Ultrasonographic Evaluation of Salivary Glands for Sjogren's Syndrome: Diagnostic and Monitoring Insights

Summary

Salivary gland ultrasonography is a promising tool for the diagnosis and evaluation of disease activity and complications in Sjogren's syndrome (SS). The scanning technique for salivary gland ultrasound examination relevant to SS is described in the article.

Abstract

Sjogren's syndrome (SS) is a chronic autoimmune condition commonly affecting the exocrine glands, causing oral or ocular dryness and extraglandular manifestations including arthralgia, cytopenia, and lymphoma. The presence of autoantibodies against SSA/Ro, labial salivary gland biopsy, ocular staining, Schirmer's test, or salivary flow assessment are included in the current classification criteria of SS. However, the availability and invasiveness of these procedures limit their widespread use in clinical settings. Salivary gland ultrasonography (SGUS) is a non-invasive imaging modality for the evaluation of the salivary gland parenchyma and is increasingly utilized to aid diagnosis and monitoring in SS.

This article presents the protocol of SGUS for image acquisition at the parotid and submandibular glands. The objective is to present a standardized, reproducible, and practical approach to diagnostic SGUS for SS in daily clinical settings. Major salivary glands are scanned in a stepwise approach, beginning at the angle of the mandible for the superficial lobe of the parotid gland, followed by the deep lobe below the ramus of the mandible. Submandibular areas are then scanned for the submandibular glands. The steps in obtaining salivary gland images at each anatomical site are explained in the accompanying video. The echogenicity and echotexture at the thyroid gland are taken as a reference. The homogeneity, the presence and distribution of hypoechoic areas within the glands, and the border of the salivary glands are examined. The sizes and features of intra-/peri-glandular lymph nodes are recorded. The most distinctive sonographic feature in SS is glandular heterogeneity with the presence of hypoechoic/hyperechoic areas within the glands.

In summary, while SGUS cannot diagnose SS on its own, it can supplement the current classification criteria of SS and guide the clinical decision for salivary gland biopsy to support the diagnosis of SS in patients with sicca syndrome or suspicious systemic features, combined with autoantibody testing.

Introduction

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration in exocrine glands, including the salivary and lacrimal glands. Xerostomia, keratoconjunctivitis sicca, and extraglandular manifestations, including arthralgia, cytopenia, and lymphoma, are described in patients with SS. SS can be divided into primary and secondary types, in which the latter occurs in association with other connective tissue diseases. In the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for primary SS, anti-SSA/Ro positivity and lymphocytic infiltration in labial salivary gland biopsy contributed to the two major criteria, whereas Schirmer's test, ocular staining score, and unstimulated salivary flow represented the rest of the minor criteria¹. The criteria are summarized in Table 1. Labial biopsy is an invasive procedure with potential complications, including sampling error, sensory loss, and hematoma formation². Ocular staining tests and salivary flow assessment require specialized settings and might not be widely available.

Salivary gland ultrasonography (SGUS) is a non-invasive imaging modality that provides a detailed examination of the superficial salivary gland structure, which is commonly affected in patients with SS. Lymphocytic infiltration and inflammation in the salivary glands often lead to fatty infiltration, fibrosis, and loss of parenchyma, resulting in parenchymal inhomogeneity detected in SGUS³. The Outcome Measures in Rheumatology Clinical Trials (OMERACT) working group derived an ultrasound scoring system from grades 0 to 3 to semi-quantify inhomogeneity and the presence of hypoechoic areas within the parotid or submandibular glands⁴. A cutoff of grade 2 or above in at least one gland was found to correlate with positive labial biopsies, sialometry, and positive autoantibodies⁵. It demonstrated excellent specificity and good sensitivity in fulfilling the 2016 ACR/EULAR classification criteria for primary SS when given similar weight as the minor criteria. This protocol presents a standardized and practical approach for diagnosing SGUS in SS in clinical settings.

Protocol

The protocol demonstrated a clinical protocol for conduction of SGUS and the demonstration of scanning is performed on a de-identified healthy volunteer. Ethical approval is not required as the study is beyond the common rule and FDA definition of human research subject. Verbal consent from patients was obtained for taking clinical photos and their publication.

1. Transducer and machine settings

1. Select a high-frequency linear transducer of 10 MHz (see the Table of Materials).
2. Set to B mode.
3. Use the highest frequency of the probe.
4. Adjust the depth (3 cm) and gain (50%-60%).
   NOTE: The depth is usually 1 cm deeper than the target structure. Auto-gain function is available for some ultrasound consoles.
5. For a right-handed examiner, place the ultrasound machine next to the patient's right shoulder.

2. Patient preparation

1. Position the patient in the supine position with the neck slightly extended. Use a pillow to support the patient's head.
2. Remove any clothing or jewelry around the neck that may obstruct the ultrasound transducer.

3. Scanning of the thyroid gland

1. Orient the probe with the marker pointing towards the patient's right side for transverse images. For longitudinal scanning, orient the marker at the cephalic side.
2. Apply gel to the probe surface.
3. Place the probe below the thyroid cartilage for scanning of the thyroid gland. The right and left lobes of the thyroid gland are connected by the isthmus. Save the images and take the echogenicity of the thyroid gland as a reference (Figure 1).
4. If there is concomitant thyroid disease, compare the echogenicity to that of the surrounding muscles. Normal salivary glands are usually more echogenic than muscle.

4. Scanning of the parotid gland

1. Turn the patient's head to the opposite side of the gland being examined.
2. Place the transducer longitudinally along the anterior border of the parotid gland, just anterior to the ear and parallel to the tragus, moving from the superior to the inferior pole of the gland (Figure 2).
3. Place the probe transversely at the angle of the mandible to obtain the transverse scan. Ideally, the parotid gland is located between the mastoid and mandible ramus in transverse view. Scan the parotid gland transversely from the superior to the inferior pole (Figure 3).
4. Slide the probe below the ramus of the mandible to visualize the deep part of the parotid gland, which could be partially obscured by the mandible. Place the probe between the mastoid process and the angle of the mandible.
5. Save and label the images in both the longitudinal and transverse views.
6. Assess the size of the parotid gland.
7. Compare the echogenicity with that of the thyroid gland. The echogenicity of the normal parotid gland is similar to that of the thyroid gland.
8. The retromandibular vein and external carotid artery divide the superficial and deep parotid lobes. Turn on the color doppler to differentiate blood vessels from the dilated intraglandular duct.
9. Capture the degree of inhomogeneity, the clearness of the gland margin, and the presence of hypo-/an-echoic areas within the glands.
10. Note the presence of focal lesions and document the size, location, shape, and echogenicity. Turn on the color doppler to look for vascularity.
11. Score the degree of sonographic involvement on a scale of 0-3 as defined: Grade 0: normal, homogenous parenchyma; grade 1: mild inhomogeneity without hypo-/an-echoic areas; grade 2: moderate inhomogeneity with the presence of scattered hypo-/an-echoic areas; grade 3: Diffuse inhomogeneity with the presence of hypo-/an-echoic areas in the entire gland⁴.
12. The presence of lymph nodes within the parotid gland could be normal and common, especially when located in the superficial lobe. Measure the diameter of the lymph nodes. Evaluate the shape, echogenicity, and preservation of fatty hilum.
13. Repeat the scanning at the contralateral parotid gland. Compare the size and echotexture between the two parotid glands.

5. Scanning of the submandibular gland

1. Position the patient in the supine position with the head maximally tilted to the back.
2. To obtain the transverse view of the submandibular gland, position the transducer just below the angle of the mandible at the submandibular area, which is bounded by the mandible, mylohyoid muscles, and the anterior belly of the digastric muscles. Examine the entire submandibular gland from anterior to posterior (Figure 4).
3. Obtain the longitudinal view by placing the probe medial to the horizontal body of the mandible. Visualize the facial artery in this plane (Figure 5).
4. Save and label the images in both transverse and longitudinal views of the submandibular gland.
5. Assess the size of the submandibular gland.
6. Examine the echogenicity of the submandibular gland, which is usually less echogenic than the parotid gland.
7. Assess the degree of inhomogeneity, the clearness of the gland margin, and the presence of hypo-/an-echoic areas within the glands. Note the presence of focal lesions.
8. Grade the degree of inhomogeneity using the OMERACT score: Grade 0: normal parenchyma; Grade 1: minimal change with mild inhomogeneity without hypo-/an-echoic areas; Grade 2: moderate change with moderate inhomogeneity with focal hypo-/an-echoic areas; Grade 3: severe change with diffuse inhomogeneity with hypo-/an-echoic areas occupying all the surface of the gland. If the evaluation of the gland is not possible due to qualitative parameters, the fatty gland refers to grade 1, and the fibrous gland indistinguishable from adjacent tissue corresponds to grade 3⁴.
9. Measure the size of the submandibular lymph nodes. Evaluate the shape, echogenicity, and preservation of fatty hilum.
10. Repeat the scanning at the contralateral submandibular gland. Compare the size and echotexture between the two submandibular glands.

6. Documentation

1. Document the sonographic involvement on a scale of 0-3 at all four major salivary glands. A Score of ≥2 at any gland is considered compatible with SS.
2. Document the presence of lymph nodes if any. Record the diameter, shape, and whether fatty hilum is preserved.
3. Document the presence of focal abnormalities if any.

Results

Here we described the interpretation of salivary gland ultrasound images to aid diagnosis of SS. The anatomical annotation at the scanning sites is summarized in Figure 1, Figure 2, and Figure 3. The echotexture of the thyroid gland is taken as the reference. Normal parotid glands should appear homogeneous with clear demarcation with overlying tissues and muscles. The echotexture of normal parotid glands is comparable to that of the...

Discussion

Ultrasonography of the major salivary glands is a non-invasive and accessible imaging modality with high spatial resolution. The procedure of performing SGUS at the major salivary glands for patients with suspected SS is described in this article to facilitate reproducible and standardized examination. Parotid and submandibular glands are superficially located, which permits detailed examination by high-frequency ultrasound. SGUS is useful in evaluating various clinical conditions, including SS, sialadenitis, sialolithia...

Materials

Name	Company	Catalog Number	Comments
Examination couch		/	Quantity: 1
High frequency linear transducer of at least 10 MHz		SL2325 18-6 MHz linear transducer	Quantity: 1
Ultrasound console		Esaote my lab seven	Quantity: 1
Ultrasound gel		/	Quantity: 1