Background: To decrease the burden of disease of rheumatoid arthritis (RA), patients at risk for RA need to be identified as early as possible, preferably when no clinically apparent synovitis can be detected. Up to now, it has been fairly difficult to identify those patients with arthralgia who develop inflammatory arthritis (IA), but recent studies using ultrasound (US) suggest that earlier detection is possible. We aimed to identify patients with arthralgia developing IA within 1year using US to detect subclinical synovitis at first consultation. Methods: In a multi-centre cohort study, we followed patients with arthralgia with at least two painful joints of the hands, feet or shoulders without clinical synovitis over 1year. Symptom duration was<1year, and symptoms were not explained by other conditions. At baseline and at 6 and 12months, data were collected for physical examinations, laboratory values and diagnoses. At baseline, we examined 26 joints ultrasonographically (bilateral metacarpophalangeal joints 2-5, proximal interphalangeal joints 2-5, wrist and metatarsophalangeal joints 2-5). Scoring was done semi-quantitatively on greyscale (GS; 0-3) and power Doppler (PD; 0-3) images. US synovitis was defined as GS≥2 and/or PD≥1. IA was defined as clinical soft tissue swelling. Sensitivity and specificity were used to assess the diagnostic value of US for the development of IA. Univariate logistic regression was used to analyse the association between independent variables and the incidence of IA. For multivariate logistic regression, the strongest variables (p<0.157) were selected. Missing values for independent variables were imputed. Results: A total of 196 patients were included, and 159 completed 12months of follow-up. Thirty-one (16%) patients developed IA, of whom 59% showed US synovitis at baseline. The sensitivity and specificity of US synovitis were 59% and 68%, respectively. If no joints were positive on US, negative predictive value was 89%. In the multivariate logistic regression, age (OR 1.1), the presence of morning stiffness for>30minutes (OR 3.3) and PD signal (OR 3.4) were associated with incident IA. Conclusions: The presence of PD signal, morning stiffness for>30minutes and age at baseline were independently associated with the development of IA. Regarding the value of US in the diagnostic workup of patients with early arthralgia at risk for IA, US did perform well in ruling out IA in patients who did not have US synovitis.

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Keywords Arthralgia, Inflammatory arthritis, Power Doppler, Ultrasonography
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Journal Arthritis Research & Therapy
van der Ven, M, van der Veer-Meerkerk, M. (M.), ten Cate, D.F, Rasappu, N. (N.), Kok, M.R, Csakvari, D. (D.), … Luime, J.J. (2017). Absence of ultrasound inflammation in patients presenting with arthralgia rules out the development of arthritis. Arthritis Research & Therapy, 19(1). doi:10.1186/s13075-017-1405-y