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Preventing and treating acute gout attacks across the clinical spectrum: A roundtable discussion

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Gout is the most common form of inflammatory arthritis in men, and both gout and its root cause, hyperuricemia, are increasing in prevalence in both men and women. The result is that all medical generalists and specialists undoubtedly encounter patients with acute gouty flares in the outpatient or inpatient setting.

Gout increasingly presents in patients with a number of comorbidities, including chronic kidney disease, coronary artery disease, congestive heart failure, diabetes, and hypertension. As a result, medical management of the acute attack of gout, a notably painful and debilitating condition, is growing more complicated.

I asked three of my “goutophile” rheumatology colleagues from around the country and an infectious disease specialist/hospitalist to join me earlier this year in an unscripted roundtable discussion of the management of the acute gout attack. All have extensive real-world clinical experience, and the spirit of our conversation was clinically pragmatic. We aimed to put the relevant, though limited in number, clinical trials into a very practical perspective. We focused our conversation on the diagnosis and management of the acute attack in the outpatient and inpatient settings, essentially leaving undiscussed the long-term management of hyperuricemia—the underlying cause of acute gout attacks. The roundtable and this resulting journal supplement were supported by a CME grant from URL Pharma, Inc., the manufacturer of the branded formulation of colchicine.

I believe our discussion, transcribed and published here without external editing or input, will be of value to all practitioners faced with patients enduring an acute gout attack. We’ve added references as appropriate, and I hope the result is a balanced mix of experience-based medicine from thoughtful, seasoned clinicians with quantitative supporting data provided as available from the published clinical studies. This supplement has been independently peer reviewed by a rheumatologist content expert to exclude any content that could be perceived as unjustified bias for or against any specific therapy.

Gout is a disease that has fascinated me for 30 years, and my colleagues share my sense of wonder with the dramatic nature of the acute gouty flare (and its auto-resolution). I hope our shared interest shines through here and will assist all of us in managing patients with this chronic disorder punctuated by dramatically painful attacks.

As with all issues and supplements of Cleveland Clinic Journal of Medicine, I, as the journal’s editor-in-chief, welcome your feedback and comments.

—Brian F. Mandell, MD, PhD, FACR

mandelb@ccf.org

HOW DO WE KNOW IT’S GOUT? WHEN PRESUMPTIVE DIAGNOSIS IS (AND ISN’T) ENOUGH

Brian F. Mandell, MD, PhD: In addressing acute gouty arthritis, let’s start with diagnosis. The gold standard for diagnosis of gout is synovial fluid aspiration and analysis for the presence of monosodium urate crystals. But what’s the practicality of aspiration and the need for synovial fluid analysis in a given patient at a given time? When is fluid analysis useful, and when is it absolutely necessary?

N. Lawrence Edwards, MD: It’s important to emphasize that synovial fluid analysis remains the gold standard of diagnosis. Ultrasonography of the peripheral joints is probably specific enough that it may soon be considered on par with fluid analysis for crystals, but we’re not there yet and it is not uniformly available. Less than 10% of patients who are diagnosed with gout have ever undergone synovial fluid aspiration, however, so presumptive, or “clinical,” diagnosis is very common.

A reliable presumptive diagnosis should be based on the image of a classic gout attack. The further an episode strays from a classic attack, the more presumptive the diagnosis is. So if a patient experiences the typical rapid explosion of symptoms from no pain to maximum pain over less than half a day, and if the symptoms are in the typical joints—the midfoot, the ankle, the first metatarsophalangeal joint (great toe)—that’s very consistent with a classic gout attack. Symptoms in the knee are more problematic because the two main conditions in the differential diagnosis of gout—septic arthritis and calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (pseudogout)—also commonly affect the knee.

If the patient has had acute attacks that have self-resolved or gone away with therapy over a 5- to 8-day period, that too is a profile that’s typical enough for a presumptive diagnosis of gout, especially since septic arthritis doesn’t tend to do that. Pseudogout usually is a bit slower in onset. It can look virtually identical to gout, but the affected joints often aren’t the same and the attacks tend to last for weeks rather than days, which ultimately simplifies the differential diagnosis.

The setting where synovial fluid analysis is absolutely essential is when a septic process is suspected. If there’s any nagging concern that an infection might be present, the clinician should aspirate the joint or refer the patient to someone who can. The features of a septic process may include joint swelling, rigors, and fever, but all of those can be seen in gout, so they are not distinguishing.

Dr. Mandell: John, how comfortable can you be in making the distinction between crystal-induced arthritis versus infection at the start of a given attack?

John S. Sundy, MD, PhD: Larry’s point about the features typical for gout is key, but I also consider the patient’s comorbidities and general situation. For instance, if the patient is a healthy middle-aged man with no relevant past medical history, it’s easier to feel comfortable with a presumptive diagnosis of gout. But if I’m dealing with a hospitalized patient who’s had invasive procedures and has risk factors for bacteremia, it’s imperative to get synovial fluid to rule out a septic joint. There is, of course, a continuum between these two examples. It’s important to have a construct of what typical gout is. When a case is close to that construct, it’s reasonable to work with a presumptive diagnosis; the further a case is from the construct, the more important it is to get fluid. From there it’s just a matter of overcoming the practical issues that a lot of clinicians contend with in obtaining the aspiration and fluid analysis.

Although it’s fine to think about a presumptive diagnosis and initiate treatment accordingly, it’s still incumbent upon the clinician to strive to get a firm diagnosis at some point so that the patient and physician can be 100% confident in the diagnosis.

Peter A. Simkin, MD: When we focus on the initial diagnosis we may overlook the fact that a chronically gouty joint is more susceptible to infection, so that patients who have well-established gout may still require joint aspiration to exclude acquired infection. I agree that the knee is a major site to focus on, and the olecranon bursa is another common site of infection in gouty patients.

Dr. Mandell: That’s convenient, since both of those areas are easily aspirated by rheumatologists and nonrheumatologists alike. So I’m hearing a consensus that we look at the entire clinical picture, including the historical features and the location of symptoms, to assess whether an acute attack is more likely to be gout or infection. I would add that crystal disease, especially gout, is far more common than infection, and infection is particularly unusual in the midfoot.

No objective analysis has shown that any single feature, such as leukocytosis or fever, is reliably indicative of infection versus crystal disease. Yet when we look at the entire pattern, if there isn’t significant white blood cell elevation, if there aren’t rigors, if there isn’t significant fever, and if the patient has a history of self-limited attacks, that points to a clinical diagnosis of gout that we probably can be comfortable with. That said, joint aspiration is still required if there is not a rapid response to treatment.

There are settings, as John noted, where vigilance for infection is particularly indicated, notably in hospitalized patients. Jim, as a hospitalist, you may be less apt than us rheumatologists to stick a needle into a joint. What’s your comfort level in assessing the hospitalized patient with sudden eruption of a red, swollen, painful joint?

James C. Pile, MD: I agree that the setting is very important. Let’s say I have a patient with a well-established history of gout to whom I’ve been giving aggressive diuresis for heart failure exacerbation for 2 or 3 days. If he develops a hot, swollen ankle that’s consistent with his prior episodes, I won’t typically feel obligated to stick a needle in that joint, particularly not in an ankle, for which I’d want to consult a rheumatologist in any event. If it’s a patient who underwent cardiac catheterization or other instrumentation a couple of days ago, and if this patient is febrile and has sudden eruption of a hot, swollen knee, that’s a different story. Aspiration is absolutely required in that patient, who needs to be treated as having septic arthritis until proven otherwise. But there is a lot of gray area between these two scenarios.

Dr. Mandell: Speaking of willingness to aspirate joints, there’s a concern among nonrheumatologists about putting a needle into a joint that appears to have cellulitis over it. This can stand in the way of appropriate diagnosis since the response to crystals in a joint can produce a response that looks like cellulitis. If my examination suggests joint involvement, a cellulitislike appearance does not stand in the way of aspirating the joint or bursa, which might reveal a closed-space infection.

Dr. Edwards: One population that should make us nervous any time they get an acutely swollen joint are organ transplant recipients. When these patients get gout, it’s often atypical. Not only are they usually on cyclosporine, which can cause hyperuricemia and accelerated gout, but they’re also often taking corticosteroids, which dampen the acute symptoms of gout. So whether the acute swelling is caused by gout or infection, it may not appear to be quite as profound as it actually is. Additionally, these patients may not get fever or rigors. Despite all this, they are at high risk for infection, in light of their immunosuppression. When any transplant recipient presents with acute monoarthritis, the burden of proof is on us to show that it’s not an infected joint.

Dr. Mandell: I’d add that Larry’s caveat extends to patients on any immunosuppression, including the anti–tumor necrosis factor agents, and we have seen both infection and gout in these patients.

Dr. Simkin: It’s also worth noting that joint aspiration can be therapeutic. The exquisitely painful joint often is so painful because of distention of the joint capsule. If the joint is tapped, the capsule becomes decompressed and the needle track may leave a vent through which it can remain decompressed.

Dr. Edwards: Pointing out the therapeutic benefit of joint aspiration may even be one way to get patients to allow us to put a needle into an excruciatingly painful joint. So while we advocate joint aspiration as a diagnostic procedure, often an effective approach is to explain to patients that if you tap the joint, you can treat their pain much more rapidly. Instead of having another 18 to 36 hours of pretty significant pain even on the best oral treatments, with aspiration patients might be relatively free of pain within 18 to 24 hours.

Dr. Mandell: So I’m hearing that a history of prior events consistent with attacks of crystal-induced arthritis suggests that an acute flare is likely to be another attack of crystal disease. Almost all patients with acute postoperative flares have a history of gout, though that history rarely is noted in the chart and is usually obtained later. The problem with this reliance on history is that if it’s a previously damaged joint, it may have altered microvasculature and may be more prone to infection, as Peter noted. The literature on coexistent infection in crystal disease is small, which attests to its relative infrequency, but we need to be wary of this potential for coexistence, particularly in patients at risk of infection, such as transplant recipients and those with recent infection elsewhere and bacteremia. Acute joint swelling in such patients calls for arthrocentesis.

Dr. Edwards: One last criterion for when to do a joint aspiration is when a patient with well-established gout tells you an attack is different from previous attacks. If a patient says, “This isn’t like my previous gout attacks,” that’s a red flag that usually merits joint aspiration.

Dr. Mandell: We’d be remiss if we didn’t mention the longstanding “preliminary” criteria for the diagnosis of acute gout published by the American Rheumatism Association (now the American College of Rheumatology) in 1977.1 They’ve been used for clinical research studies and also applied in principle to clinical practice. There have been a couple of recent papers examining the limitations of these criteria. How do you use these “criteria”?

Dr. Edwards: Their biggest drawback is that they’re cumbersome. They also have recently been shown to lack specificity and, to some degree, sensitivity.2

Dr. Mandell: Testing of the ACR criteria has shown that we’ve had unfounded confidence in using them in practice. As you said, their sensitivity has been reported to be 80% and their specificity even lower, at 64%.3 So even a panel of clinical indicators of gout cannot be relied on in a setting where we have concern about the possible alternative diagnosis of infection.

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