Primary Sjögren’s Syndrome: Current Pathophysiological, Diagnostic and Therapeutic Advances

Sjogren’s syndrome (SS) is a chronic autoimmune disease characterized by the lymphocytic infiltration of exocrine glands, mainly the salivary and lachrymal glands entailing the classical sicca syndrome of xerostomia (Sjögren, 1933) and xeropthalmia. Lymphocytic infiltration of other organs results in systemic manifestations. SS is classified as either primary (pSS), when occurring alone, or secondary (sSS), when occurring in addition to other autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus or myositis. As one of the most frequent autoimmune disease, affecting approximately 0.5% of the world population, SS is often associated with other diseases such as Hashimoto thyroiditis, coeliac disease, Biermer’s disease or systemic sclerosis. SS evolves as a slow, insidious disease affecting predominantly middle-aged women (female to male ratio of 9:1), SS lies at the cross roads of autoimmune diseases characterized by both cellular and humoral abnormalities. The disease typically affects middle-aged women around their fourth and fifth decades with extremes ranging from to 2 to 83 years. The morbidity of patients suffering from SS is incapacitating ranging from severe fatigue to evolving arthralgia. Even if the patients suffering from SS have a mortality rate comparable to the general population, they present an increased risk of developing lymphoma. The diagnosis of SS is based upon defined criteria according to the American-European consensus encompassing subjective and objective clinical signs and symptoms as well as immunological alterations. The pathogenesis of SS is complex and involves many components taking part in the autoimmune destruction of exocrine glands: proinflammatory cytokines secretion, apoptosis, matrix metalloproteases upregulation, autoantibody formation, as well as T and B cell proliferation. In SS, the classical histological findings in exocrine glands comprise focal inflammatory infiltrates, cell destruction and fibrosis in later stages of the disease. So far, SS treatment has been mainly symptomatic, consisting in relieving the clinical signs. However, recent pathophysiological findings have led to the development of new treatments.