Sjögren Syndrome

Sjögren syndrome is a systemic autoimmune disease characterized by chronic lymphocytic infiltration of the exocrine glands, particularly the lacrimal and salivary glands, leading to dryness of the eyes and mouth (sicca symptoms). Beyond the glands, it can involve the joints, skin, lungs, kidneys, and nervous system, and it carries an increased risk of B-cell lymphoma.

Definition

Sjögren syndrome is an autoimmune exocrinopathy defined by lymphocytic infiltration and dysfunction of the salivary and lacrimal glands, producing dry eyes and dry mouth, often accompanied by anti-Ro/SSA antibodies and systemic extraglandular features; it occurs as a primary disease or in association with another connective tissue disease.

Scope

This entry covers Sjögren syndrome as a clinical entity within the systemic autoimmune diseases: the immune-mediated injury to exocrine glands, the prototypical anti-Ro/SSA and anti-La/SSB autoantibodies, the spectrum of glandular and extraglandular involvement, the lymphoma association, and how classification criteria define study populations. It is reference-educational and does not provide diagnostic or treatment instructions.

Key concepts

• Sicca symptoms (dry eyes and dry mouth)
• Lymphocytic infiltration of exocrine glands
• Anti-Ro/SSA and anti-La/SSB antibodies
• Focal lymphocytic sialadenitis on biopsy
• Primary versus secondary (associated) Sjögren syndrome
• Extraglandular systemic involvement
• Risk of B-cell lymphoma

Mechanisms

In Sjögren syndrome, autoreactive lymphocytes infiltrate the lacrimal and salivary glands, producing focal lymphocytic sialadenitis and impairing secretory function. Epithelial cells are thought to participate actively in the immune response, a concept captured by the term autoimmune epithelitis, and a type I interferon signature and B-cell hyperactivity are characteristic. The anti-Ro/SSA and anti-La/SSB autoantibodies are serologic hallmarks, and chronic B-cell activation underlies both the systemic features and the elevated risk of B-cell non-Hodgkin lymphoma (Mariette & Criswell, 2018; Brito-Zerón et al., 2016).

Clinical relevance

Sjögren syndrome illustrates how organ-targeted autoimmunity (of exocrine glands) coexists with systemic features and a defined malignancy risk. It may occur on its own or alongside another connective tissue disease such as lupus or rheumatoid arthritis. The 2016 ACR/EULAR classification criteria define consistent research populations rather than diagnose individuals (Shiboski et al., 2017). This entry describes the disease conceptually and is not a basis for individual diagnostic or therapeutic decisions.

Epidemiology

Sjögren syndrome shows a strong female predominance and typically presents in middle age, although it can occur earlier. It is one of the more common systemic autoimmune diseases, and the lifetime risk of B-cell lymphoma is increased relative to the general population (Mariette & Criswell, 2018; Brito-Zerón et al., 2016).

Evidence & guidelines

Classification of primary Sjögren syndrome for research uses the 2016 ACR/EULAR criteria, which weight items including anti-Ro/SSA antibody status, labial salivary gland biopsy with focal lymphocytic sialadenitis, and objective measures of ocular and oral dryness (Shiboski et al., 2017). These criteria standardize study populations and are distinct from clinical diagnosis.

History

Henrik Sjögren's 1933 description of keratoconjunctivitis sicca with associated systemic features defined the syndrome that bears his name. The later identification of anti-Ro/SSA and anti-La/SSB antibodies and of characteristic salivary gland histopathology, followed by successive classification efforts culminating in the 2016 ACR/EULAR criteria, established the modern understanding of the disease.

Debates

How should primary Sjögren syndrome be classified and stratified?

Successive classification criteria have weighted serology, histopathology, and functional tests differently, and there is ongoing discussion about how best to stratify patients by systemic activity and lymphoma risk for research and trials.

Key figures

• Xavier Mariette
• Manuel Ramos-Casals
• Pilar Brito-Zerón

Seminal works

• mariette-2018
• brito-zeron-2016
• shiboski-2017

Frequently asked questions

What is the difference between primary and secondary Sjögren syndrome?

Primary Sjögren syndrome occurs on its own, whereas secondary (or associated) Sjögren syndrome arises in the context of another connective tissue disease such as systemic lupus erythematosus or rheumatoid arthritis.

Why is Sjögren syndrome linked to lymphoma?

Chronic B-cell activation that drives the autoimmune response is also associated with an increased risk of B-cell non-Hodgkin lymphoma, making this a recognized long-term concern in the disease.