impact factor, citescore

Full Papers


Glandular involvement in primary Sjögren’s syndrome patients with interstitial lung disease-onset and sicca-onset, a single centre cross-sectional study

1, 2, 3, 4, 5, 6, 7, 8, 9


  1. Rheumatology Unit, University of Pisa, Italy.
  2. Rheumatology Unit, University of Pisa, Italy.
  3. Division of Diagnostic and Interventional Radiology, Department of Translational Research and New Surgical and Medical Technologies, University Hospital of Pisa, Italy.
  4. Rheumatology Unit, University of Pisa, Italy.
  5. Rheumatology Unit, University of Pisa, Italy.
  6. Pathological Anatomy Unit, University Hospital of Pisa, Italy.
  7. Department of Diagnostic Imaging, 2nd Radiology Unit, University Hospital of Pisa, Italy.
  8. Rheumatology Unit, University of Pisa, Italy.
  9. Rheumatology Unit, University of Pisa, Italy.

2022 Vol.40, N°12
PI 2344, PF 2349
Full Papers

Free to view
(click on article PDF icon to read the article)

PMID: 36533977 [PubMed]

Received: 25/06/2022
Accepted : 15/09/2022
In Press: 30/11/2022
Published: 20/12/2022


Primary Sjögren’s syndrome (pSS) is an autoimmune exocrinopathy classically presenting with sicca symptoms. Nonetheless, disease onset with extraglandular manifestations, including interstitial lung disease (ILD), is increasingly reported. However, studies investigating pSS patients presenting with ILD (pSS-ILD) are limited. Aim of this study was to better characterise the phenotype of pSS patients presenting with ILD in comparison to pSS patients with classic sicca-onset. We especially investigated whether the two groups differed in glandular involvement comparing functional, imaging and histologic findings, as well as patient reported outcome (PRO).
Consecutive newly diagnosed pSS patients, all fulfilling the ACR/EULAR 2016 criteria, were included in this cross-sectional study from September 2016 to October 2021. Presence of ILD at pSS diagnosis was defined based on clinical findings, imaging assessment and pulmonary function tests (PFT). In addition to functional tests, a minor salivary gland biopsy was performed in all cases, recording number of foci, focus score (FS) and GC-like structures. Salivary glands ultrasonography (SGUS) was graded using the OMERACT semiquantitative scoring system (0-3) based on parenchyma inhomogeneity. PRO including ESSPRI, OHIP and OSSDI were collected. Extraglandular clinical features and biological abnormalities included in the ESSDAI were recorded. Data were expressed as mean±SD for continuous variables and as absolute frequencies and percentages for categorical variables. Chi-Square test and Mann-Whitney U-test and ANOVA were performed for comparisons of categorical variables and continuous variables, respectively.
We included 178 newly diagnosed pSS patients (F:M=158:20). ILD was the first pSS manifestation in 11 (6%) cases, 8 F and 3 M, with a median time from ILD onset to pSS diagnosis of 2 years (25-75 IQ 1-4.5). Of the 11 pSS-ILD patients, HRCT pattern was defined as NSIP in 4, UIP in 4, NSIP+OP in 2 and LIP in 1 patient. Dyspnoea on exertion or chronic cough were reported by 7/11 (63.6%) patients. In comparison to sicca-onset patients, pSS-ILD patients presented an older age at diagnosis (55±13 vs. 70±7, p= 0.001) and a higher ESSDAI (3.9±4.7 vs. 12.3±4.3, p=0.001), driven by the pulmonary domain. Regarding glandular involvement, pSS-ILD patients reported milder xeropthalmia (VAS 5.8±3.1 vs. 2.8±3.5, p=0.002) and significative lower scores in OSDI (35.6±24.9 vs. 15.3±22.9, p=0.04) and OHIP (4.8±4.4 vs. 1.4±3.8, p=0.04), despite no significant differences observed between the two groups in ocular tests and unstimulated salivary flow rate. With respect to histology, no significant differences were found in number of foci, FS and GC-like structures. We observed a significantly different distribution of the SGUS OMERACT score in the two groups: none of pSS-ILD patients presented a SGUS OMERACT score ≥2 in the submandibular glands (SG), in contrast to 41/132 (31.1%) of the patients in the classical sicca-onset group (p=0.03). Finally, no significant differences were observed between the two groups with respect to non-pulmonary extraglandular manifestations, serologic features and other biological parameters.
ILD-onset pSS patients represent an atypical phenotypic subset, with less pronounced sialadenitis structural changes in salivary glands, and with sicca symptoms probably overshadowed by the respiratory disease.


Rheumatology Article