Sonography Protocols Inconsistent for Asymptomatic Hyperuricemia Detection

Credit: Adobe Stock/ YURII MASLAK

A new study reveals the inconsistency in current sonographic protocols for detecting uric acid crystal deposits in individuals with asymptomatic hyperuricemia and the importance of establishing a standardized method.¹

“We found that the rate of participants who met the different definitions varied drastically, from 23.4% to 87.0%,” wrote investigators, led by María-Luisa Peral-Garrido, from Vinalopó University Hospital, in Spain.

The detection of preclinical monosodium urate crystal deposition in people with asymptomatic hyperuricemia was a significant breakthrough in gout care over the past decades. Although discovered > 40 years ago, no universally defined sonographic protocol exists for assessing urate crystal deposits in asymptomatic hyperuricemia or how different sonographic protocols impact deposit rates.

A physiochemical definition of hyperuricemia, related to urate crystal deposition, is widely preferred due to the non-normal distribution of serum urate concentrations in many populations.² Here hyperuricemia is described as the solubility threshold of urate in body fluids where urate concentrations exceed 7 mg/dL. Other definitions relate to non-crystal deposition associations, such as the high prevalence of urate values exceeding saturation and the putative effects of increased serum urate levels on cardiovascular and other disorders.

Investigators sought to see how using different sonographic definitions and schemes varied the prevalence of crystal deposits in people with asymptomatic hyperuricemia.¹ They conducted a comparative study of 77 participants with asymptomatic hyperuricemia.

Patients with asymptomatic hyperuricemia (serum urate ≥ 7 mg/dL) underwent musculoskeletal ultrasound at 10 different locations on their bodies. The ultrasound aimed to identify and assess specific elementary lesions associated with gout, as defined by the Outcome Measures in Rheumatology (OMERACT) group. These lesions included double contour, tophi, and aggregates.

Investigators used different definitions for asymptomatic hyperuricemia with uric acid crystal deposits. Definitions varied by deposits (any deposits or only double contour and tophi), gradation (any grade or only grade 2-3 deposits), location (10 locations; 4-joint scheme including knees and the first metatarsophalangeal joints (1MTPS); > 1 location with deposits), or pre-defined definitions (double contour sign in femoral condyles/ 1 MTP/ tophi in 1 MTP).

Participants had a median of 1 location (IQR, 0 – 2) with tophi, 1 location (IQR, 1 – 2) with aggregates, and 0 locations (IQR, 0 – 1) with the double contour sign. The deposition rate ranged from 23.4% in > 1 location with grade 2 -3 double contour or tophi to 87% in any deposit in all 10 locations. Erosions were found in 19.5% and 28.4% of participants, respectively, assessed by a positive power Doppler signal.

Investigators found the positive power Doppler signal was more pronounced when criteria required grade 2 – 3 lesions or lesions in ≥ 1 location. However, erosions, as well as clinical and laboratory variables, were similar among protocols.

“According to these data, [power Doppler] signal could be used to tag [monosodium urate] crystal deposition in [asymptomatic hyperuricemia] in a more certain way,” investigators wrote. “It might also indicate more severe crystal deposition, with a higher risk of developing the first flare, erosive damage, or even cardiovascular events, making these patients potential candidates for urate-lowering therapy.”

Investigators also found stricter protocols excluding aggregates and focusing solely on grade 2 – 3 lesions resulted in 26% to 50.6% deposition rates. However, this was not confirmed with microscopy. Another noteworthy finding was a shorter 4-joint protocol for knees and 1MTPs was comparable to the extended 10-joint one in gout.

The team wrote how the next step is to conduct longitudinal studies to understand the ultrasound results and what it means for asymptomatic hyperuricemia detection. The current study was limited by having no microscopy proof of sonographic deposits, being unable to compare with other imaging methods such as DECT, and only having a moderate sample size—though the sample favored generalizability with participants from different settings.

Investigators said they needed to define which characteristics or clusters, such as serum urate levels, comorbidities, or genetics, favor monosodium urate crystal deposition in asymptomatic hyperuricemia. That way, they know what subjects would benefit from urate-lowering agents regarding preventing clinical gout or comorbidities.

“…Ultrasound seems an appropriate screening tool for [monosodium urate] crystal deposits in [asymptomatic hyperuricemia], as it is non-invasive, non-ionizing, patient-friendly and highly accessible, with good intra and interrater reliability,” investigators wrote. “However, as our work brings to light, an accurate sonographic definition of [monosodium urate] crystals presence in subjects with [asymptomatic hyperuricemia] is required.”

References

1. ^{Peral-Garrido ML, Gómez-Sabater S, Caño R, et al. Prevalence of crystal deposits in asymptomatic hyperuricemia according to different scanning definitions: A comparative study. Semin Arthritis Rheum. Published online June 20, 2024. doi:10.1016/j.semarthrit.2024.152470}
2. ^{Mount, D. Asymptomatic Hyperuricemia. UpToDate. April 11, 2023. https://www.uptodate.com/contents/asymptomatic-hyperuricemia#H75373331. Accessed July 2024.}