Research Article
Is the Semiquantitative Gray Scale Grading and spectral Doppler of Salivary Glands Useful in Primary Sjogrens Syndrome?
Jose Alexandre Mendon�a*, Caique Chagas Cavuto, Isabella Siste de Almeida Aoki, Rafael de Figueiredo Torres Caivano and Isabella Casani Rech
Corresponding Author: Jose Alexandre Mendonca, Rheumatology Service, Pontifical Catholic University of Campinas, Sao Paulo, Sumare, CEP, 13175-665, Brazil,
Received: July 31, 2020; Revised: August 21, 2020; Accepted: August 19, 2020 Available Online: October 09, 2020
Citation: Mendonca JA, Cavuto CC, Aoki ISDA, Caivano RDFT & Rech IC (2021) Is the Semiquantitative Gray Scale Grading and spectral Doppler of Salivary Glands Useful in Primary Sjogrens Syndrome?Gray Scale and Spectral Doppler of Salivary Glands in Sjogrens Syndrome. J Rheumatol Res, 3(1): 161-168.
Copyrights: �2021 Mendonca JA, Cavuto CC, Aoki ISDA, Caivano RDFT & Rech IC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Background: Salivary Gland Ultrasonography (SGUS) is very useful in the diagnosis of patients with Sjogren’s Syndrome (SS). The spectral Doppler (SD) is a supplementary tool to the gray scale (GS) that can potentially quantify the inflammatory processes through the resistance index (RI).

Objective: To determine the diagnostic capacity of SGUS jointly with SD indices, correlating with the clinic and laboratory data, of the glandular inflammatory process in patients with primary Sjogren’s Syndrome (PSS).

Methods: In this cross-sectional study, we performed SGUS of 17 patients with pSS according to the ACR-EULAR 2016 diagnostic criteria. The echotexture of the parotid and submandibular glands was graded from 0 to 4, according to the degree of injury; through the use of SD we evaluated the glandular blood flow and calculated the RI of parenchymal vessels. Spearman's correlation coefficient was used to correlate clinical, laboratory and imaging variables.

Results: A total of 17 patients diagnosed with PSS, Caucasian, female, who suffered from xerophthalmia and xerostomia. Out of these, 15 (88.23%) had positive anti-Ro/SSA and 11 (64.70%) had positive anti-La/SSB. SGUS was used with 16 patients (94.11%) with grades ≥2, suggesting parenchyma heterogeneity characteristic of pSS. The average RI value found in our sample was 0.57 ± 0.10. Spearman's correlations between ultrasound (US) and laboratory variables showed statistical significance between SGUS with ESR (r=0.771 and p<0.00) and anti-La/SSB (r=0.499 and p=0.04). The RI showed statistically significant correlations with the C-RP (r=-0.647 and p=0.01) and anti-La/SSB (r=-0.647 and p=0.01).

Conclusion: SGUS, together with SD, can be considered a promising tool in the hemodynamic evaluation of the major salivary glands inflammatory process in patients with pSS.

Keywords: Sjogren’s syndrome, Ultra Sonography, Spectral Doppler, Resistive Index
Abbreviations: PSS: Primary Sjogren's syndrome; JSS: Juvenile Sjogren's syndrome; ACR: American College of Rheumatology; EULAR: European League Against Rheumatism; US: Ultrasound; RI: Resistance Index; SGUS: Salivary Gland Ultra Sonography; SD: Spectral Doppler; GS: Gray Scale; ESR: Erythrocyte Sedimentation rate; C-RP: C-reactive protein; RF: Rheumatoid Factor; ANA: Antinuclear antibody

Primary Sjogren's syndrome (pSS) is a chronic and autoimmune inflammatory disease, affecting exclusively the exocrine glands, and causing a gradual loss of glandular secretory function and an increased risk of malignancy of B-cell non-Hodgkin’s lymphoma. The disease commonly develops with xerostomia and xerophthalmia [1]. It has a higher prevalence in women (10:1) and is diagnosed at a mean age of 53 years [2]. Lymphoplasmacytic infiltration is considered responsible for glandular hypo function [3]. Currently, PSS diagnosis can be made using the ACR-EULAR 2016 PSS classification criteria [4].

Ultrasound (US) has been increasingly used in the practice of rheumatology, since it is a simple exam, in real time, without ionizing radiation and less expensive than other diagnostic imaging methods [5]. Therefore, in order to improve the diagnosis [6] and monitor the therapeutic response [7], salivary gland ultrasound (SGUS) has revealed to be an instrument capable of assessing the involvement of salivary glands in a less invasive manner [8,9]. Several assessment systems have been developed for the use of SGUS, all of them highly specific, regardless of the score used [10]. SGUS’s weight can be considered similar to the minor criteria of the ACR-EULAR consensus [11].

The spectral Doppler (SD), in addition to the gray scale (GS), is used to assess glandular vascularization [12,13]. The inflammatory process, by increasing glandular perfusion, generates hypervascularization and stimulates angiogenesis, resulting in hemodynamic changes measured by the variation in the resistance index (RI) [10].
The objective of this study was to evaluate the diagnostic potential and the supplementary use of SGUS plus SD to correlate SGUS+SD with the presence of glandular inflammatory process in patients with pSS.


Study population
This cross-sectional study was carried out at the Rheumatology Outpatient Clinic of the Pontifical Catholic University of Campinas from March 2017 to December 2019. High-resolution SGUS images of 17 patients diagnosed with PSS were evaluated using SD.

The diagnosis of PSS was performed according to the ACR-EULAR 2016 classification criteria. The added score ≥4 of the following items determines the diagnosis: labial salivary gland with focal lymphocytic sialoadenitis and focus score ≥1 (3 points), anti-Ro/SSA positive (3 points), ocular staining score ≥5 (or van Bijsterfeld score ≥4) in at least one eye (1 point), Schirmer's test ≤ 5 mm/5 min in at least one eye (1 point) and total unstimulated saliva flow ≤0.1 ml/min (1 point).

Patients with a previous diagnosis of any of the following conditions were excluded from the study: history of head and neck radiation therapy, active hepatitis C infection (positive C-RP), Acquired Immuno Deficiency Syndrome (AIDS), Sarcoidosis, Amyloidosis, graft versus host or IgG4-related disease.
This study was approved, on May 2, 2016, by the Human Research Ethics Committee of the Pontifical Catholic University of Campinas (opinion number 1.526.307).

Clinical and laboratory assessment
A standardized clinical evaluation was carried out and the following data was collected: Gender, age, ethnicity, duration of illness since diagnosis, clinical history of xerophthalmia and xerostomia.
The laboratory evaluation was performed by collecting the qualitative and quantitative values of autoantibodies Anti-Ro/SSA and Anti-La/SSB, Rheumatoid Factor (RF) and ANA. Nonspecific inflammatory markers were quantitatively assessed using the erythrocyte sedimentation rate (ESR) and C-reactive protein (C-RP).

Salivary gland scintigraphy
Scintigraphy of salivary glands was performed with sodium pertechnetate solution [99mTc] in all patients by the nuclear medicine service of Campinas. “Positive scintigraphy” was considered under the following circumstances: (1) delayed uptake, (2) reduced concentration and/or delayed radio tracing substance secretion, as described by the American European Criteria Group (AECG) 2002 [14].

Minor salivary gland biopsy (MSGB)
MSGB was performed in all patients by an experienced pathologist, from the pathology service of PUC-Campinas Hospital. The histopathological material was obtained from a sample of the lower lip region and classified according to the focus score described in previous studies, with ≥ 1 being considered as a positive biopsy and associated with the diagnosis of SS [15].

Ultrasound evaluation of salivary glands
For the SGUS exam, a high-resolution US equipment, MyLab50 (Esaote S.p.A., São Paulo, Brazil), with a 12 MHz high frequency linear probe, B mode, was used. The investigation was complemented with SD, using the following configurations: a frequency of 6.6-8.0 MHz, frequency repetition pulse, which varied from 0.5 Hz to 1.0 MHz and a low wall filter. US was used with all patients by the same operator, with 12 years of experience in SGUS tests, blind to the patients' clinical data. The clinical evaluation was performed by another rheumatologist.

The four major salivary glands (bilateral parotid and submandibular glands) were studied based on De Vita et al. criteria [9], as well as on the study by Cornec and his collaborators [10] and rated on a scale of 0 to 4 for echotexture, exemplified in Figure 1. Grade 0 represents normal gland. Grade 1 is attributed to glands that have small hypoechogenic areas without echogenic bands. When there are multiple hypoechogenic areas measuring 6 mm or multiple calcifications with echogenic bands. The highest value for each patient was considered to determine the patient's US classification. Scores ≥2 are considered positive for SGUS, illustrating echo graphic changes that suggest SS.
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