Sjögren syndrome: looking forward to the future

Abstract

Primary Sjögren's syndrome (pSS) is a heterogeneous disease characterised by a wide spectrum of manifestations that vary according to the different stages of the disease and among different subsets of patients. The aim of this qualitative literature review is to summarise the recent advances that have been reported in pSS, ranging from the early phases to the established disease and its complications. We analysed the diagnostic, prognostic, and management aspects of pSS, with a look into future clinical and research developments. The early phases of pSS, usually antedating diagnosis, allow us to investigate the pathophysiology and risk factors of the overt disease, thus allowing better and timely patient stratification. Salivary gland ultrasound (SGUS) is emerging as a valid complementary, or even alternative, tool for histopathology in the diagnosis of pSS, due to a standardised scoring system with good agreement and performance. Other promising innovations include the application of artificial intelligence to SGUS, ultrasound-guided core needle biopsy, and a wide array of novel diagnostic and prognostic biomarkers. Stratifying pSS patients through the integration of clinical, laboratory, imaging, and histopathological data; differentiating between activity-related and damage-related manifestations; and identifying patients at higher risk of lymphoma development are essential steps for an optimal management and individualised treatment approach. As new treatment options are emerging for both glandular and systemic manifestations, there is a need for a more reliable treatment response evaluation. pSS is a complex and heterogeneous disease, and many distinct aspects should be considered in the different stages of the disease and subsets of patients. In recent years, efforts have been made to improve our understanding of the disease, and certainly in the coming years, some of these novelties will become part of our routine clinical practice, thus improving the management of pSS patients.

Keywords: Sjögren’s syndrome; activity; biomarkers; damage; histopathology; lymphoma; pathogenesis; preclinical phase; salivary gland; treatment; ultrasonography.

Figure 1.

Outcome Measures in Rheumatology Clinical Trials (OMERACT) four-grade semiquantitative scoring system for major salivary gland lesions in primary Sjögren’s syndrome. Ultrasound images of the parotid gland in a four-grade semiquantitative scoring system by OMERACT: (a) grade 0, normal parenchyma; (b) grade 1, minimal change: mild inhomogeneity without anechoic/hypoechoic areas; (c) grade 2, moderate change: moderate inhomogeneity with focal anechoic/hypoechoic areas but surrounded with normal tissue; and (d) grade 3, severe change: diffuse inhomogeneity with anechoic/hypoechoic areas occupying the entire gland surface but surrounded with no normal tissue.

Figure 2.

Ultrasound images of healthy and pathological salivary glands (SGs): (a) parotid gland of healthy subject with homogeneous parenchyma; (b) parotid gland of a primary Sjögren’s syndrome (pSS) patient, the gland is atrophic, an intraparenchymal lymph node is present (*); (c) parotid gland of a pSS patient with inhomogeneous parenchyma due to the presence of hypoechoic lesions, described as pseudocystic lesions (void arrows), and hyperechoic bands (white arrows); and (d) parotid gland of a pSS patient with inhomogeneous parenchyma, with multiple calcifications present.

Figure 3.

Ultrasound-guided core needle biopsy (CNB) of the major salivary glands in primary Sjögren’s syndrome (pSS) patients with suspected salivary gland lymphoma: (a) pSS patient with swollen left parotid gland; (b) pSS patient undergoing ultrasound-guided CNB of the left submandibular gland; (c) ultrasound image of the parotid gland with focal lesion suspected of lymphoma; and (d) ultrasound image of the parotid gland showing inhomogeneous parenchyma suspected of lymphoma in the absence of focal lesion. The needle is indicated by white arrows (d).