From the Journals

Study provides best support to date for using ultrasound to detect gout

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Solid evidence for usefulness with clinical suspicion of gout

The new study provides evidence that both answers and raises questions about the technical standards by which musculoskeletal ultrasound examination is used to detect gout and about what we mean when we make a clinical diagnosis of gout.

The study’s results showed that ultrasound provided excellent specificity for gout in the setting of acute calcium pyrophosphate deposition disease (CPPD), also known as pseudogout, particularly in distinguishing the deposition of monosodium urate on the surface of cartilage (double contour sign), and calcium pyrophosphate within the matrix of the cartilage (interface sign). Ultrasound’s specificity for gout apart from CPPD was particularly high when more than one feature of gout was present because one feature of gout was more often present in patients with CPPD than in non-CPPD controls, but this was not the case when two features of gout were present. However, this leaves open the possibility that some patients may concurrently have both CPPD and gout, which the study does not fully address. Apart from the level of operator experience in using ultrasound, diagnostic bias did not seem to play a role in the diagnostic utility of ultrasound because clinical appearance of scanned joints or presence of tophi did not greatly affect its sensitivity when considering that patients with tophi have more advanced disease and probably have more obvious ultrasound findings.

The study’s demonstration of ultrasound’s ability to identify tophi is important because rheumatologists consider the presence of tophi as marking the transition from hyperuricemia to gout, which often involves of inflammation and tissue damage. Many other studies have noted how people with hyperuricemia can have the double contour sign without meeting clinical criteria for gout.

It still remains important to note that, even though the test characteristics of ultrasound in the study should be generalizable, its ability to support a diagnosis of acute gout does not rule out infection in the same joint.

Eugene Y. Kissin, MD, is with the division of rheumatology at Boston University, and Michael H. Pillinger, MD, is with the division of rheumatology at New York University, New York. Their comments are derived from their editorial accompanying the study by Dr. Ogdie-Beatty and her colleagues (Arthritis Rheumatol. 2016 Oct 16. doi: 10.1002/art.39958). Dr. Kissin reported no disclosures. Dr. Pillinger reported consulting for AstraZeneca, Crealta/Horizon, and Sobi, and he has served as an investigator for a trial sponsored by Takeda.


 

FROM ARTHRITIS & RHEUMATOLOGY

Ultrasound examination of patients with at least one swollen joint or a subcutaneous nodule detected gout with a sensitivity of 76.9% and specificity of 84.3% in an international, multicenter study.

“Ultrasound is a good test for gout,” said study lead author Alexis R. Ogdie-Beatty, MD, of the University of Pennsylvania, Philadelphia. “It has high specificity, even among patients with early disease. The sensitivity was lower so it doesn’t pick up all cases of gout, although it was higher in people with a longer duration of disease.”

Dr. Alexis R. Ogdie-Beatty

Gout has a large impact on patients and the health care system in the United States. A 2013 study attributed an estimated 7 million annual ambulatory visits to gout during 2002-2008. The study estimated the cost of ambulatory care at $933 million a year, and it noted that the rate of visits per year had doubled over the time period of the study (Am J Pharm Benefits. 2013;5[2]:e46-54).

But gout remains difficult to diagnose because of the many similar types of inflammatory arthritis. A 2016 report from the Agency for Healthcare Research and Quality says proper diagnosis is a “major challenge,” especially in primary care and urgent/emergency settings.

Monosodium urate (MSU) crystal analysis via joint aspiration is considered the “gold standard” of gout diagnostic tools, but the agency report notes that it “can be technically difficult to perform and painful to the patient.”

There are other challenges. “Sometimes we see people between flares, or it’s already started to improve so there’s not enough fluid to perform an arthrocentesis,” Dr. Ogdie-Beatty said in an interview. “Additionally, while rheumatologists are generally very good at joint aspirations, many primary care physicians are not specifically trained for this. Thus, an imaging study can be helpful in these cases.”

The new study (Arthritis Rheumatol. 2016 Oct 16. doi: 10.1002/art.39959) follows up on findings from the multicenter, cross-sectional Study for Updated Gout Classification Criteria, which independently linked ultrasound analysis to diagnosis of gout with an odds ratio of 7.2 (Arthritis Care Res. 2015 Sep;67[9]:1304-15). One goal of the new study is to determine specificity and sensitivity of ultrasound exams.

The researchers examined data from the previous study, which enrolled consecutive patients in clinical practice settings across 25 countries who had at least one swollen joint or a subcutaneous nodule in whom gout was on the differential diagnosis. They underwent ultrasound examinations (most commonly of the knees, metatarsophalangeal joints, and ankles) and were deemed to have a “positive test” if at least one of three signs appeared: a “double contour” sign, tophus, or a “snowstorm” appearance. However, the study did not require a specific ultrasound scanning protocol or training.

MSU crystal examinations confirmed which of the subjects actually had gout. In total, ultrasound examinations were performed on 824 patients, of whom 416 were confirmed to have gout (mean age, 60, and 87% male), and the other 408 did not have gout (mean age, 60, and 54% male).

The researchers found that the sensitivity of the ultrasound exams was 76.9%, meaning they correctly identified patients with gout just over three-quarters of the time. Dr. Ogdie-Beatty referred to this as “moderate” sensitivity. The researchers found that the sensitivity was highest in patients who’d had disease for 2 or more years and in those who didn’t show clinical signs of tophi.

The specificity for these signs – the percentage of the time that ultrasound exams correctly identified patients without gout – was 84.3%. The positive and negative predictive values were 83.3% and 78.1%, respectively.

Dr. Ogdie-Beatty said the cost of ultrasound examinations is variable, although insurance covers it for trained providers. It’s unclear how commonly ultrasound examinations are used to detect gout, she said, but “many rheumatologists now have ultrasound as a part of their practice, and ultrasound training during fellowship has become important.”

Dr. Ogdie-Beatty reported receiving consulting fees from Novartis, and her coauthors reported various financial relationships with industry. The study was supported by various National Institutes of Health grants to several authors, as well as the American College of Rheumatology, the European League Against Rheumatism, and various arthritis-related organizations.

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