Sjögren’s syndrome, the old and the new

Abstract

Sjögren’s syndrome is a chronic autoimmune disease characterised by progressive injury to exocrine glands accompanied by diverse extra-glandular manifestations. The spectrum of Sjögren’s manifestations expanded in recent years to include new symptoms and signs such as small fibre neuropathy, and also well-defined activity and prognostic indexes. Similar to other non-organ-specific autoimmune diseases, a mosaic of factors have been linked with the development and appearances of Sjögren’s syndrome. Progress has been made unravelling those factors, including susceptibility genes, immunological parameters and various environmental factors in the last decade, some of which may enable targeted therapies, biological and non-biological ones, for patients suffering from this disease.

Thus, herein we review the postulated aetiologies, pathogenesis and new insights related to Sjögren’s syndrome.

Introduction

Sjögren’s syndrome (SS) is a chronic, autoimmune disease characterised by mononuclear cell infiltrate and progressive injury to the exocrine glands. SS typically manifests with dryness of the mouth and eyes, but may affect any exocrine gland as well as a wide variety of organs and systems. This syndrome may present as a primary disease (pSS) or in association with other autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis defining a secondary Sjögren’s syndrome (sSS) . SS is considered one of the common autoimmune diseases, affecting between 1% and 3% of the general population. Moreover, it has been estimated that up to 50% of pSS patients are currently undiagnosed, whereas up to 30% of patients with other autoimmune diseases can be diagnosed with sSS . Whilst all ages can be affected by this disease, it generally becomes overt during the fourth and fifth decades of life with a female-to-male ratio of 9:1 .

SS is triggered, like many other autoimmune conditions, by a mosaic of genetic, environmental and hormonal factors that ultimately induce immune dysregulation and loss of tolerance .

Although the precise mechanisms of SS development are yet to be elucidated, once overt SS is defined, B-lymphocyte hyper-reactivity, autoantibody production and T-cell lymphocytic infiltration to exocrine glands and other organs are usually observed .

In the current review we present old and new aspects of SS, relating to its clinical manifestations, ethio-pathogenesis and therapeutic approaches.

The clinical spectrum of SS

The hallmark of SS is decreased exocrine gland function termed the ‘Sicca syndrome’. The combination of dry eyes (xerophthalmia) and dry mouth (xerostomia) are the most common manifestations in both pSS and sSS. Xerostomia may result in excessive drinking, high incidence of dental complications, oral candidiasis, angular cheilitis, parotitis and bilateral enlargement of the parotid glands. Xerophthalmia is associated with corneal injury and recurrent eye infections that may lead to impairment of vision.

Involvement of other exocrine glands (i.e., respiratory tract, gastrointestinal and skin) is less common and may display as nasal crusts and bleeds, parotid or submandubular swelling, dry throat, cough, oesophageal mucosal atrophy, atrophic gastritis and dyspareunia. Extra glandular complains have been documented in up to 55% of patients ( Table 1 ), and the presentation of SS in younger ages (<35 years) correlates with more of these systemic manifestations .

Table 1

Frequency of systemic manifestations in primary Sjögren’s syndrome.

Clinical manifestations	Prevalence (%)	References
Arthralgia/arthritis	50–75
Skin involvement (xerosis)	Up to 55
Fatigue	Up to 50
Muscles pain	44
Fibromyalgia	22–27
Peripheral neurological symptoms	2–25
Pulmonary involvement	23–30
Thyroid dysfunction	10–45
Purpura/Vasculitis	11–30
Interstitial nephritis	5
Lymphoma	5