Abstract and Introduction
Abstract
SS is a chronic systemic autoimmune disease characterized by decreased exocrine gland function. A variety of other disease manifestations may also be present, including general constitutional symptoms and extraglandular features. A multidisciplinary approach focused on both local and systemic medical therapies is needed as the disease has a wide clinical spectrum. The current treatment for SS is mainly symptomatic. However, there is evidence that systemic drugs are effective in controlling extraglandular manifestations of the disease. Overall evidence for the role of conventional immunosuppressive therapy is limited. A number of attempts to use biologic therapies have led to variable results. Biologic agents targeting B cells, such as rituximab, epratuzumab and belimumab, have shown promising results, but further studies are needed to validate the findings. Early-phase studies with abatacept and alefacept proved that T cell stimulation inhibition is another potentially effective target for SS treatment. Modulation or inhibition of other targets such as IFN, IL-6 and Toll-like receptor are also currently being investigated. We have summarized the available evidence regarding the efficacy of biologic treatments and discuss other potential therapies targeting pathways or molecules recognized as being involved in the pathogenesis of SS.
Introduction
SS is a chronic, slowly progressive autoimmune disorder that affects the exocrine glands, presenting as persistent dryness of the mouth and eyes due to functional impairment of the salivary and lacrimal glands. It can occur in a primary form, not associated with other diseases, or in a secondary form that complicates other autoimmune rheumatic conditions. The most common disease associated with secondary SS is RA, but it can occur in association with SLE, progressive SSc or PM. The decrease in exocrine gland function leads to the sicca complex, a combination of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia). SS usually progresses slowly without major changes in symptoms. The exception to this benign course is the emergence of extraglandular features, such as skin, nervous system, pulmonary and renal involvement. The disease is also associated with a significantly increased risk of B cell lymphoma, which develops in ~5% of primary SS (pSS) patients. Typical serological findings in SS are the presence of ANAs, anti-Ro/SSA and La/SSB antibodies, RF and hypergammaglobulinaemia. The frequency of anti-Ro/SSA and/or anti-La/SSB antibodies is ~70–80% and 30–40%, respectively.
It is most commonly seen in Caucasian perimenopausal women, with a female preponderance of 9:1. It is postulated to be the second most common autoimmune rheumatic disorder, resulting in a substantial cost to the health service, estimated in the UK in 2004 to be £2188/patient (annual direct health cost).
Key to understanding the pathophysiology of SS is the observation that the main histological hallmark of this disease is mononuclear cell infiltration of the lacrimal and salivary glands with CD4 T lymphocyte predominance. Furthermore, this autoimmune disorder is associated with increased cytokine production (IFN-γ and IL-2), abnormal B cell activation and autoantibody production, leading to increased risk for B cell-derived malignancies. To improve our understanding of SS aetiopathogenesis, more studies are needed to elucidate the various pathways of abnormal cellular activation, establish the efficacy of available treatments and identify new potential therapies.