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Asymptomatic hyperuricaemia is defined as a serum urate concentration equal to or above 7.0 mg/dl with no symptoms or clinical signs. Most individuals with hyperuricaemia, however, do not develop gouty arthritis. The annual incidence of gout is 0.5% in subjects with uric acid levels from 7.0 to 8.9 mg/dl, rising to 4.9% in those with uric acid levels higher than 9.0 mg/dl.1 However, only 12% of patients with serum uric acid levels between 7 and 7.9 mg/dl who were followed for 14 years developed gout.2 There are no accurate predictors of gout in this population and, as a consequence, we ignore the patients who may benefit from an early urate-lowering therapy intervention. The aim of this pilot study was to investigate the prevalence of gout in patients with asymptomatic hyperuricaemia and to investigate the accuracy of ultrasound in the diagnosis of gout in this population. For this purpose, the presence of birefringent monosodium urate (MSU) crystals in the synovial fluid was used as a gold standard.
A total of 26 consecutive patients with a sustained serum urate concentration equal to or above 7.0 mg/dl documented at least twice in the last 2 years were included in this study (table 1). All patients denied having previous joint symptoms. A standardised ultrasonography assay was performed in the knees and feet to assess patients for the presence of ultrasound double contour sign (DCS) or hyperechoic cloudy area (HCA). Aspiration was guided by ultrasonography in every patient; the selected joint was chosen based on the ultrasound presence of a minor quantity of synovial fluid, Doppler signal, DCS or HCA. All microscopic observations were performed in the first 2 h after aspiration and evaluated for the presence of MSU crystals by two experienced, independent observers who were blinded to the ultrasound results. When a discrepancy occurred, a new examination was performed by both observers, and the consensus was accepted.
Ultrasound DCS or HCA was found in 11 out of these 26 patients, and MSU crystals were identified in 9 patients; the ultrasound sensitivity was 100%, specificity was 88.2%, positive predictive value was 81.8%, negative predictive value was 100% and positive-likelihood ratio was 5.5. The κ coefficient for inter-reader ultrasound images was 0.79–0.93.
The European League Against Rheumatism evidence-based recommendations for gout note that ‘the demonstration of MSU crystals in synovial fluid or tophus aspirates permits a definitive diagnosis of gout’.3 In a previous study, using joint puncture, crystals could be identified in one out of 19 healthy subjects with asymptomatic hyperuricaemia (5%) and in two of nine (22%) hyperuricaemic patients with renal failure.4 Our higher prevalence, 9/26 (34.6%), could be a result of the use of ultrasound in the selection of the area of aspiration. The diagnostic validity of ultrasound in gout has been demonstrated5,–,8; the presence of DCS has a sensitivity of 43% and a specificity of 99%,8 and the occurrence of HCA has a sensitivity of 79% and a specificity of 95%.5 Two prior studies using ultrasound in asymptomatic hyperuricaemia revealed gout by the presence of suggestive lesions in 25%–34% of patients.9 10 The main limitation of both studies was that the presence of MSU crystals was not proven. As far as we know, this is the first study to demonstrate that the presence of DCS and HCA ultrasound findings is associated with MSU crystals in the same joint in asymptomatic hyperuricaemia and, therefore, that ultrasound could be used for the diagnosis of gout. However, more data are necessary to confirm that ultrasound is a useful tool for the early diagnosis and prevention of structural damage in patients with gout.
We are indebted to the Metabolic Vascular Unit research manager Dña. Carolina Velasco García and to the nursing staff (Inés Narillos and Arantxa Sánchez) for excellent patient care and follow-up.
Funding This study was supported by grants from the National Health Service: Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (FIS, 08/0009), the Red Española de Atención Primaria (2009/70) and RECAVA (RD06/0014/0019).
Competing interest None.
Patient consent Obtained.
Ethics approval This study was conducted according to local regulations and the declaration of Helsinki, and local approval was obtained from the ethical committee and the Institutional Review Board of the Hospital Universitario La Paz, Madrid, Spain.
Provenance and peer review Not commissioned; externally peer reviewed.
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