Ultra-High Frequency Ultrasonography of Labial Salivary Glands: Diagnostic and Prognostic Value in Sjögren’s Syndrome

Background Recently, a growing interest has arisen in last generation ultra-high frequency ultrasonography (UHFUS) that can achieve tissue resolution up to 30 µm, opening up new possibilities for the study of labial salivary glands (LSGs). Aims of the study The objectives of the study were to describe relationship between UHFUS findings of LSGs and primary Sjögren’s Syndrome (pSS) patients’ clinical manifestations, different serotypes, LSGs histological features and lymphoproliferative risks. Eventually we aimed to explore diagnostic UHFUS accuracy to predict primary Sjögren’s Syndrome. Materials and methods At Rheumatology Unit of Pisa, in the work-up of pSS, UHFUS imaging is currently used to locate the LSG to do an ultrasound-guided biopsy. UHFUS of LSGs was performed with a 70 MHz probe, scanning first the central compartment of the inferior lip, and then both peripheral compartments. Patients with suspected pSS, from Jan 2018 to Jun 2022, were enrolled in the study. For each patient, we assessed LSG inhomogeneity applying OMERACT score (from 0 normal to 3 evident inhomogeneity). Laboratory tests, clinical manifestations, and histological features were also collected. pSS diagnosis was made accordingly with ACR/EULAR criteria. Results 216 subjects were enrolled: 117 pSS patients and 99 sicca controls. In the whole study population, UHFUS Score was positively associated with ESSDAI and IgG level. Ro-52+/Ro-60+ serotype was more frequently detected in patients with a higher UHFUS score, otherwise seronegative Ro-52-/Ro-60- serotype was more frequently detected in patients with a lower UHFUS score. Number of foci, focus score and ectopic lymphoid structures were significatively higher in patients with UHFUS score 3. On the other hand, UHFUS score 3 was usually associated with a positive biopsy with or without a high degree of inflammation (1≤FS<3 or FS≤3), the last one known lymphoma risk factor. UHFUS score 3 was associated with further lymphoma risk factors: C4 hypocomplementemia, glandular swelling and lymphadenopathic domain. Furthermore, UHFUS score 0 provided high negative predictive value, a score 3 provided a high positive predictive value. Interestingly, in SSA- patients, with an optimal cut-off equal to 2, UHFUS presented high negative predictive value. Discussion In conclusion, higher UHFUS score are associated with high disease activity measured by ESSDAI, Ro-52/Ro-60+ serotype, higher degree of inflammation and clinical risk factors for lymphoma. In addition, UHFUS is a could avoid biopsy in selected cases: Score 0 made pSS diagnosis unlikely, a Score 3 very likely. Finally, in SSA- patients, UHFUS Score