FRI0153 ULTRA HIGH-RESOLUTION ULTRASOUND (UHFUS) OF LABIAL SALIVARY GLANDS: POTENTIAL APPLICATIONS IN PRIMARY SJÖGREN'S SYNDROME

Background:Major salivary gland ultrasonography has an established role in diagnosis and assessment of pSS. Nowadays, however, interest is also growing in last-generation ultra high resolution ultrasound (UHFUS) transducers, which can produce frequencies up to 70 MHz and achieve tissue resolution up to 30 μm, opening up new possibilities for the study labial salivary glands (LSG).Objectives:To investigate the usefulness of UHFUS in LSG ultrasound-guided biopsy and preoperative planning.Methods:Consecutive patients undergoing a LSG for clinically suspected pSS were included in this study from January 2018 to December 2019. UHFUS of LSG was performed by using VEVO MD, equipped with a 70 MHz probe, scanning first the central compartment of the inferior lip, and then both peripheral compartments. The following parameters were evaluated: distribution of the glands, parenchymal inhomogeneity (score 0-3, from normal to evident), and fibrosis. UHFUS imaging was used to help locate the LSG for the US-guided biopsy. The same expert pathologist calculated the surface area of gland sections examined, the LSG focus score (FS), the number of foci and evaluated the presence of ectopic germinal centers (GCs). Consecutive patients that had undergone a traditional LSG biopsy from December 2016 to December 2017 were included as controls.Results:We included a total of 249 patients with suspected pSS: 137 undergoing the UHFUS-guided LSGs and 112 the traditional LSG biopsy procedure. No demographic differences were observed between the two groups. No differences were also observed in the distribution of the final diagnosis. A diagnosis of pSS according the ACR 2016 criteria was made in 60/137 (43.8%) and 36/112 (32.1%) patients, respectively whereas a diagnosis of no-SS sicca was made in 44/137 (32.1%) and in 43/112 (38.4%) patients; the remaining diagnosis included secondary SS (4/137, 3% and 9/112, 8%) and undifferentiated connective tissue disease (UCTD) (29/137, 21.2%, and 24/112, 21.4%). With respect to no-SS sicca controls and UCTD patients, pSS patients presented higher UHFUS inhomogeneity scores in both central and peripheral labial compartments (p=0.001). There were no complications from the HUFUS-guided LSG biopsy. The mean glandular surface area obtained was significantly higher than the area obtained by traditional LSG biopsy procedure (7.4 ±4.0 mm2vs 6.3±3.7 mm2, p=0.02) thus facilitating the assessment of the FS. Interestingly, the latter showed a good correlation with the UHFUS inhomogeneity (r=0.509**, p=0.000).Conclusion:UHFUS of LSG appeared feasible and sensitive in pSS, potentially offering unique advantages in LSG ultrasound-guided biopsy.Disclosure of Interests:None declare

POS0778 ULTRA HIGH-RESOLUTION ULTRASOUND (UHFUS) OF LABIAL GLANDS IS A STRONG PREDICTOR OF SALIVARY GLAND HISTOPATHOLOGY IN SJÖGREN'S SYNDROME (PSS)

Background:Last-generation ultra high-resolution ultrasound (UHFUS) transducers, producing frequencies up to 70 MHz and achieving tissue resolution up to 30 μm, are opening up new possibilities for the study of labial salivary glands (LSG) in patients clinically suspected with primary Sjögren's syndrome (pSS).Objectives:To explore the value of LSG-UHFUS as a predictor of the intensity of the histological inflammation in LSG biopsy in an inception cohort of patients with sicca symptoms derived from daily clinical practice.Methods:Consecutive patients undergoing a LSG for clinically suspected pSS were included in this study from January 2018 to October 2020. UHFUS of LSG was performed by using VEVO MD, equipped with a 70 MHz probe, scanning first the central compartment of the inferior lip, and then both peripheral compartments. Parenchymal homogeneity was graded on a scale of 0 (normal) to 3 (evident). UHFUS imaging was used to locate the LSG for the US-guided biopsy. For each of the LSG specimens the area of the glandular tissue, the presence and number of foci and the focus score (FS) were assessed. Immunostaining for CD21 was performed to evaluate the presence of follicular dendritic cells (FDC) in foci.Results:We included a total of 171 patients with suspected pSS: out of them, 83 (48.5%) received a diagnosis of pSS (ACR 2016 criteria) and 88 (51.5 %) were diagnosed as no-SS sicca controls. Out of the 171 LSG biopsies, 73/171 (42.7%) were characterized by a nonspecific chronic sialadenitis (NSCS) whereas a focal lymphocytic sialadenitis (FLS) was described in the remaining 98/171 (57.3%). UHFUS-LSG scores were differently distributed in pSS patients with respect to no-SS sicca controls: a score 0 was detected in 16/88 no-SS sicca controls and in none of the 83 pSS patients, whereas a score 3 was detected in 12/83 pSS and in none of no-SS sicca controls. (p<0.001). The higher was the UHFUS grading, the higher was the number of foci (from a mean (S.D) = 0.38 (0.72) in UHFUS-score 0 to 4.58 (3.11) in UHFUS-score 3, p<0.001) and the focus score (from 0.17 (0.32) in UHFUS-score 0 to 1.88 (0.90) in UHFUS-score 3, p<0.001) of the samples. Overall, out of the 16 no-SS controls with LSG-UHFUS score 0, only 4/16 showed histological features of focal lymphocytic infiltrate; however, the mean FS of those 4/16 samples was 0.17 (0.32). In fact, considering a FS≥1, negative UHFUS-LSG was highly predictive of a negative histology (100 %). By contrast, out of the 12 pSS patients with the highest score at LSG-UHFUS (score 3), 10/12 presented FDC networks in their biopsies, with a positive predictive value of 83% of the severity of the infiltrate.Conclusion:UHFUS of LSG appeared feasible and sensitive in pSS; due to its striking negative predictive value this novel tool can help to identify negative patients on subsequent lip biopsy, thus avoiding invasive procedures in selected cases. Besides its diagnostic role, considering the association with the presence of FDC networks, UHFUS-LGS may also have a role in patients prognostic stratification.Disclosure of Interests:None declare

POS0782 FOLLICULAR DENDRITIC CELL NETWORKS IN MINOR SALIVARY GLAND BIOPSIES: A MARKER OF DISEASE ACTIVITY AT BASELINE AND DURING THE FOLLOW-UP IN SJÖGREN'S SYNDROME

Background:Minor salivary gland biopsy (MSGB) has been increasingly recognized as an important tool for the stratification of patients with primary Sjögren's syndrome (pSS). Recently, the presence of follicular dendritic cell (FDC) networks in the inflammatory infiltrate has been associated with more severe biological and serological abnormalities compared with less organized infiltrates.Objectives:To investigate the associations between the presence and number of FDC networks in foci and pSS glandular and extra-glandular disease activity at baseline and during the follow-up.Methods:Consecutive MSGBs performed in daily practice for clinically suspected pSS from January 2017 to October 2020 were reviewed. Patients' demographic, clinical, biological and serological data were obtained from medical records. The ESSDAI was used to measure disease activity at baseline and at the end of the follow-up in pSS patients. For histopathology, 3 µm sections were cut from each formalin-fixed paraffin-embedded block of MSGBs and stained with haematoxylin and eosin (H&E). Immunohistochemical stainings were performed on additional 3 μm sections in order to detect T lymphocytes (CD3), B lymphocytes (CD20) and follicular dendritic cells (CD21). Glandular tissue areas, number of foci, focus score (FS) and the presence and number of FDC networks were assessed.Results:We reviewed 330 consecutive MSGBs from patients with suspected pSS: out of them 146/330 (44%) were classified as nonspecific chronic sialadenitis (NSCS) whereas 184/330 (56%) as focal lymphocytic sialadenitis (FLS). According to the ACR/EULAR criteria the diagnosis of pSS was confirmed in 130 patients (117 F:13 M, age 56±13 yrs). The mean (S.D) surface area of the MSGBs was 7.8 (3.9) mm2. The number of foci in the FLS samples ranged from 1 to 12 (mean (S.D)=3.1 (2.6)), whereas the FS ranged from 0.3 to 9.0 (mean (S.D) = 1.4 (1.2)).The presence of FDC networks was documented in 106/330 (32%) of the samples; in 54/106 (51%) of these MSGBs the number of FDC networks ranged from 2 to 8 (mean (S.D)=3.1 (1.4)). The number of FDC networks significantly correlated with the number of foci (r=0.721**) and FS (r=0.707**). Patients with FDC networks in the inflammatory infiltrate presented more serological abnormalities (i.e anti-Ro/SSA, anti-LA/SSB, Rheumatoid factor) and elevated IgG levels (p<0.001). In pSS patients, the number of FDC networks slightly correlated also with C4 levels (r=-0.216*), peripheral lymphocyte count (r=-0.274**) and with glandular (r=0.213*), and biological (r=0.230**) domains of the ESSDAI at baseline. After a mean (S.D) follow-up of 21(13) months, the number of FDC networks still correlated with the final total ESSDAI (r=0.312**).Conclusion:The presence and number of FDC networks in foci represent a useful histopathological parameter able to reflect disease activity at baseline and during the follow-up, thus allowing more personalized interventions.Disclosure of Interests:None declare

Ultra-high frequency ultrasonography (UHFUS)-guided minor salivary gland biopsy: A promising procedure to optimize labial salivary gland biopsy in Sjögren’s syndrome

Background: Sjögren's syndrome (SS) is an autoimmune disease characterized by an inflammatory infiltrate of exocrine salivary and lachrymal glands. Diagnosis is complex, and minor salivary gland biopsy and subsequent focus score (FS) calculation appear of extreme importance in the diagnostic work-up of the disease. Ultra-high frequency ultrasonography (UHFUS) is a recently introduced diagnostic technique, which is gaining an increasingly important role in intraoral imaging. This study aims at exploring the usefulness of UHFUS for obtaining valuable labial salivary gland samples to assess the histopathological features of SS patients. Methods: Patients with clinical suspect of SS and eligible for minor salivary gland biopsy were enrolled. UHFUS scan of the lower lip was performed. Glandular echostructure was classified according to Outcome Measures in Rheumatology (OMERACT) scoring system. The glands to be sampled were selected on the basis of UHFUS evaluation and biopsied. The areas of the samples were recorded and compared with those obtained without UHFUS guidance. The correlation between UHFUS grade and labial gland FS was also assessed. Results: The areas of the samples obtained with UHFUS guidance were significantly higher (7.25&nbsp;±&nbsp;3.98&nbsp;mm2) than those obtained by conventional procedures (5.79&nbsp;±&nbsp;3.49&nbsp;mm2, P&nbsp;=.02). UHFUS correlated significantly with the salivary gland FS (r&nbsp;=.532, P&nbsp;=.001). Conclusion: UHFUS seems a promising tool in SS diagnostic algorithm, being able to provide a valuable support to the biopsy procedure. Further studies are mandatory to confirm the role of UHFUS in SS

One year in review 2021: systemic vasculitis

Large- and small-vessel vasculitis are complex potentially life-threatening systemic autoimmune diseases that have recently been subjected to considerable immunologic and clinical research.Following the other reviews of this series, here we aim to summarise some of the most significant studies that have been recently published on the pathogenesis, clinical features and novel treatments of systemic vasculitis