"The earliest histologic finding in both the major and the minor salivary glands is periductal and perivascular lymphocytic infiltration." (Ref: Robbins) Sjogren SyndromeIt is an immune-mediated destruction of the lacrimal and salivary glands characterized by dry eyes {keratoconjunctivitis sicca) and dry mouth (xerostomia) It occurs as an isolated disorder (primary form), also known as the sicca syndrome, or more often in association with another autoimmune disease (secondary form). Associated diseases Rheumatoid Arthritis (Me) SLE Polymyositis Systemic sclerosis Vasculitis Thyroiditis The ductal epithelial cells of the exocrine glands are the primary target for autoantibodies. There is also systemic B-cell hyperactivity, as evidenced by the presence of ANAs and RF. Autoantibodies to the RNP antigens SS-A (Ro) and SS-B (La) (also present in SLE) Other secretory glands like nasopharynx, upper airway, and vagina, may also be involved Involved tissues show an intense lymphocyte (primarily activated CD4+ T cells) and plasma cell infiltrate. Lacrimal gland destruction results in a lack of tears, leading to drying of the corneal epithelium, with subsequent inflammation, erosion, and ulceration (keratoconjunctivitis). Similar changes may occur in the oral mucosa as a result of the loss of salivary gland output, giving rise to mucosal atrophy, with inflammatory Assuring and ulceration (xerostomia). Dryness and crusting of the nose may lead to ulcerations and even perforation of the nasal septum. When the respiratory passages are involved, secondary laryngitis, bronchitis, and pneumonitis may appear. Approximately 25% of the patients (especially those with anti-SS-A antibodies) develop extra-glandular disease affecting the CNS, skin, kidneys, and muscles. Renal lesions take the form of mild interstitial nephritis associated with tubular transport defects: Unlike in SLE. glomerulonephritis is rare. 90% of cases occur in women between 35 and 45 years Extraglandular manifestations include synovitis, pulmonary fibrosis, and peripheral neuropathy. There is a 40-fold increased risk of developing non-Hodgkin B-cell lymphoma.