Tove R. Reksten, MPh, PhDa and Malin V. Jonsson, DMD, PhDab∗Malin.Jonsson@iko.uib.no,     aBroegelmann Research Laboratory, Department of Clinical Science, University of Bergen, The Laboratory Building, 5th Floor, Haukeland University Hospital, Bergen N-5021, Norway; bSection for Oral and Maxillofacial Radiology, Department of Clinical Dentistry, University of Bergen, Årstadveien 19, Bergen N-5009, Norway

∗Corresponding author.

Primary Sjögren’s syndrome (pSS) is an autoimmune chronic inflammatory disorder affecting 0.2% to 3.0% of the population, with a 9:1 female to male ratio. Features are oral and ocular dryness, local and systemic autoantibody production, and progressive focal mononuclear cell infiltration in the affected salivary and lacrimal glands. Lymphoma is the most severe complication of pSS, occurring in 4% to 5% of patients. Genetic studies identified an association with HLA and susceptibility genes in cytokine genes and genes involved in B-cell differentiation. Genetic variations may help explain why disease manifestations differ among patients and supports the hypothesis of certain distinct disease phenotypes.

Keywords

Primary Sjögren's syndrome

pSS

Autoimmune diseases

Inflammatory disorder

Epidemiology

Salivary glands

Pathogenesis

Key points

Introduction

Sjögren's syndrome is an autoimmune rheumatic disease characterized by focal mononuclear cell infiltration of the salivary and lachrymal glands.1 Primary Sjögren's syndrome (pSS) occurs alone, whereas secondary Sjögren's syndrome occurs in association with other autoimmune diseases, frequently rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).2 Signs of systemic autoimmune disease with musculoskeletal, pulmonary, gastric, hematological, dermatologic, renal, and neurologic manifestations may also be evident in patients with SS.1,3

Common complaints are dryness of the mouth (xerostomia), and difficulties with talking, tasting, and swallowing.4 Xerostomia is typically first noticed, as it becomes necessary to have chewing gum or lozenges on hand to stimulate saliva production, and by the urge to drink water during the night. Problems with speaking and eating due to reduced saliva secretion may ultimately lead to isolation of patients with the potential risk for depression and reduced quality of life, as well as severe problems linked to poor oral health.5 Changes in secretion and composition of saliva, and higher dental caries activity have been suggested as potential markers to determine the autoimmune salivary gland dysfunction in pSS.6

Dry eyes (keratoconjunctivitis sicca) are often described as a sensation of grit or sand in the eyes, redness, itching, and photosensitivity. As with saliva, the tear flow and tear composition is altered in patients with pSS.7 The dryness may also affect the airways, and reduced secretory capacity of sebaceous glands cause to be seen xerosis in up to 30% of patients with pSS.8 Other cutaneous manifestations include erythemas, vasculitis, and dermatitis.

Tiredness and fatigue are other disabling complaints in pSS, contributing to work disability and depression,9 and seem to remain mainly unchanged throughout the disease course.10 Extraglandular manifestations, such as arthralgia and myalgia are reported by up to 75% and 45% of patients, respectively,11,12 and Raynaud phenomenon is present in 10% to 15% of the patients, often preceding the onset of sicca symptoms.13

Prevalence and incidence

SS has been suggested to affect 0.2% to 3.0% of the population.14–16 It predominantly affects women between 40 and 60 years of age, with a 9:1 female:male ratio. Younger individuals and children may also be affected.1 Most epidemiologic studies are based on hospital registries and research cohorts and then extrapolated to the general population. Regional differences are not extensively known.

There is no specific test for pSS, and a range of classification criteria have been applied over the years. Differences in items concerning dryness symptoms and autoimmune features have resulted in variations in prevalence, and depending on which criteria are used to diagnose the patients, the reported prevalence of pSS varies in different populations and with gender. In a Norwegian population-based study of 2 age groups, the prevalence was determined to be 0.22% in those 40 to 44 years old and 1.4% in those 71 to 74 years old.17 In a local Norwegian population with 93% female patients, the prevalence was estimated at 0.05%.18 This is in line with 0.09%19 and 0.15%16 in Greece, less than 0.1% to 0.4% in Great Britain,15 and 0.17% in Brazil,20 whereas a Turkish study including only women reported a prevalence of 0.72%.21 A comparison of the recently introduced American College of Rheumatology (ACR) criteria for SS22 to the American-European Concensus Group (AECG) criteria2 showed 81% concordance in classification of pSS in 646 patients with sicca symptoms; 279 patients received the diagnosis by the AECG criteria and 268 by the ACR criteria. Regardless of classification, patients with pSS had similar gene expression profiles, which were different from healthy controls.23

The number of incidence studies of pSS is limited. A Slovenian study using the criteria from 199624 and an American study both suggested a yearly incidence of 3.9 per 100,000.25,26 Odds ratio for SS was, in an Italian study, found to be 7.4 if the individual had a first-degree relative with autoimmune disease, and for women the risk was slightly higher in women who had given birth, with an odds ratio of 2.1.27

Pathogenesis of SS