may be falsely low, high, or normal during acute gout flare

What would you do next?

• Arthrocentesis- synovial fluid leukocyte count 100,000, culture pending
• Polarized microscopy- negatively birefringent monosodium urate crystals

What is your next step in management?

• Consult ortho for washout/source control
• Treat with antibiotics
• Avoid steroids in the setting of acute infection, treat gout AFTER infection has been treated