Reviewing primary Sjögren's syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment

Abstract

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This process leads to sicca syndrome, which is the combination of dryness of the eyes, oral cavity, pharynx, larynx and/or vagina. Extraglandular manifestations may also be prevalent in patients with pSS, including cutaneous, musculoskeletal, pulmonary, renal, hematological and neurological involvement. The pathogenesis of pSS is currently not well understood, but increased activation of B cells followed by immune complex formation and autoantibody production are thought to play important roles. pSS is diagnosed using the American-European consensus group (AECG) classification criteria which include subjective symptoms and objective tests such as histopathology and serology. The treatment of pSS warrants an organ based approach, for which local treatment (teardrops, moistures) and systemic therapy (including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDS) and biologicals) can be considered. Biologicals used in the treatment of pSS mainly affect the total numbers of B cells (B cell depletion (Rituximab)) or target proteins required for B cell proliferation and/or activation (e.g. B cell activating factor (BAFF)) resulting in decreased B cell activity. The aim of this review is to provide physicians a general overview concerning the pathogenesis, diagnosis and management of pSS patients.

Keywords: B-cell.; T-cell; biologicals; epidemiology; extraglandular syndrome; pathogenesis; primary Sjögren syndrome; sicca.

Figure 1

Schematic showing a simplified overview of the pathogenesis of pSS with the targets for biologicals. An unknown cause (suggested to be a virus or immune complexes) may lead to activation of pDCs resulting in increased levels of interferons. Interferon-induced BAFF production leads to increased B cell proliferation and differentiation with autoantibody production as result. Abbreviations: pDC, plasmacytoid dendritic cell; Th1, T-helper 1 cell; IFN, interferon; B, B cell; PC, Plasma cell; Tfh, Follicular T-helper cell.