Primary-Sjögren's-Syndrome-Related Interstitial Lung Disease: A Clinical Review Discussing Current Controversies

Abstract

Lung involvement, especially interstitial lung disease, is a potentially severe extra-glandular manifestation of Primary Sjogren's Syndrome (pSS-ILD). ILD can manifest either as a late complication of pSS or anticipate sicca symptoms, likely reflecting two different patho-physiological entities. Presence of lung involvement in pSS subjects can remain subclinical for a long time; therefore, patients should be actively screened, and lung ultrasound is currently being investigated as a potential low cost, radiation-free, easily repeatable screening tool for detection of ILD. In contrast, rheumatologic evaluation, serology testing, and minor salivary gland biopsy are crucial for the recognition of pSS in apparently idiopathic ILD patients. Whether the HRCT pattern influences prognosis and treatment response in pSS-ILD is not clear; a UIP pattern associated with a worse prognosis in some studies, but not in others. Many aspects of pSS-ILD, including its actual prevalence, association with specific clinical-serological characteristics, and prognosis, are still debated by the current literature, likely due to poor phenotypic stratification of patients in clinical studies. In the present review, we critically discuss these and other clinically relevant "hot topics" in pSS-ILD. More specifically, after a focused discussion, we compiled a list of questions regarding pSS-ILD that, in our opinion, are not easily answered by the available literature. We subsequently tried to formulate adequate answers on the basis of an extensive literature search and our clinical experience. At the same, we highlighted different issues that require further investigation.

Keywords: Sjögren’s; interstitial lung disease; lung ultrasound; patterns; prognosis; treatment.

Figure 1

A 68-year-old female pSS patient. Bilateral diffuse ground glass opacities, thickening of subpleural interstitial lobular septa, and traction bronchiectasis compatible with NSIP pattern.

Figure 2

UIP pattern with bilateral subpleural honeycombing and traction bronchiectasis in a 73-year-old male pSS patient.

Figure 3

Patchy opacities with peribronchovascular and subpleural distribution in a 64-year-old female pSS patient, suggestive of OP pattern.

Figure 4

HRCT scan of a 42-year-old female pSS patient in 2008 (A) showing only very modest signs of bronchiolitis. She went on to experience recurrent episodes of acute dyspnea and cough, and follow-up HRCT scans in 2011 (B) and 2021 (C) document progressive formation of thin-walled cysts. The combination of these imaging findings and appropriate clinical context in a pSS patient is virtually pathognomonic of LIP. Of note, confluence of LIP cystic lesions into larger ones (as is shown in (C)) exposes the patient to higher risk of complications.

Figure 5

(A) HRCT scan of a patient with pSS showing bilateral subpleural honeycombing and traction bronchiectasis compatible with UIP pattern. (B) LUS performed on the same patient, with a 5–12 MHz linear probe showing marked irregularities of the pleural line.