Whether Quantitative Stimulation Test with Dynamic Salivary Gland Scintigraphy Could be Re-included in New Sjogren's Syndrome Classification Criteria

Objectives: Sjögren’s syndrome (SS) is a multisystem inflammatory autoimmune disease, characterized by lymphocytic infiltration of the exocrine glands and epithelia in multiple sites, in particular, results in hypofunction of salivary and lacrimal glands [1]. Although the salivary scintigraphy has been complained of low specificity for diagnosis of SS [2,3], an abnormal result of salivary scintigraphy was accepted by the 2002 AECG criteria [4], Japanese criteria (1999) or former versions as a diagnostic criteria item. Nevertheless, it was being omitted by 2012 ACR criteria[3] and recent 2016 ACR/ EULAR criteria [5]. In all of the criteria accepted salivary scintigraphy as a criteria item for SS, the standard interpretation of salivary scintigraphy positivity results was proposed by Schall [6]. It is worth noting that their work was published in 1971, and there were some shortcomings of the Schall’s categorical classification. Conversely, in present study, we developed a new quantitative stimulation test with dynamic salivary glands scintigraphy (qsDSGS) for assessing the function of salivary glands for SS, and its advantages included: stimulation intervention test with sequential dynamic salivary glands scintigraphy, semi-quantitative analysis, modern SPECT/CT systems equipped with total digital high-definition SPECT detector technology, reliable and reproducible image processing software technology [7]. Although some high-level papers about salivary scintigraphy for SS have been published [8-10], the method and scintigraphy data quantitative analysis for SS still remain not to be well established. In this study, we aimed to develop a new qsDSGS analysis method for identifying and better grading of salivary glands dysfunction, and assessing its diagnostic efficacy.

Methods: Over a two year period, the results of histopathology, oral examination, ocular examination, serological examination and pertechnetate qsDSGS of 268 consecutive patients (male/female ratio 28/240, mean age 56 yrs, S.D. 13, range 23-86 yrs) with clinically suspicious SS were evaluated. The serological examination included the autoantibodies against nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-70, PM-Scl, Jo-1, centromere protein B, PCNA, dsDNA, nucleosomes, histones, ribosomal P-proteins, AMA M2, rheumatoid factor, RA-specific autoantibodies against cyclic citrullinated peptides, ANA, ANA tite and so on. The final diagnosis was based on the 2016 ACR/ EULAR criteria. RESULTS Based on quantitative analysis from qsDSGS, ROC analysis for the PUL (peak uptake level) (91 pSS, 67 sSS, 33 non-SS) and the sEF (stimulation ejection fraction) (35 pSS, 22 sSS, 20 non-SS), the threshold of PUL ≤10 cps/pixel (counts per second /pixel/MBq) as positivity, it could provide better diagnostic value with 88.4% specificity and 71.3% sensitivity (LR 6.15) for SS and grouped into Class 3; the optimal cutoff of sEF was 54%. All patients can be classified into 4 Class groups by qsDSGS: Class 1 (normal; n=44), Class 2 (mild to moderate involvement; n=130), Class 3 (severe involvement; n=56) and Class 4 (non function; n=38).

Conclusions: We developed a brand-new qsDSGS for assessing the salivary glands function, which features can promote it re-included in the new SS classification criteria as a suitable alternative criteria item instead of former salivary scintigraphy. The diagnostic performance of qsDSGS is higher than ultrasound in detecting SS, and the qsDSGS should become a part of clinical common practice for the purpose of clinical research and management of SS to support physicians’ diagnostic confidence in the future. Research Support: none