Current Concepts In Managing Chronic Gout

Scott Neville, DPM

When Patients Have Refractory Chronic Gout

Refractory chronic gout occurs in patients who have failed to normalize serum uric acid and whose signs and symptoms are not adequately controlled with xanthine oxidase inhibitors. Patients with chronic refractory gout often present to our offices with large tophi with or without ulceration. Historically, these patients have had surgical excision of the tophi. However, patients with refractory chronic gout most often present with a high comorbidity burden, adding significant risk to any planned surgical intervention. There are also the significant complications that can occur after the tophi excision itself.

   What if one could resolve tophi without surgery? A new medication, pegloticase (Krystexxa, Savient Pharmaceuticals), now offers hope for these patients with refractory chronic gout. Pegloticase catalyzes the breakdown of uric acid into allantoin, which the kidneys easily excrete. Pegloticase has the power to decrease serum uric acid to near undetectable levels.13 As I discussed above, this creates a strong gradient that acts as a powerful debulking agent. Therefore, pegloticase can significantly and quickly reduce the total body urate pool.

   Pegloticase is exciting for its potential to resolve tophi. In clinical trials, there was 100 percent resolution of at least one tophi in 45 percent of patients.13 These results can be quite rapid and dramatic. Although no medication is without risk, surgery in this patient population is not exactly risk-free either. Pegloticase offers the prospect of preventing surgery and resolving tophi pharmacologically, which is an option we have not had in our armamentarium until relatively recently.

When To Refer Patients For Gout

Everyone is going to have a different level of comfort when treating chronic gout. Some podiatrists may choose only to manage acute gouty flares while others may choose to manage the patient’s urate lowering therapy. Either choice is reasonable as long as someone on the patient’s medical team initiates urate lowering therapy in a timely manner. At the very least, it is the job of every podiatrist to obtain the proper care and consults to help prevent the next acute gouty attacks.

   No matter what your level of expertise is, having a good working relationship with a local rheumatologist will become necessary at some point. When should you consider calling on the expertise of a rheumatologist? Here are some clinical scenarios that may warrant a possible consult:

• if there is an unclear etiology of hyperuricemia;
• if there are refractory signs and symptoms of gout;
• if there is difficulty in reaching the target serum urate levels; and/or
• if there have been multiple and/or serious adverse events from urate lowering therapy.

   Dr. Neville is a Fellow of the American College of Foot and Ankle Surgeons. He is in private practice in Indianapolis.

   The author gives special thanks to Herbert Baraf, MD, for the tophi pictures in this article.


Your article states that the goal is to reduce uric acid levels quickly. Previous articles that I have read from Podiatry Management indicate that reducing the uric acid level too quick can precipitate continued gout flares. Also, is it safe to state to patients that diet plays a small role in precipitating a gout attack since your article states that exogenous factors account for only 10%?

Please advise.

The article never suggests that reducing the serum uric acid quickly is the goal. In the article, I discussed how to properly titrate allopurinol up slowly to help reduce mobilization flares. I also covered the topic of mobilization flares in the section entitled, "What You Should Know About The Urate Lowering Therapy Paradox." It says:

"It is important to educate patients that paradoxically, the initiation of urate lowering therapy can trigger acute gouty attacks. This is thought to be secondary to the rapid decrease in the serum uric acid that causes a large change in the concentration gradient. This concentration gradient causes mobilization of the urate, which is thought to increase so-called “mobilization flares.”

Therefore, one must utilize concomitant use of nonsteroidal anti-inflammatory medications when initiating urate lowering therapy. It is important to note colchicine (Colcrys, Takeda), given at 0.6 mg PO q.d. or b.i.d., is the only FDA approved medication for gout prophylaxis."

To address your second question, I think it is important to understand that the audience for this article was physicians, not patients. I do not believe it would be wise to downplay the importance of dietary modifications to your patients, but I also believe it is important that patients have a realistic expectation of what they can hope to obtain with dietary modifications alone. Patient education about dietary modifications can be effective without urate lowering therapy as long as the serum uric acid is under 7 mg/dL. If you have a serum uric acid of 7 mg/dL and you reduce the serum uric acid by 10% with dietary modification, the serum uric acid will still be a sub-therapeutic 7.3 mg/dL. I think it is extremely important that both patients and physicians understand this because in many cases, urate lowering therapy will need to be utilized in conjunction with dietary modifications.

As a podiatric surgeon and a gout sufferer, Ihave only one question. How does one ensure the serum uric acid stays below 6 mg/dl ( or 5 in UK )?

Lewis Stuttard

One of the main reasons why serum uric acid is persistently sub-therapeutic is inappropriate dosing of urate lowering therapy. For instance, in multiple studies, allopurinol is consistently under-dosed, resulting in sub-therapeutic serum uric acid levels.

If we assume that a patient is on an appropriate urate lowering therapy at the appropriate dose and that patient continues to be symptomatic, that is the definition of refractory chronic gout. Krystexxa is the only FDA-approved medication for refractory chronic gout.

I would encourage such a patient to seek out a local Krystexxa representative to find a physician in the area who is knowledgeable about Krystexxa.

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