Is it so difficult to diagnose Sjogren's syndrome?

*Only for medical professionals to read for reference.
Non-invasive and convenient, can ultrasound carry the banner of pSS diagnosis? Sjogren’s syndrome (SS) is a chronic multi-system involved autoimmune disease, while primary Sjogren’s syndrome (pSS) is characterized by immune-mediated exocrine gland dysfunction and high activation of B cells.
Salivary gland involvement is The main clinical manifestations
.

At the 2021 Asia-Pacific Rheumatism Alliance (APLAR) Annual Meeting, Prof.
Helen Keen from Australia shared the topic of "Using Ultrasound Diagnosis in the Clinical Practice of Sjogren's Syndrome"
.

There are so many inspection methods for the small salivary glands.
According to the pSS diagnostic criteria and the population being studied, the prevalence of pSS is 0.
03%-2.
7%.
The incidence of pSS is more than that of men (female: male up to 10.
72), and the average age of onset is 56.
16 years old [1]
.

Because most of its clinical manifestations lack specificity, the diagnosis of pSS is more difficult
.

The prognosis of pSS itself is general, but it is necessary to assess the risk of non-Hodgkin's lymphoma in patients
.

The key to diagnosing and evaluating pSS is precisely the inconspicuous salivary glands
.

Doctors can diagnose salivary gland stones or other salivary duct blockages, salivitis, stenosis of salivary ducts, chronic inflammatory diseases or autoimmune diseases through imaging methods such as traditional parotid imaging, CT or MRI
.

Figure 1.
Salivary contrast results: (A) parotid contrast of healthy subjects; (B) punctate/spherical salivary gland swelling in pSS patients; (C) spherical/cavity salivary gland swelling in pSS patients; (D) Two-dimensional CT images of the parotid glands of patients with pSS; (E) Three-dimensional CT images of patients with pSS: the diameter of the large ducts is normal, the branch ducts are moderately narrow, and the salivary glands are enlarged [2]
.

Salivary gland imaging still has a certain missed diagnosis rate, and X-ray and CT have radiation, and contrast agents also increase the risk of allergic reactions
.

In addition to conventional imaging methods, ⁹⁹ᵐTc (technetium) isotope salivary gland imaging can also be used for pSS examination, which can be used to describe the uptake and exocrine situation of parotid and submandibular glands, diagnose obstruction, and distinguish some tumors
.

Figure 2.
Example of ⁹⁹ᵐTc (Technology) isotope salivary gland imaging [2] With different inspection methods, how valuable is it to diagnose pSS? According to the 2016 pSS classification criteria of the American Academy of Rheumatology and the European Union Against Rheumatism (ACR/EULAR), the diagnosis can refer to the following criteria [3]: ① A labial gland biopsy indicates focal lymphocytic infiltration, and a focal index ≥ 1 Foci/4mm2 ②Anti-Ro/SSA antibody positive ③At least one eye's conjunctival corneal staining score ≥5 or van Bijsterveld corneal and conjunctival staining score ≥4 ④Filter paper test at least one eye tear secretion test (Schirmer test) ≤5 mm/5 minutes ⑤No irritation Total saliva flow rate <0.
1ml/min.
Among them, ① and ② are 3 points, and ③, ④ and ⑤ are 1 point.
If the patient's cumulative score reaches 4 points or more, pSS can be diagnosed
.

It can be seen from the above that in the diagnostic criteria of ACR/EULAR, biopsy methods are often rejected by patients due to trauma.
People cannot help but start new explorations: Is there a more convenient and non-invasive diagnostic method? Ultrasound, how far is it from becoming the yyds in pSS? The salivary gland ultrasound examination of pSS patients is not difficult to implement.
It often requires the patient to take a supine position and an extended head posture to cooperate with the examination.
The equipment only needs a linear probe, and the parameters are generally 5-15 MHz, grayscale (B mode) or Doppler Le method for examination, this method can be used to examine the parotid and submandibular glands
.

However, the ultrasound diagnosis of pSS is now facing some doubts, mainly due to the sensitivity and specificity of concern, and the current lack of standards for ultrasound diagnosis of pSS
.

In addition, Professor Helen believes that ultrasound can be used to detect the disease activity and treatment response of pSS.
As for whether it can assess the risk of lymphoma, the professor is doubtful
.

In terms of future research directions, UHF ultrasound, Doppler ultrasound, contrast-enhanced ultrasound, and ultrasound ultramicrovascular imaging all have development prospects
.

In 2013, Professor Claudio Vitali, a Sjogren's syndrome researcher, believed that the salivary gland imaging technology at that time was outdated and supported ultrasound diagnosis as a supplementary item in the ACR-related guidelines
.

A Meta-analysis involving 6087 patients also studied the accuracy of pSS ultrasound diagnosis [4].
The study found that salivary gland ultrasound (SGUS) has diagnostic value for SS and can be used as an important criterion for pSS diagnosis
.

In promoting the application of ultrasound to pSS diagnosis, Jousse-Joulin S’s team has contributed a lot of work
.

As early as in a 2016 paper, the author believed that ultrasound is a very valuable tool for detecting salivary gland abnormalities in patients with pSS, but the reliability has not been studied [5]
.

In another study, his team then compared the 2016 ACR/EULAR pSS diagnostic criteria with the combined SUGS and found that the combined SGUS diagnostic criteria (0.
96, 0.
95-0.
98) were slightly better than the 2016 ACR/EULAR criteria (0.
95, 0.
93-0.
96), the ROC curve is shown in Figure 3 [6]
.

Figure 3.
ROC curves of different diagnostic standards.
After the continuous promotion of many researchers, people have found that even the use of B-mode ultrasound has the disadvantage of strong heterogeneity in the examination results, and there are relatively few studies on Doppler ultrasound
.

Until today, the diagnostic reliability data of ultrasound application in pSS is also very limited, so this still needs more research to move it forward
.

In addition, some studies have also seen the use of ultrasound for pSS disease and clinical research outcome monitoring, all of which add weight to the role of ultrasound in the diagnosis and treatment of pSS [7-8]
.

However, based on reality, gland biopsy is still the gold standard for diagnosing pSS.
Routine SGUS cannot rule out some salivary gland diseases.
Can other ultrasound methods have the power? Looking at the following research conclusions, you may have your own judgment: UHF ultrasound can recognize patients with negative biopsy[9]; microvascular imaging has higher sensitivity and specificity than Doppler ultrasound, and can be combined with clinical, Laboratory diagnosis and other imaging techniques are used as the diagnosis method of pSS [10]; multi-modal ultrasound can be used for pSS disease activity monitoring [11]; in the case where biopsy cannot be performed, salivary gland elastography can replace the diagnosis of pSS [12]; Artificial intelligence may assist in the diagnosis of SGUS and increase the diagnostic value of SGUS in pSS [13]
.

Summary: Ultrasound can indeed be used as a diagnostic method for examining the parotid and submandibular glands of patients.
It has similar specificity and sensitivity after combining with the 2016 ACR/EULAR diagnostic criteria
.

Whether Doppler ultrasound can be used as an alternative is currently unknown, and the value of ultrasound in pSS disease monitoring and prognostic evaluation needs further research to confirm
.

At present, in clinical practice and experimental observation, ultra-high frequency ultrasound, contrast-enhanced ultrasound, ultrasound ultra-microvascular imaging, and ultrasound elastography have been used as specific methods, and the value needs to be supported by more evidence
.

Experts comment that Sjogren’s syndrome (SS) is a systemic autoimmune disease with dry mouth and dry eyes as the main clinical manifestations.
Salivary glands are often the earliest organs involved.

.

Since the subjective symptoms of dry mouth and eyes are often not specific, the diagnosis needs to provide evidence of objective glandular lesions
.

Routine examinations include parotid angiography, salivary gland imaging, and labial gland biopsy, but such examinations are radiation or traumatic and are not easily accepted by patients
.

SGUS has the characteristics of non-invasive, non-radiation, and convenient operation.
In recent years, it has been increasingly used in the assessment of salivary gland diseases
.

A recent Meta analysis of 6087 pSS patients in 54 studies evaluated the diagnostic value of ultrasound for pSS
.

The study found that SGUS has a comprehensive sensitivity of 80% (95% CI: 77%-83%) and a specificity of 90% (95% CI: 87%-92%)
.

Another study found that on the basis of the 2016 ACR/EULAR classification standard, the combination of SGUS can further improve the sensitivity of the standard, which confirms that SGUS can be used as an important reference standard for pSS diagnosis
.

The existing gray-scale and Doppler ultrasound have insufficient evidence for the monitoring and prognostic evaluation of pSS.
New technologies such as ultra-high frequency ultrasound, contrast-enhanced ultrasound, ultrasound ultra-microvascular imaging, artificial intelligence, etc.
all need to be further developed and tested Research, has certain prospects in the future auxiliary pSS diagnosis and treatment
.

Expert Profile, Associate Professor Geng Yan, Department of Rheumatology and Immunology, Peking University First Hospital, Associate Chief Physician, Associate Professor, Youth Member and Secretary of the Chinese Medical Association Rheumatology Branch, Member of the Rheumatology Imaging Group of the Cross-Strait Medical and Health Exchange Association, Chinese Medical Doctor Association Rheumatology and Immunology Physician Branch Image Member and Secretary EULAR Certified International Musculoskeletal Ultrasound Trainer Reference: [1]Qin B,Wang J,Yang Z,et al.
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Imaging in Primary Sjgren's Syndrome[J].
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Diagnostic accuracy of salivary gland ultrasound in Sjgren's syndrome:A systematic review and meta-analysis[J].
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Is salivary gland ultrasonography a useful tool in Sjgren's syndrome? A systematic review.
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[9 ]Ferro F,Izzetti R,Vitali S,et al.
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