The Diagnosis and Treatment of Sjögren's Syndrome

Abstract

Background: Sjögren's syndrome is one of the more common inflammatory rheumatological diseases, with a prevalence of at least 0.4% in Germany.

Methods: This review is based on pertinent articles retrieved by a selective search in PubMed. Special attention is drawn to updated classification criteria and current treatment recommendations.

Results: Sjögren's syndrome has a wide variety of presentations, ranging from the local involvement of exocrine glands with keratoconjunctivitis sicca and xerostomia (the leading signs of the disease) to the systemic, extraglandular involvement of multiple organs. Fatigue also markedly worsens the patients' quality of life. Serologic testing reveals antinuclear auto-antibodies (anti-Ro/ SSA and anti-La/SSB) as well as rheumatoid factors. The histological hallmark of the disease is focal lymphocytic infiltration in otherwise normal-appearing glandular acini. The disease also markedly elevates the risk of non-Hodgkin lymphoma of the B-cell series, which arises in about 5% of patients. Primary Sjögren's syndrome (pSS) differs from the secondary form (sSS), which appears in the setting of another autoimmune disease, particularly systemic lupus erythematosus (15-36%), rheumatoid arthritis (20-32%), and limited or progressive systemic sclerosis (11-24%). Disease-modifying therapy is reserved for patients with systemic involvement; there is limited evidence for its efficacy. Because of the complexity of this disease, some of its clinical manifestations may require interdisciplinary treatment.

Conclusion: The main considerations in the interdisciplinary care of patients with Sjögren's disease are measures to improve quality of life, pharmacological and non-pharmacological treatments to keep disease activity in check, and management of the risk of lymphoma. Future therapeutic approaches must take the heterogeneity of the disease into account.

Figure

Diagnostic algorithm of Sjögren’s syndrome ANA, antinuclear antibodies; ENMG, electroneuromyography; ESSDAI, EULAR—Sjögren´s syndrome disease activity index; HRCT, high-resolution computed tomography; PFT, pulmonary function test

eFigure

Diagram of the pathogenesis of Sjögren’s syndrome (modified according to [e6]) Genetic predisposition (e2, e3), exogenous triggering factors (e.g. glandotropic viruses) and hormonal changes are thought to initiate and maintain the immunopathogenesis of the disease. Glandular epithelial cells supposedly play a central pathophysiological role in the development of auto-immune epithelitis, especially with regard to antigen presentation of Ro/SSA- and La/SSB-protein complexes which are found on the surface of apoptotic cells (19). Both the innate (e.g. pDC/monocytes) and the adaptive immune system (T-/B-cells) are involved in the initiation of the disease and perpetuation of the immune response (e5, e6). Via the activation of various CD4⁺ T-helper cell subsets, B cells play an important role in auto-antibody production, from the formation of ectopic germinal center-like structures to the malignant transformation to NHL (11). BAFF, B cell-activating factor of the tumor necrosis factor family; HLA, human leukocyte antigen; IFN ɑ/ɣ, interferon ɑ/ɣ; IL-1, -4, -12, -17, interleukin 1, 4, 12, 17; IRF5, interferon regulatory factor 5; LT-ɑ, lymphotoxin ɑ; LT-ß, lymphotoxin ß; NHL, Non-Hodgkin lymphoma; pDC, plasmacytoid dendritic cells; Tfh, follicular T cells; Th17, T helper cells 17; TNF-ɑ, tumor necrosis factor ɑ; Treg, regulatory T cells