Often, semi-quantitative synovial grading schemas combine common aspects of these patterns into a summed “synovitis” score. Using a three-component summed score, Krenn and colleagues

determined that on average the synovitis of OA is low-grade in comparison to the high-grade synovitis of RA, but still distinguishable from normal SM [56], [77] and [97]. These specific histopathologic patterns of synovitis have not yet provided strong links to clinical disease patterns or specific disease mechanisms. However, the presence of inflammatory synovial infiltrates has been associated with worse knee symptom scores PD-1/PD-L1 mutation measured by patient administered questionnaires [87], and the specific cellular nature of inflammatory infiltrates may differ between primary OA and

OA secondary to conditions such as hemachromatosis [42]. These studies point to the possibility that more in depth assessment of synovial histopathology may provide insights into disease variability or targetable mechanisms in the future. Although in some joints moderate to large synovial effusions can be identified with routine X-ray techniques, in most cases, detection of the anatomically limited synovitis that is characteristic of OA requires advanced imaging techniques such as MRI and US. There are multiple MRI-based “whole-organ” grading systems that score specific anatomic features in the Selleck Epacadostat joint, including semi-quantitative characterization of the magnitude of synovial change [45] and [78]. The most commonly used methods define synovitis according to the extent of synovial cavity distension or total synovial volume. These systems have been mostly applied to non-contrast imaging, but more recent studies have incorporated the use of contrast-enhanced MR imaging techniques to distinguish synovial thickening from effusion [31] and [39]. For example, in a recent study by Roemer et al. [85], the authors used both contrast-enhanced and non-enhanced images to examine a group of subjects with knee OA, and noted that synovitis was

present in over 95% of the knee joints with an effusion, but also in 70% of knee joints in patients without an effusion. These Casein kinase 1 findings suggest that in many cases synovial thickening may be independent of effusion, and may perhaps be a more reliable indicator of intra-articular pathology than the presence of joint effusion. Ultrasound has also been utilized to define the presence of synovitis in OA patients, and at least one report indicates that contrast-enhanced US may be as sensitive as contrast-enhanced MRI in detecting synovitis [99]. Whether synovitis defined by imaging approaches corresponds to specific histologic features has been addressed by at least three groups. In 1995, Fernandez-Madrid et al. demonstrated that areas of synovitis observed on MR images in patients with knee OA corresponded to a low-grade chronic synovitis histologically [30].