Background/Purpose: Ocular and oral dryness, occurring in isolation, represent distinct phenotypic subsets within Sjögren’s disease (SjD). However, potential differences in glandular imaging findings and pathophysiological mechanisms have not yet been adequately investigated. This study investigates how isolated ocular, isolated oral, and combined dryness phenotypes in SjD differ with respect to ultrasonographic patterns, histological findings, functional test outcomes, and patient-reported metrics

Methods: We retrospectively reviewed patients diagnosed with SjD based on the 2016 EULAR/ACR criteria from January 2017 to December 2024. All participants underwent labial gland biopsies and comprehensive imaging using high-frequency ultrasonography: 18 MHz for major salivary glands (SGUS), 48 MHz for lacrimal glands (LGUHFUS), and 70 MHz for labial salivary glands (LSGUHFUS). A semiquantitative OMERACT score (0–3) was used to define abnormal imaging (score ≥2). Patient-reported outcome (PRO) included the ESSPRI, OSDI, OHIP, and VAS scores for oral and ocular dryness. Dryness was categorized into four groups based on VAS scores: no dryness (VAS ocular< 5, VAS oral < 5), isolated ocular dryness (VAS ocular ≥5, VAS oral < 5), isolated oral dryness, (VAS ocular< 5, VAS oral ≥5) and double dryness (VAS ocular≥5, VAS oral≥5). In addition, patients presenting with either ocular dryness or oral dryness were analyzed separately. Systemic disease activity was evaluated using the ESSDAI score while functional assessment included unstimulated salivary flow rate (USWR) and the Schirmer’s test

Results: Among 191 SjD patients (mean age 55.3 ± 1.9 years; 8.4% male), 22 had no dryness, 32 isolated ocular, 24 isolated oral, and 113 both symptoms. PROs scores followed a gradient, with the double dryness group reporting the highest symptom burden, the no dryness group the lowest, and the isolated dryness groups falling in between (see Fig.1). Quality of Life (QoL) scores were higher in the no dryness group. Patients with isolated ocular dryness exhibited lower Schirmer’s test values compared to those with no dryness and isolated oral dryness (5.6±2.0 vs 12.2±3.5 and 6.2±2.4 respectively), but higher than double dryness (5.0±0.8, p< 0.001). Similarly, patients with isolated oral dryness had lower USWR than those with no dryness or isolated ocular dryness (2.9±1.5 vs 3.5±1.7 and 3.7±1.1 respectively), but higher than patients with double dryness (1.8±0.4) (Tab.1). No significant differences were observed in labial salivary gland histology or in the ultrasonographic findings of the lacrimal, labial, and major salivary glands. Finally, ESSDAI scores were lower in isolated ocular (2.8±1.1) and oral dryness (3.9±1.4) compared to no dryness (4.7±1.2) or double dryness (5.6±1.1)

Conclusion: In SjD isolated ocular and oral dryness are linked to specific functional deficits in the lacrimal and salivary glands, respectively. However, these isolated forms do not exhibit significant differences in histological features or glandular ultrasonographic findings. Clinically, isolated dryness appears to define a milder and distinct phenotype of SjD, marked by limited systemic involvement and a moderate burden on patient-reported outcomes

Figure 1 – Comparative Analysis of Patient-Reported Outcomes Across Dryness Phenotypes in Sjögren’s Syndrome

This radar chart illustrates the differences in various patient-reported outcomes including quality of life (QoL), Oral Health Impact Profile (OHIP), EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and Visual Analogue Scale (VAS) assessments for ocular and oral dryness, total dryness, pain, and fatigue. Each colour represents a different group: no dryness (blue), isolated ocular dryness (red), isolated oral dryness (orange), and double dryness (green), highlighting their respective impacts on the dimensions assessed.

Table 1 – Demographic and Clinical Characteristics of Sjögren’s Syndrome Patients by Dryness Phenotype

This table presents a comprehensive comparison of demographic and clinical parameters among Sjögren’s syndrome patients categorized into no dryness, isolated ocular dryness, isolated oral dryness, double dryness, and combined isolated ocular or oral dryness groups. Key parameters include age, gender distribution, Ocular Surface Disease Index (OSDI), unstimulated salivary flow rate (USWR), Schirmer’s test scores, Focus Score, Ectopic Lymphoid Structures (ELS), Major Salivary Gland Ultrasonography (SGUS), Lacrimal Gland Ultrasonography (LGUHFUS), labial salivary glands (LSGUHFUS) and EULAR Sjögren’s syndrome disease activity index (ESSDAI).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterizing-isolated-dryness-phenotypes-in-sjogrens-syndrome/