Abstract
Anti-citrullinated protein antibodies (ACPA) often precede onset of rheumatoid arthritis (RA) by years, and there is an urgent clinical need for predictors of arthritis development among such at-risk patients. This study assesses the prognostic value of ultrasound for arthritis development among ACPA-positive patients with musculoskeletal pain. We prospectively followed 82 ACPA-positive patients without clinical signs of arthritis at baseline. Ultrasound at baseline assessed synovial hypertrophy, inflammatory activity by power Doppler, and erosions in small joints of hands and feet. We applied Cox regression analyses to examine associations with clinical arthritis development during follow-up (median, 69 months; range, 24–90 months). We also compared the ultrasound findings among the patients to a control group of 100 blood donors without musculoskeletal pain. Clinical arthritis developed in 39/82 patients (48%) after a median of 6 months (range, 1–71 months). One or more ultrasound erosions occurred in 13/82 patients (16%), with none in control subjects (p < 0.001). Clinical arthritis development was more common among patients with baseline ultrasound erosions than those without (77 vs. 42%, p = 0.032), and remained significant in a multivariable Cox regression analysis that included previously described prognostic factors (HR 3.9, 95% CI 1.6–9.4, p = 0.003). Ultrasound-detected tenosynovitis was more frequent among the patients and associated with clinical arthritis development in a univariable analysis (HR 2.5, 95% CI 1.1–5.7, p = 0.031), but did not remain statistically significant in multivariable analysis. Thus, bone erosions detected by ultrasound are independent predictors of clinical arthritis development in an ACPA-positive at-risk population.Trial Registration: Regional Ethics Committee in Linköping, Sweden, Dnr M220-09. Registered 16 December 2009, https://etikprovningsmyndigheten.se/.
Highlights
Ultrasound Erosions in At-Risk Patients. Autoimmune features, such as the presence of circulating rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), typically precede the onset of clinically manifest rheumatoid arthritis (RA) [1, 2], as defined by the 1987 American College of Rheumatology (ACR87) or the 2010 ACR/EULAR classification criteria [3, 4]. Neither of these RA classification criteria is applicable to patients who are suffering from musculoskeletal (MSK) pain in the absence of clinical synovitis
The addition of power Doppler (PD) to Gray scale (GS) ultrasound findings allows for the detection of hyperemia, which is a sign of active inflammation [9]
After including potential confounders in the Cox regression model, the association between ultrasound-detected erosions and arthritis development remained statistically significant (HR 3.9, 95% CI 1.6–9.4, p = 0.003) (Figure 2)
Summary
Autoimmune features, such as the presence of circulating rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), typically precede the onset of clinically manifest rheumatoid arthritis (RA) [1, 2], as defined by the 1987 American College of Rheumatology (ACR87) or the 2010 ACR/EULAR classification criteria [3, 4]. Neither of these RA classification criteria is applicable to patients who are suffering from musculoskeletal (MSK) pain in the absence of clinical synovitis. Previous smaller studies have suggested that SH, in the toes, may occur frequently in control populations without clinical arthritis [12, 14, 16]
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