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Clinical manifestations of Sjögren's syndrome: Extraglandular disease

Alan N Baer, MD, FACP
Section Editor
Robert Fox, MD, PhD
Deputy Editor
Paul L Romain, MD


Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory disorder characterized by diminished lacrimal and salivary gland function, although the clinical manifestations of SS include both exocrine gland involvement and extraglandular disease features [1]. SS occurs in a primary form not associated with other diseases and a secondary form that complicates or overlaps other rheumatic conditions, most commonly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

In both primary and secondary SS, decreased exocrine gland function leads to a combination of dry eye (keratoconjunctivitis sicca) and dry mouth (xerostomia) symptoms [2,3]. In addition, a variety of other disease manifestations can occur that may affect a range of tissues involving most organ systems.

The extraglandular disease manifestations of SS will be reviewed here. The exocrine manifestations, diagnosis, treatment, and prognosis of both sicca and extraglandular manifestations are discussed separately. (See "Clinical manifestations of Sjögren's syndrome: Exocrine gland disease" and "Diagnosis and classification of Sjögren's syndrome" and "Treatment of dry eye in Sjögren's syndrome: General principles and initial therapy" and "Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren's syndrome" and "Overview of the management and prognosis of Sjögren's syndrome".)


The extraglandular manifestations of Sjögren’s syndrome (SS) arise from diverse pathogenetic mechanisms [4]. Some represent autoimmune-induced inflammation centered on ductal epithelial structures in various organs, such as the liver (eg, primary biliary cholangitis [PBC; previously referred to as primary biliary cirrhosis]) and kidney (eg, interstitial nephritis). These are akin to the inflammation occurring in the salivary and lacrimal glands (termed “autoimmune epithelitis” by some authors) and tend to be relatively stable and chronic.

Other extraglandular manifestations, such as glomerulonephritis and vasculitis, arise from immune-complex deposition. These develop most often in the context of cryoglobulinemia and may have a higher degree of morbidity and mortality compared with the immune response in ductal epithelial structures. Additionally, some manifestations relate to lymphoproliferation, such as lymphocytic interstitial pneumonitis (LIP) and lymphoma. The pathogenesis of other extraglandular manifestations is not well-understood; a prime example of this is the fatigue that occurs in many patients. The pathogenesis of SS is discussed in more detail separately. (See "Pathogenesis of Sjögren's syndrome".)

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Literature review current through: Oct 2017. | This topic last updated: Jan 07, 2016.
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