A non-invasive assessment of salivary gland damage by ultrasound may be added to current criteria for primary Sjögren’s syndrome (pSS) diagnosis without lowering their accuracy, according to a large clinical practice study.
The inexpensive assessment may replace invasive tests that are unavailable in some centers, which improves the feasibility of the ultrasound test and reduces the number of required salivary gland biopsies, the scientists suggested.
Their research, “Incorporation of salivary gland ultrasonography into the ACR-EULAR criteria for primary Sjögren’s syndrome,” appeared in the journal Arthritis Care & Research.
The recently developed American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria have shown high sensitivity and specificity in the classification of pSS. Among other features, the criteria include disease-related changes in the salivary glands, having anti-SSA antibodies, tear gland involvement — as assessed by the Schirmer’s test — and ocular surface damage. However, a test measuring salivary gland damage is still lacking.
Salivary gland ultrasonography (SGUS) has been increasingly used to evaluate structural changes of the salivary glands in people with pSS. The method is inexpensive, is amenable for use in an outpatient setting, and has shown accuracy in identifying pSS cases, but its inclusion in the ACR-EULAR criteria has not been considered.
A team from the University of Groningen and University Medical Center Groningen, in The Netherlands, addressed this gap by testing whether adding SGUS or using it to replace current items in the ACR-EULAR criteria would improve pSS diagnosis.
A total of 243 participants were included, who were clinically suspected of having pSS or diagnosed with this disorder, and taking part in the ASAPIII Phase 3 trial (NCT02067910) or the RESULT observational study, both funded by Bristol-Myers Squibb.
Participants underwent SGUS between October 2014 and July 2017, with its average score for hypoechogenic areas — less dense than usual — determined in one parotid and one submandibular gland (under the chin and tongue). Patients underwent a labial gland biopsy (124), parotid gland biopsy (198) or both (79) up to seven months after SGUS.
The results showed that the accuracy of SGUS to predict clinical diagnosis was good, with an optimal cut-off value of at least 1.5. Of note, the maximum SGUS score is 3, which corresponds to having numerous hypoechogenic areas.
Using this threshold, SGUS was positive in 106 pSS and six non-pSS patients. The agreement with clinical diagnosis was 80.7%, sensitivity (the proportion of actual positives that were correctly identified as such) was 72.1%, and specificity (the proportion of actual negatives that correctly test negative) was 93.8%.
Then, the team found that the ACR-EULAR criteria best diagnosed pSS if SGUS was given 1 point in the overall score. Yet, the optimal ACR-EULAR cut-off point to identify pSS remained 4.
In patients who underwent a labial gland biopsy, adding SGUS resulted in a similar agreement with clinical diagnosis, slightly increased sensitivity (from 95.9% to 97.3%) and slightly decreased specificity, from 92.2% to 90.2%. Similar findings were obtained in the group undergoing parotid gland biopsy.
This shows that the “validity of the ACR–EULAR criteria remains high after incorporation of SGUS,” the team wrote. Incorporating SGUS into these criteria would allow rheumatologists to choose from a larger array of tests and reduce the number of needed salivary gland biopsies, the scientists added.
Subsequent analysis revealed that replacing salivary gland biopsy or the measurement of anti-SSA antibodies with SGUS markedly decreased the accuracy of the ACR-EULAR criteria.
In addition, using SGUS to replace the Ocular Staining Score of ocular damage, the Schirmer’s test or unstimulated whole saliva flow (a functional test of salivary gland involvement) led to minor changes. This suggests that centers with less access to these tests could replace them with SGUS, without compromising accuracy, the researchers said.