Sjögren's Syndrome at a Glance
- Chronic autoimmune disease characterized by chronic inflammation involving the exocrine glands.
- Salivary and lachrymal glands are predominantly affected leading to dry mouth and dry eyes.
- May occur alone (primary Sjögren's syndrome), or may coexist with other systemic connective tissue disorders (secondary Sjögren's syndrome).
- Systemic manifestations, such as fatigue, arthritis, vasculitis, interstitial pulmonary disease, peripheral or central neuropathy, and autonomic nervous dysfunction may accompany glandular involvement.
- Patients with systemic manifestations are at higher risk of lymphoma.
- Treatment of sicca symptoms is mainly symptomatic, whereas management of extraglandular manifestations is similar to other autoimmune diseases.
Sjögren's syndrome (SS) is one of the most common rheumatic autoimmune diseases. SS affects predominantly women with a female to male ratio of 9:1. Women are most commonly diagnosed in their fifth or sixth decade, but it can affect individuals of any age and sex.
SS has a worldwide distribution. In most studies done mainly in Caucasian populations the estimated prevalence rate in the adult general population is between 0.1% and 0.8%. However, one study in the United Kingdom showed a prevalence rate of 3.3%, whereas another study in Japan showed only a 0.02% prevalence rate. The estimated annual incidence rate was consistently approximately 0.005% in several studies.1
The pathogenesis of SS is still largely unknown. In a genetically predisposed individual, various environmental factors, such as viral infections, may lead to epithelial-cell activation and a protracted inflammatory response with features of autoimmunity. Autoreactive lymphocytes and autoantibodies are considered important in this process, although the pathogenic role of any particular autoantibody is still undefined. Abnormal apoptosis may be important in several ways. First, increased apoptosis of epithelial cells may lead to functional defects and provide autoantigens, whereas the prolonged survival of B and T cells through upregulation of antiapoptotic signals may be involved in sustaining a self-perpetuating autoimmune process. Decreased apoptosis of lymphocytes may also contribute to the increased frequency of lymphoma in SS patients.
The role of genetic factors in SS was recognized in family studies where first-degree relatives of patients had an increased prevalence of SS.2 Such family clustering was further observed among first-degree relatives of individuals with anti-Ro/SSA antibodies regardless of their clinical diagnoses (SS or systemic lupus erythematosus or even healthy controls).3
There is a well-established association between SS or anti-Ro/SSA and anti-La/SSB antibodies with HLA class II genes.4 Genes other than those of the HLA loci may also be associated with an increased risk of disease. Associations with a number of cytokine gene polymorphisms, such as interleukin (IL) 6, IL-10, tumor necrosis factor-α (TNF-α) and the IL-1 receptor antagonist, have been reported, but none of these have been confirmed to date.4 Several genetic polymorphisms previously linked to systemic lupus erythematosus and other autoimmune diseases are also associated with SS. From these, two transcription factors, (1) signal transducer ...