Excerpt from Sjogren Syndrome

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Background

Sjögren syndrome (SS) is an autoimmune disorder characterized by salivary and lacrimal gland dysfunction, resulting in keratoconjunctivitis sicca (KCS) and xerostomia (ie, dry mouth) as a result of immune lymphocytes that infiltrate these secretory glands. Nasal and vaginal mucous membranes are also commonly affected. Other systemic manifestations, most commonly rheumatoid arthritis and systemic lupus erythematosus, can be associated. Although several reports of this condition were documented in the late 1800s, Henrik Sjögren, a Swedish ophthalmologist, described the clinical and pathological findings of this syndrome affecting menopausal women in a classic monograph in 1933.

Sjögren syndrome may occur alone (primary) or in conjunction with other autoimmune diseases (secondary). Primary Sjögren syndrome has 2 subsets: patients with systemic immune dysfunction but no defined connective tissue dysfunction, and patients who lack evidence of systemic immune dysfunction or defined connective tissue disease. Secondary Sjögren syndrome occurs in patients who have defined connective tissue disease. The most commonly associated connective tissue diseases are rheumatoid arthritis and systemic lupus erythematosus, but Sjögren syndrome has also been reported in conjunction with progressive systemic sclerosis, Hashimoto thyroiditis, polymyositis, polyarteritis nodosa, and Waldenström macroglobulinemia.

Pathophysiology

The pathogenesis of Sjögren syndrome has not been fully elucidated, but the central role of glandular epithelial cells has been identified as key to understanding the disease. An environmental stimulus (eg, viral infection) is believed to trigger inappropriate apoptosis of glandular epithelial cells, producing autoantigens that trigger lymphocytic infiltration of the secretory glands with subsequent production of autoantibodies and cytokines. Dysfunction of residual glandular epithelial cells may also contribute to deficient tear production. Additionally, it has been demonstrated that there is a reduced rate of apoptosis among immune-stimulated lymphocytes, thus exacerbating the loss of glandular secretory function.

Studies have shown that CD4+ T lymphocytes play a key role in the pathogenesis of Sjögren syndrome. T cells have been demonstrated to induce apoptosis of epithelial cells by 3 mechanisms: Fas-FasL interaction, protease release, and cytokine production. FasL is expressed on activated T lymphocytes. Binding of activated T lymphocytes with ubiquitously expressed Fas antigen leads to apoptosis of susceptible epithelial cells.

Patients with Sjögren syndrome demonstrate an imbalance in cytokine production. In addition, in primary Sjögren syndrome, there is increased expression of IFN in the minor salivary glands. Studies have confirmed that primary Sjögren syndrome has a systemic expression, including extraglandular manifestations in the lungs (interstitial pneumonitis) and the kidneys (interstitial nephritis).

Sjögren syndrome is also characterized by increased B cell activity. An antigen-driven B cell response has been proposed to occur in the salivary glands of patients with Sjögren syndrome. Patients with Sjögren syndrome are at an increased risk of developing B cell non-Hodgkin lymphoma and other lymphoproliferative disorders. In fact, 5% of patients with primary Sjögren syndrome develop B cell non-Hodgkin lymphoma. This increased risk has been attributed to B cell hyperactivity and reduced natural killer cell activity.

Frequency

United States

The incidence has been estimated by the San Diego criteria as 0.5%.

International

The European study group estimates an incidence of 3-5%.

Mortality/Morbidity

Severe dry eyes can cause corneal scarring, ulceration, infection, and even perforation.

Sex

The female-to-male ratio is 9:1.

Age

Although primarily a disease of postmenopausal women, age can range from 22-70 years, with the average age being 43 years. There is often a delay of 5-10 years between disease onset and diagnosis.

Sjögren syndrome has also been reported in children who developed recurrent parotid gland enlargement.

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