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Diagnosis, Assessment Tools and the Management of Gout

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MEDPOINT - 69th Annual Meeting of the Canadian Rheumatology Association (CRA)

Whistler, BC / February 26-March 1, 2014

Whistler, BC - Gout may be perceived as an ailment or minor illness, but it can cause as much disability as rheumatoid or psoriatic arthritis, and thus deserves urgent and expert attention. New imaging and therapeutic options are emerging in the management of gout. Though uncommon, gout and rheumatoid arthritis (RA) can coexist and because each disease requires a different therapeutic approach, it’s important to rule out gout in RA patients and vice versa. Regardless of the scale used to assess treatment efficacy, clinical tools tend to be inherently flawed. There is often considerable disagreement as to the degree of disease activity, and quality of life endpoints rated by current scales, are often not meaningful to patients and need to encompass personal values as well.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

In his workshop on managing gout in patients with complex conditions, Dr. Greg Choy, Assistant Professor of Medicine, University of Toronto, reminded delegates that they need to distinguish between acute and chronic gout as different stages of the disease are treated differently. Acute gout is characterized by red, swollen, warm joints that can be extremely painful, as Dr. Choy noted.

“Intercritical” gout describes the interlude between acute gout attacks. However, the absence of acute symptoms does not mean disease resolution, as uric acid crystals will continue to accumulate in joints if hyperuricemia is ongoing. Left undiagnosed or unchecked, patients eventually develop chronic gout with persistent symptoms and progressive disability. A definitive diagnosis of gout requires microscopic identification of monosodium urate crystals, according to Roddy et al.  (BMJ 2013;347:5648).

Until recently, there appeared to be nothing new in the management of gout, which may be why the disease still is not given the priority it deserves, suggested Dr. Choy. Now, new therapies are emerging that have and will continue to expand treatment options for gout, and physicians need to be aware of them to better manage the disease. Using an algorithm mapped out by the American College of Rheumatology (Arthritis Care & Research 2012;64:1431-46 and 1447-61), Dr. Choy noted that treatment of an acute attack should be initiated within 24 hours of symptom onset.

Acute Gout

First-line agents recommended in the treatment of acute gout include nonsteroidal anti-inflammatory drugs (NSAIDs), oral colchicine or systemic or intra-articular corticosteroids, the latter only if gout involves 1 or 2 large joints. Established urate-lowering treatments should also be continued without interruption during the acute attack. Anti-inflammatory prophylaxis is also recommended for all gout patients when urate-lowering therapy is initiated and should be continued if there is any evidence of continuing disease activity, or if target serum urate levels fail to fall to <6 mg/dL (360 µmol/L).

“If possible, I try to use the same agent for anti-inflammatory prophylaxis as I use for acute gout so if you choose an NSAID, for example, start patients off at a higher dose and lower the dose for prophylaxis,” Dr. Choy said. Many gout patients have important comorbidities, he added, especially chronic kidney disease (CKD) which predisposes patients to gout. If oral colchicine is used for prophylaxis, the dose needs to be adjusted in patients with CKD and the potential for multiple drug interactions needs to be kept in mind.

Managing Chronic Gout

Xanthin oxidase inhibitors (XOIs) are recommended as first-line agents. Allopurinol has been available for some time and febuxostat, the latest addition, is indicated to lower uric acid levels in patients with gout. As Dr. Choy cautioned, the initial dose of allopurinol should not exceed 100 mg/day and only half that dose should be used, at least initially, in patients with CKD stage 4 or higher. Allopurinol should also be titrated up slowly, he added, although following slow titration, allopurinol may be given in maintenance doses exceeding 300 mg/day, even in CKD patients.

Screening patients for the HLA-B*5801 allele which confers a high risk for severe hypersensitivity reactions can be done, but in his experience most patients do not get screened because of cost. Febuxostat is easier to administer, being a once-daily medication, while allopurinol may have to be taken up to 4 times a day. The cost of the newer agent also needs to be taken into consideration. “We know people can take allopurinol for a long time because it’s been around for 40 years,” Dr. Choy said, “but febuxostat costs more so I give patients a choice between allopurinol and febuxostat because both drugs are recommended as first-line.”

Probenecid may also be considered as an alternative first-line agent in chronic gout but it has the potential to interact with many commonly used medications and most physicians avoid it because of this. Dr. Choy also modifies concurrent medications to tip the balance in favour of lower uric acid levels. For example, if patients need antihypertensive therapy, he’ll favour losartan  over other agents as it lowers uric acid by 10 to 20% (Cardiovasc Diabetol 2013 Nov 4;12(1):159). For the same reason, he’ll also replace a statin with gemfibrozil.

Patients also need to be reminded to take care to modify their diet (beer is the worst offender) to keep uric acid levels as low as possible, added Dr. Choy.

RA and Gout

As pointed out by Dr. Lilia Olaru, Fellow, University of Alberta, Edmonton and colleagues (Abstract 41), it has long been thought that rheumatoid arthritis (RA) and gout do not exist in the same patient. Intrigued by reports that this may not be true, the Edmonton group searched the University of Alberta’s database from which 1985 patients with RA and 1977 patients with gout were reviewed. Out of this cohort, they identified 10 patients with both RA and gout who fulfilled existing criteria for both diseases. The mean age of onset of RA was 54 years while the mean age of onset of gout was 65.3 years. “Most patients developed RA first,” Dr. Olaru noted.

However, 3 patients—all males—developed gout first. It’s generally accepted that females do not develop gout until after menopause, which was the case in this cohort. Dr. Olaru also noted that given the disease duration in these patients, radiological progression appeared to be less severe from what might be expected with classic RA, with gout findings tending to be focused in joints affected by both diseases.

They also noted that patients may develop either RA or gout in different joints—“so they may have more RA in the hands and gout in the feet or the other way around,” Dr. Olaru said. “Obviously the treatment of these 2 diseases is very different so it’s important that physicians recognize that these 2 conditions can coexist,” she continued. While aspiration is required to make a definitive diagnosis, Edmonton investigators are in the process of evaluating their “gout protocol”, using dual energy CT that can detect uric acid crystals non-invasively.

“It’s still not totally validated, but I think this protocol is very promising as it would be a non-painful way to detect gout,” Dr. Olaru said.

Flawed Assessment Tools

Rheumatologists typically rely on a variety of scales to judge the effectiveness of RA therapy. But as argued by Dr. Brian Feldman, Professor and Division Head, Hospital for Sick Children, Toronto, assessment tools used in rheumatology today are inherently flawed and do not necessarily measure parameters that matter most to patients. One example of “assessment tool discordance” came from his own centre where 4 experts in pediatric rheumatology examined the same 14 patients for standard swollen joint counts (SJC) among other measures of RA activity.

“The 4 of us agreed less than half the time on which joints were swollen in these 14 patients,” Dr. Feldman reported. “There are simply problems with our measurements.” A recent $7 million, National Institutes of Health-funded trial in refractory adult and pediatric myositis (Arthritis Rheum 2013;65:314-24) found there was no difference in the time to reach the trial’s definition of improvement between the treatment strategies compared, but when Dr. Feldman and colleagues changed the definition of improvement, they could tease out differences between the two trial arms.

“We need to learn how to value change better,” he added. For example, when a group of children with chronic illness were asked what aspects of life were important to them, having friends, being happy and getting along with parents were rated far ahead in terms of importance to these children than any need to better manage their physical disabilities.

“Quality of life is not just health-related, it’s all aspects of life,” Dr. Feldman reminded delegates.  “And personal values always come into play.”

Summary

Gout is the most common form of inflammatory arthritis and acute gout is one of its most painful presentations. Undiagnosed and inadequately treated, continuing crystal deposition can cause irreversible joint damage. Traditional uptake of non-pharmacological and pharmacological treatment for both acute and chronic gout has been poor, as much depends on patient education and commitment. Therapies that are more easily administered, better tolerated, and with fewer concurrent drug interactions, may help make the management of gout more successful. In diagnosis, gout needs to be ruled out in RA patients and RA in gout patients to ensure patients are appropriately treated. The success of therapy may be driven more by patient perception than is generally acknowledged, and interpreting clinical measures of efficacy needs to be improved. 

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