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

June 1, 2010|Cleveland Clinic Journal of Medicine
Brian F. Mandell, MD, PhD;N. Lawrence Edwards, MD;John S. Sundy, MD, PhD;Peter A. Simkin, MD;James C. Pile, MD, FACP, SFHM
Author and Disclosure Information

Brian F. Mandell, MD, PhD
Department of Rheumatic and Immunologic Disease, Cleveland Clinic, Cleveland, OH

N. Lawrence Edwards, MD
Division of Rheumatology and Clinical Rheumatology, University of Florida, Gainesville, FL

John S. Sundy, MD, PhD
Divisions of Rheumatology and Immunology and of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC

Peter A. Simkin, MD
Division of Rheumatology, University of Washington School of Medicine, Seattle, WA

James C. Pile, MD
Divisions of Hospital Medicine and Infectious Diseases, MetroHealth Medical Center, Cleveland, OH

Correspondence: Brian F. Mandell, MD, PhD, Center for Vasculitis Care and Research, Cleveland Clinic, 9500 Euclid Ave., NA10, Cleveland, OH 44195; mandelb@ccf.org

The authors reported the following relevant relationships with commerical interests: Dr. Mandell—consulting (one-time consultation) for URL Pharma and consulting and teaching/speaking (in a funded CME program) for Takeda Pharmaceuticals; Dr. Edwards—consulting for Takeda Pharmaceuticals and Savient Pharmaceuticals; Dr. Sundy—consulting for Alnara Pharmaceuticals, Anadys Pharmaceuticals, Ardea Biosciences, Regeneron Pharmaceuticals, and Savient Pharmaceuticals; contracted research (through Duke University Medical Center) for Ardea Biosciences, Genentech, Neopharm, Regeneron, and Savient; membership on advisory committee/review panel for Ardea Biosciences; and teaching and speaking for Takeda Pharmaceuticals; Dr. Simkin—membership on advisory committees for Novartis and URL Pharma; Dr. Pile—membership on advisory committee/review panel for Pfizer.

This article was developed from an audio transcript of a roundtable discussion convened at Cleveland Clinic on February 6, 2010. The transcript was edited by the Cleveland Clinic Journal of Medicine staff for clarity and conciseness, and was then reviewed, revised, and approved by each of the authors/panelists.

Each author/panelist received an honorarium for participating in the roundtable that formed the basis of this article (Dr. Mandell’s honorarium was donated to the Cleveland Clinic Internal Medicine Residency Research and Education Fund). The honoraria were paid by the Cleveland Clinic Journal of Medicine from the educational grant from URL Pharma, Inc. (Mutual Pharmaceutical Company) underwriting the supplement in which this article appears. URL Pharma had no input on the content of the roundtable or this article.

CAN TRIALS OF SPECIFIC THERAPIES OFFER DIAGNOSTIC UTILITY?

Dr. Mandell: What about the response to anti-inflammatory therapy? Can we use the specificity of response to a drug like colchicine to determine whether an attack is more or less likely to be attributable to crystal disease?

Dr. Simkin: It’s certainly helpful, but entities other than crystal disease can respond to anti-inflammatory drugs, of course. For instance, some people with paraneoplastic problems will have acute arthritis that goes away with anti-inflammatory therapy. So I think it’s more a matter of how fast and complete the response is rather than whether there is a response.

Dr. Mandell: Consider the cases you’ve seen that ultimately turned out to be septic arthritis. What was the initial response in those cases to either nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or corticosteroids, and what conclusions can you draw from those cases?

Dr. Sundy: In my experience, signs and symptoms are often more lingering in these infectious cases. I think it’s fair to generalize that the response is not as rapid as with a typical gout flare. This underscores the importance of follow-up. If a patient presents to the emergency room and is treated and released, the critical question is how careful the follow-up is going to be at 24, 48, and 72 hours to see if improvement and resolution are occurring as expected. If you’re going to proceed on the basis of a presumptive diagnosis, there must be planned and frequent follow-up.

Dr. Edwards: I don’t think anyone thinks that a patient with an acute septic joint is going to get much improvement at all from oral colchicine or much more than a little fever reduction from NSAIDs without parenteral antibiotics. That joint is going to progress toward destruction within days. So John’s point is crucial that any time you make a presumptive diagnosis of gout, it’s incumbent on you to make sure that the pattern thereafter is one of resolution over time—not worsening—on the medications you use.

Dr. Pile: Even with corticosteroids, which are probably most likely to mask the clinical picture, in most cases I think it’s still fairly easy to sort things out based on response in the first 24 to 48 hours after initiating therapy. I don’t think patients with bacterial septic arthritis are going to remain better on corticosteroids.

Dr. Mandell: The time frame is crucial. Therapy for acute arthritis is ideally started fast, and patients frequently will be treated initially with an anti-inflammatory—in the community, probably more often with an NSAID than with colchicine or a steroid. Even if they actually have a septic joint, they may initially get a bit better on the anti-inflammatory, perhaps from the analgesic or antipyretic effects, but the benefit will clearly plateau and the attack will worsen again. So the period for peak vigilance is probably 1 to 2 days after therapy is started; if improvement is not maintained in this period, you should be circumspect regarding diagnosis of crystal disease and you must aspirate, or reaspirate, the joint.

Let’s explore specificity a bit further. Diagnostic specificity has historically been attributed to colchicine. People have even suggested that a diagnostic colchicine trial can be useful. How does that jibe with your experience with response to colchicine therapy in patients with entities other than gout?

Dr. Edwards: The main disease in the differential diagnosis of gout other than a septic process is pseudogout, or CPPD arthropathy, and patients with pseudogout may also respond to colchicine.

Dr. Simkin: Another entity that reportedly responds to colchicine is sarcoid, particularly sarcoid of the ankle.

Dr. Edwards: In fact, colchicine has been tried for treating the acute inflammatory symptoms of many of the diseases we see as rheumatologists. Some people swear by it, while others believe it doesn’t do much for these conditions. In any case, I don’t think its specificity for gout is very strong, and we have no basis to say that response to colchicine should serve as a diagnostic test.

Dr. Mandell: I agree, and the literature over the past few years on colchicine for treatment of acute and chronic pericarditis further argues against specificity of this drug for crystal-induced inflammation.

SERUM URATE LEVEL IS UNRELIABLE FOR DIAGNOSIS

Dr. Edwards: While we’re discussing diagnosis, nothing’s been said about serum urate levels, which I think many primary care physicians rely on heavily in the diagnosis of gout. We need to underscore that a lot of people who are hyperuricemic will never develop gout. At the same time, there’s also the phenomenon during an acute attack in which an acute uricosuria accompanies the initial inflammation, causing serum urate values to fall from what would otherwise be a high baseline to a level that looks normal. These declines may be between about 1.5 to 2.5 mg/dL, so that a patient presenting to the emergency room with a serum urate of, say, 7 mg/dL might actually have a baseline chronic level of 9 mg/dL.

Relying too heavily on serum urate levels can be misleading in either direction: someone with joint pain with serum urate elevation may be diagnosed with gout inappropriately, whereas someone who comes in with a gouty attack who has a serum urate level in the normal range may be thought not to have the disease.

Dr. Mandell: The fact that urate level didn’t come up in a conversation among rheumatologists with an interest in gout testifies that none of us uses serum urate in the diagnosis of acute arthritis. Your point is well taken, though, that serum urate is used for this purpose in the community but shouldn’t be, especially not in an acute setting.

Dr. Simkin: Indeed, I’ve seen a serum urate of 3.7 mg/dL during an acute, crystal-confirmed gout attack in a patient who was not on urate-lowering therapy.

Dr. Mandell: There’s also the issue that laboratory-defined normal levels of serum urate are not the same as biologically “normal” levels in the context of urate deposition. Levels that are in the normal range in the laboratory clearly can be above the saturation point of urate in physiologic tissues, which is about 6.7 mg/dL.

Dr. Simkin: Plus, many labs report their normal range as being up to 8 mg/dL, yet most gouty arthritis in the community probably occurs in patients with urate levels below 8 mg/dL, and this misstatement of normality certainly deserves attention.

Dr. Sundy: The issue of serum urate further underscores the importance of looking at gout as a longitudinal condition and not just as an acute episodic one. We would never treat and release a patient who came in with a severe hypertensive episode without insisting that further follow-up was indicated for the hypertension. Similarly, for a person who presents in the emergency room with gout there should be a longer-term strategy to make sure the patient understands the importance of followup to address the underlying hyperuricemia.

Dr. Mandell: Yes, there is a challenge with the system of care; the providers faced with the acute attack are not the ones who will ultimately be treating the disease and its associated comorbidities.

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