Gout Experts Share Insights Into a Variety of Challenging Gout Scenarios

Dr. Stamp

Traditionally, gout diagnosis has been based on clinical findings in conjunction with laboratory findings and joint aspirates, with imaging used only if needed. But imaging may be particularly helpful for evaluating atypically presenting patients. DECT and/or ultrasound can play a helpful role in initial diagnosis in patients presenting with atypical patterns, although they may not be available in all clinical settings.

“We have all been confronted with the patient who has been diagnosed with ‘refractory seronegative rheumatoid arthritis’ when, in fact, they had undiagnosed polyarticular gout,” says Dr. Helfgott. “Fortunately, we have dual-energy CT imaging that can be very helpful in confirming the presence of urate deposition in some of these challenging cases.”

Conventional, single-energy CT can demonstrate joint erosions, but it is not very specific.⁷ In contrast, the dual-source DECT scanner shows much improved contrast between urate and non-urate deposits. A meta-analysis found it had a sensitivity of 0.87 and a specificity of 0.84 (compared with a standard of crystal identification via polarized light microscopy).⁸

Ultrasound is another helpful imaging option. Among its advantages are its availability, low cost, portability and the absence of ionizing radiation and contrast material. However, it has limited ability to image deep structures, and its success may be highly dependent on the experience and expertise of the operator.⁷

Dr. FitzGerald prefers ultrasound over DECT for diagnosis of early gout. Although DECT is more specific, he notes, it is also less sensitive early in presentation. One recent study found a false negative rate of 20% in patients with their first flare who had experienced symptoms for fewer than six weeks, potentially because DECT may not be able to pick up the tiny monosodium urate deposits seen in early gout.⁹

Dr. Stamp points out that taking a detailed history to determine the characteristics of the flares is also extremely important, and any imaging works hand in hand with this. She often starts with plain X-rays as an initial, easily available investigation, which may reveal erosions consistent with gout or evidence of an alternate diagnosis. She notes that, ideally, one should also use joint aspiration to confirm the presence of uric crystals.

One treatment challenge is managing a concurrent gout flare in a patient hospitalized for other indications, such as sepsis or acute kidney insufficiency.

Managing Gout in Post-Transplant Patients

Another challenging area is the treatment of gout in patients on certain immuno­suppressants after an organ transplant. For example, some immunosuppressants often used in transplantation contexts, such as cyclosporine and tacrolimus, are thought to increase serum uric acid levels in some patients. This makes gout more of a risk in these patients, and some experience their first gout flares due to the initiation of these drugs.¹⁰

Azathioprine is even more of a concern in the context of gout. Inhibition of xanthine oxidase via allopurinol or febuxostat increases the concentration of a metabolite of azathioprine. This leads to higher concentration of the active azathioprine metabolite associated with immune suppression, but also with bone marrow suppression, which can cause potentially fatal blood dyscrasias.¹¹

Close collaboration with the transplant team to determine optimal treatment is key, as sometimes initially prescribed transplant medications can be changed. Dr. Stamp notes, “In general, for patients on azathioprine, we ask whether the patient can be changed to mycophenolate mofetil to allow the introduction of allopurinol. If it cannot, then it can be challenging, as I would avoid both allopurinol and febuxostat.”

Another approach is dose reduction. Notes Dr. Helfgott, “In the azathioprine-treated patient, I consider using allopurinol in a significantly reduced dose—perhaps a 50% reduction from the standard dose, or even less.”

Uricosurics, such as probenecid, are another option. However, they are ineffective in patients with poor renal function. One exception is benzbromarone, which is effective in those with a creatine clearance of greater than 25 ml/min.¹² “Benzbromarone is a very useful drug in this situation; however, in many places it is not freely available,” Dr. Stamp adds.

Dr. FitzGerald notes that pegloticase might be an option in this situation, especially as immunomodulators are already required to prevent transplant rejection. Dr. Helfgott also describes another approach: intermittent anti-IL-1 therapy, such as anakinra. “Although this may not lower serum urate levels, it may allow for significant control of gouty episodes without having to prescribe higher doses of steroids on a chronic basis.”

Ruth Jessen Hickman, MD, is a graduate of the Indiana University School of Medicine. She is a freelance medical and science writer living in Bloomington, Ind.

References

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