Top 10 Treatment Principles to Quell the Pain of Gout

Helen Paulson, MD, and Ellison L. Smith, MD

Volume 56 - Issue 9 - September 2016

ABSTRACT: Gout is a common condition for which proper treatment provides patients with great relief from pain and progressive deforming arthritis. Gout is a manifestation of hyperuricemia. Diagnosis is best made by recognizing its characteristic clinical manifestations. The natural history for most patients is gradually increasing frequency, severity, and duration of attacks. Treatment consists of treating attacks and treating the hyperuricemia; each requires different medications, along with dietary adjustments. Treatment must reduce serum uric acid levels to less than 5 or 6 mg/dL to be effective, and prophylaxis during initiation is usually indicated. Teaching patients to start a predetermined regimen for gout attacks can shorten severity and duration. Gout treatment requires patient education, and a written plan can be beneficial.

KEYWORDS: Gout, uric acid, hyperuricemia, pain management, nonsteroidal anti-inflammatory drugs, colchicine, glucocorticoids, allopurinol
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Gout is a common condition for which proper treatment provides great relief from pain, inflammation, and progressive deforming arthritis. Unfortunately, gout is commonly mismanaged. Understanding and applying the following principles and treatment strategies will help you and your patients master gout.

PATHOPHYSIOLOGY

Gout is a clinical manifestation of hyperuricemia, although only one-third of persons with hyperuricemia will clinically manifest gout. Uric acid is a normal waste product of purine metabolism that is mostly excreted by the kidneys. Hyperuricemia may occur due to decreased excretion and/or increased dietary intake of uric acid. No test is available to measure total uric acid levels in the body, although serum uric acid levels may be an approximation in some patients.

If daily uric acid clearance is insufficient, the remaining uric acid gradually accumulates over years. Eventually, the levels become high enough that the excess uric acid prompts periodic inflammatory responses known as gout attacks. Unless there is a major metabolic change, the natural history for most patients is gradually increasing frequency, severity, and duration of attacks. In up to 10% of persons with gout, overproduction of uric acid, such as that related to high cell turnover in psoriasis or neoplastic disorders, contributes to the condition.

CLINICAL MANIFESTATIONS

The clinical presentation of gout includes the following:

  • Recurrent attacks of acute inflammatory arthritis or bursitis prompted by monosodium urate crystals that gradually resolve over days or weeks.
  • Progression to chronic inflammatory arthritis and deformity due to persistent and severe hyperuricemia. This presentation can mimic rheumatoid arthritis and other deforming kinds of arthritis; however, unlike rheumatoid arthritis, gout is almost always reversible with proper prolonged uric acid–lowering treatment.
  • Collections of uric acid crystals known as tophi.
  • Uric acid nephrolithiasis.

DIAGNOSIS

While the gold standard for the diagnosis of gout is polarized microscopy of joint fluid, in practice gout is often a clinical diagnosis. Evaluate for typical recurrent episodes of acute, rapidly progressive, self-limited monarthritis, particularly involving the lower extremities, often developing overnight, with intervening periods of no disease activity. Also consider gout in patients with advanced disease in whom polyarticular and tophaceous gouty deposits cause a persistent waxing and waning polyarthritis.

Joint fluid analysis and microscopy may be indicated, depending on the clinical scenario, although the prediction calculator developed by Janssens and colleagues1 may be useful. Remember that septic arthritis is always in the differential diagnosis for gout and may coexist with gout.

Contributing factors include obesity, hypertension, older age, renal insufficiency, metabolic syndrome, alcohol intake, lead toxicity, diet rich in purines, and the use of medications, including thiazides, loop diuretics, low-dose aspirin, niacin, and calcineurin inhibitors such as cyclosporine. Gout may develop in young men but is very uncommon in premenopausal women due to the effects of estrogen. Patients on cyclosporine and other similar agents may present with particularly aggressive and resistant disease.

gout
 Crystals of uric acid, the culprit in cases of gout, viewed under polarized light microscopy. Image by cnicholsonpath/Wikimedia Commons/CC-BY-2.0.

10 TREATMENT PRINCIPLES

Treatment for gout comprises treating the inflammation and pain of an acute attack, as well as treating elevated total body uric acid levels. It is important for the health care provider and patient to understand the distinction.

1. Treat gout attacks pharmacologically.

Treat acute attacks with nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, or systemic or intra-articular glucocorticoids. Severe attacks may require multidrug treatment. Treatment should be chosen in the context of prior successful and poorly tolerated therapies, as well as other conditions such as anticoagulation, renal insufficiency, heart failure, peptic ulcer disease, and labile diabetes.

  • Any NSAID or cyclooxygenase 2 inhibitor at full dose until the attack has been resolved for 24 to 48 hours.
  • Colchicine, 1.2 mg once, then 0.6 mg 1 hour later, then 0.6 mg daily for 5 days or until the attack has resolved; instruct patients to stop the medication if diarrhea develops and discuss a lower dose with their provider (see below for cautions and dose adjustments).
  • Prednisone, 25 to 50 mg daily for 3 to 7 days, until the attack has resolved, with consideration for subsequent tapering of the medication if recurrent attacks are considered likely.
  • Intra-articular corticosteroid injection into the affected joint.

2. Develop a gout attack action plan.

Write out a gout attack action plan, such as the one accompanying this article, for your patients. Pick a treatment that you and your patient prefer for gout attacks, and ask the patient to have the treatment accessible to them. Instruct the patient to initiate therapy at the first sign of a characteristic attack and then to contact you to discuss. Prompt treatment can abort a full-blown attack.

3. Use colchicine with caution.

While colchicine is a valuable drug for the treatment of acute gout attacks and for prophylaxis against attacks, it has a narrow window of therapeutic efficacy that is further narrowed with aging, in the presence of hepatic or renal insufficiency, and in patients on cytochrome P450 3A4/​P-glycoprotein inhibitors (including cyclosporine; tacrolimus; amiodarone; quinidine; azole antifungals; verapamil; diltiazem; erythromycin, clarithromycin, and other macrolide antibiotics; and protease inhibitors). 

The dosage of colchicine should be significantly reduced by 50% to 75% and  used cautiously in these circumstances. Colchicine may be less effective if it is started more than 48 hours after an attack onset.

Colchicine toxicity can result in severe and potentially lethal bone marrow toxicities and other toxicities. Diarrhea is a sign of toxicity, so patients should be cautioned to reduce or stop treatment and discuss it with their physician if they develop diarrhea. A repeated trial on a lower dose is almost always effective. Intravenous colchicine has a much greater toxicity and is not recommended.

Combination colchicine-probenecid is much less expensive than branded colchicine, and we use this combination pill in place of branded colchicine unless patients have a probenecid allergy or other contraindication such as uric acid kidney stones. Note that while the US Food and Drug Administration has approved colchicine-probenecid for the treatment of gout, this is not an approved indication for this medication. Probenecid can cause hemolytic anemia in persons with glucose-6-phosphate dehydrogenase deficiency, and it increases drug levels of NSAIDs, acetaminophen, methotrexate, and many antibiotics, including penicillin.

4. Nondrug treatment options also are important.

Nonpharmacologic treatment to reduce the risk of recurrent gout includes weight loss and dietary adjustments. Reducing the dietary intake of purine-rich foods may reduce uric acid overload and reduce gout attacks. Purine-rich foods include red and white meat, fish, shellfish, alcohol, and fruit and soft drinks that are rich in fructose and sucrose.

Foods that can improve gout include dairy products and foods rich in vitamin C. Cherry juice has modest uric acid–lowering properties and may help with relief of gouty exacerbations.

For patients being treated for hypertension who develop gout, consider replacing diuretics with other antihypertensive treatments if possible. Losartan has modest uric acid–lowering properties.

5. Know the indications for uric acid–lowering therapy.

Urate-lowering pharmacotherapy is indicated in the following situations:

  • Polyarticular gout attacks
  • The presence of tophi clinically or on imaging studies
  • The presence of gout-related joint damage clinically or on imaging studies
  • Severe or prolonged flares as determined by the patient and health care provider
  • Frequent flares as determined by the patient and health care provider
  • Urate-associated nephrolithiasis

6. Address all the needs of patients who need urate levels lowered.

Patients who need urate-lowering treatment should be given the following:

  • Uric acid-–-lowering medication, in a dose titrated to reduce serum uric acid to below 5 or 6 mg/dL. Check serum uric acid levels after 2 to 4 weeks of medication, and adjust the dose accordingly.
  • Gout attack prophylaxis. The typical treatment is daily colchicine, a daily NSAID, or, if necessary, daily low-dose prednisone. Prophylactic therapy may be required for months or years after initiating uric acid–lowering treatment, until gout attacks cease and tophi resolve.
  • A gout attack action plan.

7. Initiate uric acid–lowering therapy when necessary, even during an acute gout attack.

Uric acid–lowering treatment should be initiated when indicated and when the opportunity presents. Uric acid–lowering therapy traditionally has not been initiated during a gout attack for fear that it may worsen the attack, although this practice may have been a disservice to many patients, given that it may reduce the likelihood that they are started on appropriate treatment regimens.

A recent study did not find an increased duration of gout symptoms in patients who were started on uric acid–lowering treatment with allopurinol with prophylactic NSAIDs or colchicine during a gout exacerbation.2 Another recent study did demonstrate a greater rate of gout attacks in the first 12 weeks when uric acid-–lowering treatment was initiated during a gout attack, although these patients did reach target serum uric acid levels more quickly than did patients in whom treatment was delayed until the gout attack had resolved.3 Uric acid-–lowering treatment should not be stopped during an attack.

8. Start with allopurinol.

Allopurinol is the first choice for nearly all patients for uric acid–lowering treatment, unless they have a history of significant allopurinol allergy. Starting at a low dose and then gradually increasing the medication reduces the risk of allergic reaction. We recommend starting with 100 mg daily in patients with normal renal function, and increasing the dosage every 2 weeks up to a goal of 300 mg, titrating thereafter to serum uric acid levels below 5 or 6 mg/dL.

Patients may require up to 900 mg of allopurinol daily, although medication adherence should be investigated in patients who require higher doses.

In elderly patients and patients with renal or hepatic insufficiency, the allopurinol starting dose should be less than 1.5 mg per mL/min of creatinine clearance and increased thereafter by 50-mg increments every 4 weeks until the serum uric acid level is less than 5 or 6 mg/dL. Allopurinol initiation has been shown to reduce mortality in patients with hyperuricemia and gout.4

Allergic reactions to allopurinol can be severe and life threatening, and they should be taken very seriously. Allopurinol hypersensitivity syndrome may present with an erythematous rash, fever, hepatitis, eosinophilia, and acute renal failure. It carries a mortality rate of 25%, and affects 0.1% of allopurinol-treated patients.

Patients of Han Chinese, Thai, or Korean descent should be tested for HLA-B*5801; if results are positive, allopurinol should be avoided due to the high risk of serious adverse reaction in these patients.

9. Know the alternative medications to allopurinol.

Febuxostat is an expensive but often beneficial uric acid-–lowering agent for patients unable to take allopurinol. Probenecid is a weak uric acid-–lowering agent that requires normal kidney function and more than once-daily dosing; therefore, it is not commonly used. Pegloticase is a uricase agent that also is used in rare circumstances.

10. Urate-lowering therapy should be  continued indefinitely for most patients.

Many patients will try stopping uric acid-–lowering therapy after years of gout remission, but the disease is likely to recur with time as total body uric acid levels once again climb.

Uric acid is dialyzed, so uric acid treatment may be discontinued in most patients on hemodialysis.

Mastering Gout

Gout is a common condition, and proper management can greatly relieve patients’ pain and progressive deforming arthritis. Understanding and applying the principles and treatment strategies discussed here will help you and your patients master gout. Note that patient adherence to gout therapy is often low. Possible contributions may include gout’s common development in young and middle-aged men who often otherwise do not seek medical care or desire medical treatment; its intermittent manifestations; and its association with alcohol use.

Relationship-building and patient education about the rationale for each treatment may improve adherence. We find that a written plan such as the one accompanying this article helps. The plan should include preventive treatment, including nonpharmacologic treatment; a gout action plan for attacks; and, if indicated, prophylaxis and daily urate-lowering treatment.

Helen Paulson, MD, is a physician at Tallahassee Memorial HealthCare Physician Partners in Quincy, Florida.

Ellison L. Smith, MD, is a physician at Asheville Arthritis and Osteoporosis Center in Asheville, North Carolina, and a clinical associate professor of medicine at the University of North Carolina at Chapel Hill School of Medicine.

References:

  1. Janssens HJEM, Fransen J, van de Lisdonk EH, van Riel PLCM, van Weel C, Janssen M. A diagnostic rule for acute gouty arthritis in primary care without joint analysis. Arch Intern Med. 2010;170(13):1120-1126.
  2. Hill EM, Sky K, Sit M, Collamer A, Higgs J. Does starting allopurinol prolong acute treated gout? A randomized clinical trial. J Clin Rheumatol. 2015;​21(3):120-125.
  3. Feng X, Li Y, Gao W. Significance of the initiation time of urate-lowering therapy in gout patients: a retrospective research. Joint Bone Spine. 2015;​82(6):428-431.
  4. Dubreuil M, Zhu Y, Zhang Y, et al. Allopurinol initiation and all-cause mortality in the general population. Ann Rheum Dis. 2015;74(7):1368-1372.