CO:10:5 | Beyond major glands: high-resolution ultrasound mapping of labial salivary and lacrimal gland involvement in Sjögren’s disease

Giovanni Fulvio¹, Rossana Izzetti², Valentina Donati³, Caterina Porciani⁴, Silvia Fonzetti¹, Gaetano La Rocca¹, Beatrice Dei¹, Francesco Ferro¹, Marta Mosca¹, Chiara Baldini¹. | ¹Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa; ²Unit of Dentist, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine University of Pisa; ³Azienda Ospedaliero-Universitaria Pisana, Unit of Pathological Anatomy, Pisa; ⁴Immunology and Allergology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy

Background: Ultra-high frequency ultrasound (UHFUS) has emerged as a valuable tool for assessing the lacrimal glands (LGs) and labial salivary glands (LSGs) in patients with Sjögren’s disease (SD). However, only a few studies have investigated the diagnostic utility of evaluating these two gland types in combination. This study aimed to determine whether assessing both the number of glands involved and the severity of their involvement, based on the presence of very hypoechoic areas (VHA), could enhance diagnostic accuracy and support phenotypic stratification in patients with suspected SD.

Methods: Consecutive patients with suspected SD, undergoing LSG biopsy, were included. LSGs and LGs were examined using 48 MHz and 18 MHz probes, respectively. Glandular inhomogeneity was evaluated using a semiquantitative OMERACT score ranging from 0 to 3 for each gland, and a combined score for the LSGs and LGs was calculated (range 0–6). We specifically investigated the presence of very hypoechoic areas ( either lymphoma pattern and/or multiple very hypoechoic areas pattern (1,2)). Serum from each patient was tested for anti-Ro52, anti-Ro60, and anti-SSB/La abs, evaluating the quantitative titer of the autoantibodies with band densitometry.

Results: A total of 71 subjects (10 males, 61 females) were enrolled in the study, of whom 28 fulfilled the ACR 2016 classification criteria for Sjögren’s disease (SD). Cohen’s kappa analysis demonstrated moderate concordance in grayscale assessment between LGs and LSGs (k = 0.600, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that both LG and LSG UHFUS scores, using an optimal cut-off of 2, could effectively differentiate patients with SD from sicca controls, with area under the curve (AUC) values of 0.836 (95% CI: 0.702–0.970) and 0.899 (95% CI: 0.807–0.991), respectively. The combined score yielded excellent diagnostic accuracy (AUC = 0.909, 95% CI: 0.820–0.997; Fig. 1, A-B). All individuals with UHFUS scores >2 in both LGs and LSGs were diagnosed with SD. Patients exhibiting positive UHFUS findings in both gland types ('double positive') displayed significantly higher levels of tissue inflammation, autoantibody titers, and ESSDAI scores compared to those with abnormalities limited to a single gland type. Conversely, patients with UHFUS scores <2 across all glands had the lowest levels of inflammatory biomarkers and autoantibody titers (Fig. 1, C). An increasing burden of VHAs was associated with elevated histological inflammatory markers, autoantibody titers, immunoglobulin levels, and ESSDAI scores, while C4 and lymphocyte counts decreased accordingly (Fig. 1, D).

Conclusions: Evaluating multiple exocrine glands increases diagnostic power. Furthermore, as in joint ultrasound, a higher number and greater severity of exocrine gland abnormalities is associated with increased systemic disease activity and heightened biohumoral responses.

References. 1) Lorenzon et al., CER, 2021 2) Fulvio et al., CER 2022.