Management of primary Sjögren’s syndrome: recent developments and new classification criteria (original) (raw)

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.

Topical and systemic medications for the treatment of primary Sjögren's syndrome

Nature Reviews Rheumatology, 2012

| The treatment of primary Sjögren's syndrome (SS) is based principally on the management of sicca features and systemic manifestations. Sicca manifestations are treated symptomatically through administration of topical therapies, such as saliva substitutes and artificial tears; in patients with residual salivary gland function, stimulation of salivary flow with a sialogogue is the therapy of choice. The management of extraglandular features must be tailored to the specific organ or organs involved; however, limited data have been obtained from controlled trials in SS to guide the treatment of systemic symptoms using therapies including antimalarials, glucocorticoids, immunosuppressive drugs and biologic agents. Nevertheless, randomised controlled trials of biologic agents that target molecules and receptors involved in the aetiopathogenesis of primary SS have initiated a new era in the therapeutic management of the disease, although the potential risks and benefits of these agents must be carefully considered. In this Review, we analyse the evidence regarding the efficacy of the therapeutic agents currently available to treat the manifestations of SS. On the basis of this evidence, we provide guidance on the use of these agents in different clinical scenarios.

Conventional Therapy of Sjogren’s Syndrome

Clinical Reviews in Allergy & Immunology, 2007

Sjogren's syndrome (SS) is a chronic autoimmune disorder affecting mainly middle-aged women. It is characterized by lymphocytic infiltration and destruction of the exocrine glands (mainly the salivary and lacrimal glands), resulting in dry mouth and eyes. Symptoms of SS are chronic and sometimes devastating, compromising the quality of life at a major extent. Despite its autoimmune nature, evidence for the use of immunosuppressive agents, which are the mainstay of therapy of diseases of autoimmune origin, is limited. Keratoconjunctivitis sicca (KCS), the main ocular manifestation of SS, is managed with tear substitutes, as well as local and systemic stimulators of tear secretion and supportive surgical procedures. Management of oral manifestations includes intense oral hygiene, prevention and treatment of oral infections, use of saliva substitutes, and local and systematic stimulation of salivary secretion. Cholinergic agents, such as pilocarpine and cevimeline are the cornerstone of current therapy in SS. Corticosteroids, cyclophoshamide, and nucleoside analogues are reserved for severe extraglandular manifestations of SS. The role of anti-B-cell therapy is a promising option for glandular and extraglandular manifestations of the disease, as well as for the management of SS-associated lymphoma.

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.

Sjögren's syndrome: Where do we stand, and where shall we go?

Journal of Autoimmunity, 2014

Primary Sjögren's syndrome (pSS) is one of the most frequent autoimmune systemic diseases, mainly characterized by ocular and oral dryness due to the progressive destruction of lachrymal and salivary glands by an inflammatory process. A noteworthy proportion of patients also features extraglandular manifestations, sometimes severe and life-threatening. Until now, its management relies mostly on symptomatic interventions, long-term monitoring, and, in patients with severe systemic complications, immunosuppressive drugs can be provided. However, recent years have seen great progresses in the understanding of the pathological processes of the disease. The central role of regulatory lymphocytes, the implication of the type 1 interferon pathway in some patients or the importance of epigenetics have been highlighted. New classification criteria have been recently published and have shed in light an international attempt for a better recognition of the patients, probably thanks to the development of new diagnostic procedures such as salivary gland ultrasonography. To facilitate the detection of treatment efficacy in clinical trials and to help in determining which subgroups of patients would have benefits from intensive therapies, a better definition of activity scores and the availability of new prognostic markers are urgent. Thereby, the development of future therapies should be based on specific molecular signatures that will enable a personalized management of each patient. This review focuses on the most striking advances in the fields of pathophysiology, diagnosis and treatment of pSS, which generate a great hope for pSS patients.

Biologic treatments in Sjögren's syndrome

La Presse Médicale, 2012

Pr imary Sjögren's syndrome (pSS) is a systemic immune-mediated condition in which inflammation of secretory (exocrine) glands typically leads to dry eyes and dry mouth and in some patients to chronic salivary gland swelling [1]. The secretory glands are infiltrated by focal aggregations of lymphocytes clustered around the salivary ducts and described as 'focal lymphocytic sialadenitis' on labial gland biopsy. Dryness of other surfaces such as the skin, vagina, bronchial tubes and gastrointestinal tract is common. Systemic features can also occur including variable, severe, debilitating fatigue, neuropathies, skin rashes (purpura, vasculitis),

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).

Ocular Involvement in Sjögren’s Syndrome: Advances in Therapy

Current Treatment Options in Rheumatology, 2018

Purpose This article seeks to identify immunomodulatory therapy that holds promise for managing the ocular features of Sjögren's syndrome. Recent findings There is an unmet need in therapies that can modulate the inflammatory damage that mediates keratoconjunctivitis sicca. While tear substitutes abound, there is a possibility that prevention of lacrimal gland and conjunctival inflammation may preserve tear production. Topical immunomodulatory therapy can improve some of the signs of keratoconjunctivitis sicca. Systemic immunomodulatory therapy appears to improve symptoms of ocular dryness, but improvement of signs of dry eye disease can be equivocal. Summary Topical immunomodulatory therapy can be effective in managing some of the signs of keratoconjunctivitis sicca. Systemic immunomodulatory therapy may play a role in managing or preventing the systemic inflammation that can lead to dry eye disease, but systemic therapy is currently employed when there are also systemic complications in Sjögren's syndrome. Future studies are needed to elucidate the utility of systemic immunomodulatory therapy in refractory cases of keratoconjunctivitis sicca.

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.