Sjögren’s syndrome, the old and the new (original) (raw)

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

Journal of Clinical Medicine

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3–3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the salivary glands are now known to play an active role in the pathogenesis of the disease. The aetiology of the “autoimmune epithelitis” still remains unknown, but certainly involves genetic, environmental and hormonal factors. Later during the disease evolution, the subsequent chronic activation of B cells can lead to the development of systemic manifestations or non-Hodgkin’s lymphoma. The aim of th...

Treating Sjogren's syndrome: insights for the clinician

Therapeutic Advances in Musculoskeletal Disease, 2010

Sjögren's syndrome (SS) is a systemic autoimmune disease that affects the exocrine glands, mainly the salivary and lachrymal glands, with consequent persistent dryness of the mouth and eyes. In addition to the clinical manifestations related to the exocrine gland involvement, a consistent prevalence of patients may present systemic manifestations. Some of these can be ascribed to the periepithelial extension of lymphocytic infiltration whilst others are determined by an immunomediated process affecting small-or medium-size vessels. While the use of tear and saliva substitutes and local or systemic stimulation of residual secretions represent the mainstays of the therapy of sicca component, different immunomodulating or immunosuppressive agents are usually required to treat extraglandular features, similarly to what happens in other connective tissue diseases. In the last few years, the advancement in the understanding the pathogenetic mechanisms of this disorder and the availability of new biologic target therapies seem to offer completely new therapeutic options. The use of B cell depleting or modulating therapies has achieved promising results.

Sjögren’s syndrome: still not fully understood disease

Rheumatology International, 2014

hyper-reactivity and polyclonal production of immunoglobulins, and as a consequence, autoantibodies against pSS affected exocrine glands, especially lacrimal glands and salivary glands, but also other external glands such as the pancreas, mucous glands of the gastrointestinal and respiratory tract or bile secretion. In some patients, abnormal H+ secretion in the distal tubules has also been observed and caused distal renal tubular acidosis (type 1 RTA). In connection with the clinical symptoms which will result from the degree of attachment of these glands and epithelial injury, the pSS often uses the term "autoimmune epithelitis" or "autoimmune exocrinopathy" for better imaging of primary initiation sites of inflammation and autoimmunization. A brief history First lacrimal and salivary glands enlargement was described in a lecture of a Polish surgeon Jan Mikulicz-Radecki in 1888. In 1925, French dermatologists Henri Gougerot described a few cases of atrophy of the salivary glands with dryness of eyes, mouth and vagina. Later in 1933, Swedish ophthalmologists Henrik Sjögren in his doctoral thesis described keratoconjunctivitis sicca, and his description became a basis for pSS picture. Epidemiology It is estimated that primary Sjögren's syndrome occurs from 0.1 to 3.0 % in general population. The disease is more common for women (female/male ratio 9:1), mainly between the ages of 40-60, with the disease most frequently occurring around 50 years of age. Pathogenesis of pSS is not clear, nowadays several factors responsible for the development of the disease, such as Abstract Primary Sjögren's syndrome is an autoimmune disorder with external exocrine glands dysfunction and multiorgan involvement. The pathogenesis of primary Sjogren's syndrome is still unclear; however, our knowledge of the involvement of different cells (e.g., B and T cells, macrophages and dendritic cells) and pathways (BAFF/APRIL and interferons) leading to the development of autoimmunity is continually expanding. For clinicians, the most frequent symptoms are dryness of eyes and mouth, but often the patients have musculoskeletal symptoms and systemic manifestations. However, the increased risk of lymphoproliferative disorders in this group of patients, most commonly B-cell marginal zone lymphoma, is particularly important. Recent separation of IgG4-related diseases and attempts to create further diagnostic criteria for pSS testify to the difficulties, and at the same time a large interest, in understanding the disease so as to allow the effective treatment. This article draws attention to the problems faced by the clinician wishing to securely identify pSS by using accurate laboratory biomarkers and useful imaging tools and predict the development of complications associated with this, still not fully understood, autoimmune disease.

Sjögren’s syndrome: a systemic autoimmune disease

Clinical and Experimental Medicine, 2021

Sjögren's syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren's syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren's syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren's syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren's syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren's syndrome, starting from its pathogenesis to current therapeutic options.

Update on Pathogenesis of Sjögren's syndrome

Current rheumatology reviews, 2016

Sjögren's syndrome is a common autoimmune disease that presents with sicca symptoms and extraglandular features. Sjögren's syndrome is presumably as common as RA; yet it is poorly understood, underdiagnosed and undertreated. From the usual identity as an autoimmune exocrinopathy to its most recent designate as an autoimmune epithelitis - the journey of SS is complex. We herein review some of the most important milestones that have shed light on different aspects of pathogenesis of this enigmatic disease. This includes role of salivary gland epithelial cells, and their interaction with cells of innate and adaptive immune system. Non-immune factors acting in concert or in parallel with immune factors may also be important. The risk genes identified so far have only weak association, nevertheless advances in genetics have enhanced understanding of disease mechanisms .Role of epigenetic and environmental factors are also being explored. SS has also some unique features such as c...

Biological Therapy in Primary Sjögren's Syndrome: Effect on Salivary Gland Function and Inflammation

Frontiers in Medicine, 2021

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease. It is the second most common rheumatic autoimmune disorder, affecting 0.7% of European Americans and up to 1% of people globally. pSS is characterized by the impaired secretory function of exocrine glands, including salivary and lachrymal glands. A lymphocytic infiltration of these organs leads to the common and debilitating symptoms of oral and ocular dryness, majorly affecting the quality of life of these patients. Currently, no disease-modifying drug has been approved for the treatment of pSS, with therapies largely aimed at relieving symptoms of dry mouth and dry eyes. In particular, management of oral dryness still represents a major unmet clinical need in pSS and a significant burden for patients with this condition. Recently, several randomized clinical trials in pSS with biological therapies targeting specific mechanistic pathways implicated in the disease pathogenesis, including B-cell hyperacti...

Clinical and laboratory findings of primary Sjögren's syndrome patients without sicca symptoms

Clinical and Experimental Rheumatology, 2022

Objective Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by oral and eye dryness. A minority of patients can present without dryness but studies on their clinico-laboratory manifestations are scarce. Our purpose was to describe the clinical phenotype of pSS patients lacking sicca symptoms. Methods From a total of 1738 consecutive pSS patients fulfilling the 2016 ACR-EULAR criteria, those who presented without sicca symptoms were identified (non-dryness group). Their medical data was collected and compared with 2 control groups: a) the remaining unmatched sicca pSS patients with both oral and eye dryness (unmatched dryness group) and b) matched sicca pSS patients according to age, sex, and disease duration, in 1:2 ratio (matched dryness group). Results Thirty-eight (2.19%) patients lacked sicca manifestations presenting mainly with arthralgias (47%), parotid enlargement (24%), Raynaud's phenomenon (11%) and persistent lymphadenopathy (11%) that led them to be evaluated for pSS. Non-dryness pSS patients were younger than the unmatched sicca controls, displaying a higher frequency of anti-Ro/SSA antibodies (100% vs. 79.7%, p<0.001), ANA positivity (100% vs. 90.4%, p<0.001), neutropenia (20.8% vs. 7.5%, p=0.04) and thrombocytopenia (13.8% vs. 4.2%, p=0.04). They also had lower frequency of positive ocular tests compared to both unmatched and matched dryness patients. No differences were found between non-dryness pSS patients and both control groups regarding focus score or any other extraglandular manifestation. Conclusion pSS patients without sicca complaints constitute a distinct phenotype involving younger patients, sharing common immunopathologic mechanisms with typical sicca patients.