Sjögren's syndrome: Where do we stand, and where shall we go? (original) (raw)

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.

Current concepts on Sjögren's syndrome - classification criteria and biomarkers

European journal of oral sciences, 2018

Sjögren's syndrome is a lymphoproliferative disease with autoimmune features characterized by mononuclear cell infiltration of exocrine glands, notably the lacrimal and salivary glands. These lymphoid infiltrations lead to dryness of the eyes (keratoconjunctivitis sicca), dryness of the mouth (xerostomia), and, frequently, dryness of other surfaces connected to exocrine glands. Sjögren's syndrome is associated with the production of autoantibodies because B-cell activation is a consistent immunoregulatory abnormality. The spectrum of the disease extends from an organ-specific autoimmune disorder to a systemic process and is also associated with an increased risk of B-cell lymphoma. Current treatments are mainly symptomatic. As a result of the diverse presentation of the syndrome, a major challenge remains to improve diagnosis and therapy. For this purpose an international set of classification criteria for primary Sjögren's syndrome has recently been developed and valida...

Primary Sjögren’s Syndrome: Current Pathophysiological, Diagnostic and Therapeutic Advances

Autoimmune Disorders - Current Concepts and Advances from Bedside to Mechanistic Insights, 2011

The diagnosis of SS is currently essentially based on the American-European criteria. These criteria, 6 in total, include 2 subjective and 4 objective criteria. The subjective criteria are www.intechopen.com Autoimmune Disorders-Current Concepts and Advances from Bedside to Mechanistic Insights 42 ocular and oral symptoms, while the objective criteria are ocular signs, histopathology, salivary gland involvement, and autoantibodies. Experts have recommended making the diagnosis of SS when 4 of the 6 criteria are present, as long as histopathology or serology is positive, or when 3 of any of the 4 objective criteria are present (Vitali et al., 2002). It necessary to bear in mind that the most frequent symptoms of SS include the triad of fatigue, polyarthralgia and sicca symptoms, which are often commonly found in the general population and aging population. Many drugs have anti-cholinergic properties, which complicate the diagnostic process of SS. Exclusion criteria for the diagnosis of SS include the presence of hepatitis C and HIV viruses, sarcoidosis, prior cervical radiation, lymphoma, graft versus host disease and the use of anti-cholinergic drugs (Vitali et al., 2002). 2.1 Ocular symptoms Ocular symptoms are taken into consideration when patients complain about troublesome dry eyes, recurrent sensation of sand or gravel in the eye, or the use of tear substituent. 2.2 Oral symptoms Oral symptoms are considered pertinent when patients experience daily feeling of dry mouth, recurrent or persistent swollen salivary glands, or frequent drinking to facilitate dry food swallowing. 2.3 Ocular signs Evidence of ocular involvement relies on positive Schirmer's test (<5mm/min) or positive ocular dye score (score > 4 according to the van Bijsterveld score; Van Bijsterveld, 1969). 2.4 Histopathology A histological sign is considered positive when minor salivary gland biopsy show a focus score >1 (more than 50 lymphocytes per 4 mm 2 of tissue). 2.5 Salivary gland involvement Objective evidence of salivary gland involvement relies on low unstimulated saliva flow (< 1.5ml/15 min), abnormal sialography, or altered salivary scintigraphy. 2.6 Autoantibodies Serological signs are considered positive when the presence of antibodies to either Ro (SSA) or La (SSB) or both are detected in the serum. 2.7 New diagnostic tools To prevent excessive prescriptions of exams for establishing diagnosis of SS, newer diagnostic tools have been validated. However, these tools have not yet been included in the American-European diagnosis criteria of SS. For example, ultrasonography of salivary glands might prove to be useful to detect anatomical changes in parotid and submandibular glands, with similar diagnostic ability to sialography. Detection of hypoechoic areas, echogenic streaks, cysts and irregular gland margins are highly suggestive of SS (Tagaki et al., 2010). Parotid MRI can also prove to be an adjunct diagnostic tool to detect heterogeneity in salivary glands and specific cystic lesions (Roberts et al., 2008).

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.

Management of primary Sjögren’s syndrome: recent developments and new classification criteria

Therapeutic Advances in Musculoskeletal Disease

For many years primary Sjögren’s syndrome (pSS) has been considered an orphan disease, since no specific therapies were recognized as being capable of contrasting the development and progression of this disorder. The treatment of oral and ocular features, as well as of the systemic organ involvement, has been entrusted to the joint management of different subspecialty physicians, like ophthalmologists, otolaryngologists, dentists and rheumatologists. These latter subspecialty doctors are usually more involved in the treatment of systemic extraglandular involvement and, to do it, they have long been using the conventional therapies borrowed by the treatment schedules adopted in other systemic autoimmune diseases. The increasing knowledge of the biological pathways that are operative in patients with pSS, and the parallel development of molecular biology technology, have allowed the production and availability of a number of biological agents able to positively act on different diseas...

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...