Sjogren Syndrome

Overview
  • Sjogren Syndrome is a chronic autoimmune disease primarily of women in which exocrine glands are targeted, leading to a characteristic symptomology of dry eyes and dry mouth. Although it can exist as an isolated syndrome, Sjogren's often develop in the context of other systemic autoimmune disorders.
Pathogenesis
  • Sjogren Syndrome appears to arise from hyperactivity of both the cellular and humoral immune response. Consequently, it is characterized by a lymphocytic destruction of exocrine glands, mediated by T-cells, as well as production of auto-antibodies by B-cells. There are no highly specific auto-antibodies diagnostic for Sjogren's; however, patients typically display ANAs, antibodies to rheumatoid factor as well as the slightly more specific antibodies to SS-A (Anti-Ro) and SS-b (Anti-La). In addition to auto-antibodies, many patients will display hypergammaglobulinemia, a product of simply excessive polyclonal antibody production by plasma cells.
Morphology
  • The exocrine tissues most commonly targeted for autoimmune destruction are the lacrimal and salivary glands although those of the upper respiratory tract mucosa may be involved as well. Affected tissues display an intense lymphocytic infiltrate dominated by CD4+ T-cells although B-cells and plasma cells are also present. In some cases, the inflammatory infiltrate will begin to organize into lymphoid-like architecture with germinal centers.
Clinical Consequences
  • Overview
    • Sjogren Syndrome is largely a disease of women who account for over 90% of patients, with typical onset in adulthood. The clinical consequences of the disease largely revolve around reduced lacrimal and salivary exocrine function. In a subset of patients the disease may evolve to include extra-glandular sites or alternatively Sjogren's may arise within the context of a systemic autoimmune disease. Whatever the case, the disease typically develops insidiously and charts a slow, progressive course.
  • Glandular Symptoms
    • Progressive loss of salivary secretion initially presents as xerostomia (dry mouth) which over time yields a propensity for dental carries and may ultimately result in ulceration of the oral mucosa. Inflammation of the salivary glands frequently results in their enlargement, especially the parotid glands
    • Progressive loss of lacrimation initially leads to a sensation of dry, gritty eyes but over time can have serious consequences, including inflammatory destruction and ulceration of the corneal epithelium, termed keratoconjunctivitis sicca.
  • Extra-glandular Symptoms
    • A minority of patients will develop systemic disease that may involve a number of organs. Alternatively, Sjogren's may be accompanied by another defined autoimmune disorder, the most common being Rheumatoid Arthritis. Interestingly, long-term presence of Sjogren Syndrome dramatically increases the risk of developing Non-Hodgkin Lymphoma, especially of the MALT Lymphoma subtype, likely a consequence of chronic inappropriate B-cell activation.