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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.

Infection

Dr. Mandell: Let’s turn to the hospitalized patient—a patient admitted to the medical service with infection. This patient is going to get fluids and drugs, and these are likely to raise or drop the serum urate level, which may precipitate a gout attack. From your perspective as an infectious disease consultant, Jim, how does the coexistence of a documented infection in the hospital—which you’re treating—factor into which agents to use or avoid when treating acute gout?

Dr. Pile: In practice, I try to avoid steroids in that situation. Theoretically, however, I’m not sure this scenario is really a contraindication to steroid use. I’m not aware of much solid data showing, for example, that patients with community-acquired pneumonia on appropriate antibiotic therapy have worse outcomes if they receive steroids than if they do not. Certainly there are a variety of serious infections for which we use steroids as a matter of course, including pneumococcal or tuberculous meningitis, tuberculous pericarditis, severe typhoid, and severe septic shock (the data for septic shock are murky, but there’s a role for at least steroid supplementation). As long as the antimicrobial therapy is appropriate, patients with serious infections are not necessarily going to do any worse with steroids.

Dr. Edwards: The biggest risk from steroids would be masking the symptoms of an unrecognized infection. If you know the infection is there and you’re treating it appropriately, I don’t think steroids are contraindicated.

Dr. Pile: A related risk is that steroids can make it more difficult to monitor the course of a known infection by blunting the overall response and bumping up the white blood cell count.

Dr. Mandell: My practice would fall in the realm of what Jim described as the theoretical course of action. If I knew what the infection was or felt comfortable in treating it, I would not shy away from systemic corticosteroids in the hospital setting, where I could monitor the patient. I think a corticosteroid may often be the safest drug to use in that setting, given the likelihood of comorbidities, at least compared with NSAIDs.

Dr. Simkin: Let’s say a patient comes in with acute knee pain and you aspirate the knee. The question arises whether you should wait for the culture results or go ahead and inject steroid while your needle is in the knee. I certainly have a much lower threshold to go ahead and inject while I’m in there, although I’d always be sure to get the culture results and revisit as needed. But if I pull out extremely inflammatory fluid during the aspiration, I’m probably not going to inject the steroid.

Dr. Edwards: And what if you actually do inject an infected joint with a corticosteroid—are you doing harm?

Dr. Simkin: I would like to think I’m not, and I may be helping.

Dr. Edwards: Yes, there are a lot of theoretical reasons why you might be helping, and there’s a small literature on steroids and infected joints that suggests you might actually slow down some bone resorptive steps and be doing various similar things.

Dr. Mandell: But in humans (a series of pediatric patients with septic arthritis30), those were systemic steroids, not intra-articular.

Dr. Edwards: In animal studies there is some amelioration of the destructive component with intra-articular steroids. The main point is that we must send off the fluid for culture when we inject steroid into a joint, and we must follow up on the cultures to make sure nothing is growing in a joint because we’re going to be calming it down. Whatever the inflammatory process is—whether infection or crystalline or rheumatoid—the patient is initially going to get better with a steroid injection. So we can’t use initial clinical improvement as the marker that we’ve done the right thing. We need to make sure the aspirate culture is negative.

Dr. Mandell: What about the use of colchicine or an IL-1 antagonist in the setting of infection?

Dr. Pile: There may be some theoretical concern, but I think low-dose colchicine would be a reasonable agent to use in the setting of infection.

Dr. Edwards: I don’t think there’s much concern since IV colchicine has been taken off the market. IV colchicine had a much more profound effect on bone marrow, and this resulted in a number of deaths from infection in immunosuppressed patients such as chemotherapy recipients. But oral colchicine in the doses we use for acute attacks and for maintenance probably doesn’t have a very profound effect on response to infectious processes or on white blood cell production (in the absence of chronic kidney disease).

Dr. Pile: Which raises the point that if the patient were on a potent inhibitor of the cytochrome P450 3A4 system, you might conceivably get into the same situation. For example, serious toxicity and even fatalities have been reported in patients taking colchicine and clarithromycin concurrently.31

Dr. Mandell: Peter, would you be comfortable giving an IL-1 antagonist to a hospitalized patient with pneumonia that’s being treated with antibiotics? Let’s say the patient has chronic kidney disease and diabetes and you’re looking for an agent to use.

Dr. Simkin: Well, I wouldn’t be comfortable, but I might feel I had to do it. If the organism were known, as you said, and the antibiotic therapy were appropriate, I might depend on that antibiotic coverage.

Dr. Sundy: Although I can envision some scenarios where I’d use the IL-1 antagonist in this situation, I’d be looking for an alternative. My concern is that people with any source of infection were excluded from clinical trials of anakinra, so we don’t have a good understanding of how it behaves in the setting of infection.

Dr. Edwards: And the fact that anakinra is not approved by the Food and Drug Administration (FDA) for treatment of acute gout should make us a bit uncomfortable.

Dr. Mandell: It’s interesting that the limited data do not show a lot of infections with IL-1 antagonist therapy other than when combined with anti–tumor necrosis factor therapy. The experience in periodic fever patients, who are on IL-1 antagonist therapy for many years, has not really shown this to be an agent predisposing to infection. I think this goes back to the point that if you document an infection and you’re treating it appropriately, some immunosuppressive or anti-inflammatory therapies may not be bad if you need to treat the attack of gout, particularly if it’s in a setting where you can monitor the patient well.

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