Saturday, June 15, 2013

GOUT: What is this?


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Gout currently affects about 8 million people in the United States.The spectrum of disease is wide. It starts from asymptomatic hyperuricemia, when you see elevated uric acid levels but the patient does not have any symptoms. The next phase is called acute gout, when you see the classic redness and swelling of the joint. The patient is not able to walk and is in severe pain. As these acute gout flares become more common, the periods between acute flares is called the intermittent phase, when even though the patient does not have any signs or symptoms of the disease, he is still accruing uric acid. The disease progresses and ultimately becomes what we call chronic gout, when you have uric acid deposition in various joints, which results in chronic pain and disability. It can have serious manifestations, such as kidney disease and kidney stones, and we see patients in wheelchairs.




Initial Evaluation and Management
1. Serum urate level
2. Adequacy of Xanthin oxidase inhibitor dose
3. Kidney function assessement
4. Comprehensive metabolic panel
5. Comorbidity checklist
6. Patient education
The guidelines do not choose one agent versus the other. They recommend that you could use nonsteroidal anti-inflammatory drugs (NSAIDs), oral colchicine, or even steroids for the initial management of an acute attack. All the trials with these 3 classes of drugs have shown Level A evidence, which means that the 3 are equally efficacious.

If the patient were not to respond to that initial therapy, you can do step-up therapy and combination therapy, where you add colchicine along with NSAIDs or steroids along with colchicine. The issue with NSAIDs and corticosteroids together is still controversial because of the gastrointestinal toxicity. However, you would have to look at the patient’s profile.

Results of a new trial were recently published, and they show that you can treat acute gout with low doses of colchicine. Initially dose patients with colchicine 1.2 mg and follow with 0.6 mg 1 hour later.After that, you could start the patient on the prophylactic dose, which is colchicine 0.6 mg either once a day or twice a day. The trial showed that colchicines ≤2.4 mg was equal to the 4.8-mg dose that we were using, and it is less toxic and the patients were pain free.The caveat is that the earlier you start the treatment, the better off you are. The guidelines do recommend that you start the treatment within 12 hours.

The initial management per the guidelines is that you start low, so you would start allopurinol at a dose of 50 mg. Then, depending on what the urate levels are, you uptitrate the dose every 4 to 5 weeks.However, there are times when one drug is not enough. For instance, you started allopurinol, the xanthine oxidase inhibitor. You could step up the therapy once you have reached the maximum Food and Drug Administration (FDA)-approved dose and add a uricosuric agent so that you get that additional benefit. If the second agent does not help, then you have the option of using pegloticase, which has been approved by the FDA for chronic tophaceous gout.
Several options are available, but the main point that these guidelines bring is that there is a paradigm shift. You need to monitor these patients and treat to target. The target is 6 mg/dL when it comes to the serum urate level, which has been shown in multiple studies to make the patient flare free. There are times when you have to be lower. The guidelines do recommend that you treat to target, and the target should be a serum urate level <6 dl.="" mg="" p="">





references:
  1. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63:3136-3141. Abstract
  2. Terkeltaub R. Gout in 2006: the perfect storm. Bull NYU Hosp Jt Dis. 2006;64:82-86.Abstract
  3. Khanna D, Khanna PP, Fitzgerald JD, et al; American College of Rheumatology. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 2012;64:1447-1461. Abstract
  4. Terkeltaub R, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62: 1060-1068. Abstract
  5. Khanna D, Fitzgerald JD, Khanna PP, et al; American College of Rheumatology. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64:1431-1446. Abstract
  6. Allopurinol [package insert]. Greenville, NC: DSM Pharmaceuticals, Inc for San Diego, CA: Prometheus Laboratories Inc; 2003.

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