Study links salivary gland swelling to distinct Sjögren’s profile

Swelling of the major salivary glands without dry mouth at the time of a Sjögren’s disease diagnosis may point to a distinct disease profile marked by younger age, higher disease activity, and more severe glandular abnormalities, a study from South Korea suggested.

“Recognition of this [Sjögren’s] presentation may support a more comprehensive baseline [initial] clinical and immunologic evaluation,” the researchers wrote.

The study, “Characteristic clinical and immunologic features of Sjögren’s disease patients presenting with major salivary gland swelling at diagnosis,” was published in Clinical Rheumatology.

Sjögren’s is caused by self-reactive antibodies that primarily attack the glands that produce tears and saliva. While dry eyes and mouth are hallmark Sjögren’s symptoms, the disease can affect several other parts of the body.

In routine clinical practice, “the presenting symptom may influence the extent of baseline glandular imaging, immunologic assessment, and subsequent clinical monitoring performed at the time of diagnosis,” the researchers wrote.

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Looking for clues to disease profile

Major salivary gland swelling is a well-recognized Sjögren’s feature that has been linked to active glandular inflammation and excess activity of B-cells, the immune cells that produce antibodies, including those driving Sjögren’s. However, whether major salivary gland swelling without dry mouth at diagnosis identifies a distinct clinical profile of Sjögren’s remains unclear.

To learn more, four researchers in South Korea retrospectively analyzed data from 731 people diagnosed with Sjögren’s at a hospital in Seoul between 2020 and 2025. At diagnosis, 48.3% were experiencing dryness (sicca) symptoms, while the remaining 51.7% presented non-sicca manifestations.

Among non-sicca manifestations, major salivary gland swelling was the initial presenting symptom in 48 patients (6.6% of all participants). The most common non-sicca manifestations were the presence of self-reactive antibodies (16.7%) and joint pain (15%).

The team then compared features of people with major salivary gland swelling at diagnosis with those with other initial symptoms. They found that patients with glandular swelling were significantly younger than those with other initial symptoms (median age 26 vs. 52).

The glandular swelling group also had higher objective body-wide disease activity, as reflected by significantly higher scores in the validated EULAR Sjögren’s disease activity index (ESSDAI) and physician global assessments.

Despite this, patient-perceived symptom burden, as assessed with the validated EULAR Sjögren’s Syndrome Patient-Reported Index and patient global assessment, did not differ significantly between the two groups.

This suggests that participants with glandular swelling at diagnosis may have more active underlying disease than their symptoms alone would indicate, the team noted.

“Salivary gland functional tests showed modest and partly discordant differences between groups,” the researchers wrote.

In contrast, people with glandular swelling showed more severe abnormalities on salivary gland ultrasound (SGUS) and significantly higher SGUS scores, reflecting more structural tissue changes and inflammation. This indicates that imaging may better capture the glandular changes associated with swelling than measures of glandular function, the researchers noted.

Among participants with available data on manifestations affecting tissues other than glands, those with glandular swelling were significantly less likely to have joint pain or inflammation than those without glandular swelling (8.9% vs. 22.2%). Those with glandular swelling were significantly more likely to have enlarged lymph nodes, immune structures located throughout the body (26.7% vs. 15.2%).

Glandular swelling presenters were also significantly more likely to have abnormally high blood levels of antibodies (66% vs. 45.8%) and low blood levels of the immune C3 protein, which suggests body-wide immune activation and inflammation (39.6% vs. 22.1%).

Statistical analyses adjusted for potential influencing factors showed that younger age at diagnosis and low C3 levels remained independently associated with major salivary gland swelling at diagnosis. Higher SGUS scores also showed a trend toward an association, although without statistical significance.

Overall, the findings suggest that patients with major salivary gland swelling but no sicca symptoms may represent a distinct clinical and immunologic profile of Sjögren’s, characterized particularly by younger age at diagnosis, low C3 levels, and more pronounced salivary gland abnormalities on imaging.

“These findings emphasize the clinical importance of symptom-based diagnostic entry points and support the recognition of major salivary gland swelling as a meaningful early [form of Sjögren’s disease],” the researchers wrote.

They emphasized, however, that the findings should be interpreted with caution because of the limited number of patients with glandular swelling at diagnosis.

Multicenter studies following patients over time “are needed to validate glandular swelling as an early disease [profile] and to assess its prognostic implications,” the team wrote. “Integration of molecular and imaging biomarkers may further refine this [profile] and inform personalized management strategies.”