# Sjogren's Syndrome: The Role of Serological Profiles Versus Minor Salivary Gland Histopathology
## 1 Introduction  
Sjogren's syndrome (SS) is an autoimmune disease characterized by chronic inflammation that manifests with sicca syndrome--an array of dryness symptoms arising from impaired salivary gland and/or lacimal gland functioning [1, 2]. The chronic inflammation and autoantibody production lead to destruction of exocrine glands through mononuclear cell infiltration. On a microscopic level, chronic inflammatory cells are recognized in the salivary gland biopsy [3, 4] and/or the lacimal gland biopsy [4]. The etiology of SS remains unknown, though current discussion suggests an interaction between genetics, hormones, and environmental factors. Prior infection is also speculated to be a contributing part [2, 5]. There is no curative treatment for SS, and available treatment options are aimed principally at managing symptoms. Xerostomia (the subjective sensation of dry mouth) is a key complaint in oral manifestations of SS, and other symptoms--such as difficulty with eating, swallowing, speaking, and gustatory perception--are well discussed [6]. For the management of xerostomia and its associated symptoms, it is recommended that patients drink small amounts of water regularly, use chewing gum or lozenges to stimulate salivary secretion, use oral lubricants to substitute saliva, apply oral gels, and use specialized mouthwash and toothpaste, as well as oral rinses [7]. Xerophthalmia (dryness of the eyes due to inadequate tear production) is SS's most common ocular manifestation. Related ocular symptoms include a burning sensation, redness of the eyes, itching, and sensitivityto light [8]. Current therapeutic options for ocular manifestations of SS include artificial tear drops, immunosuppressant medications, and tear-stimulating drugs [7]. Other recommendations are humidity-preserving glasses and surgery to reduce fluid drainage from the eyes (punctal occlusion) [7; 9]. Overall, SS has strong implications for patient health outcomes, where studies show that having the disease exposes the patient to a higher risk for dental caries, oral and ocular infections [6; 8], lower quality of life [10], and an increased risk of lymphoma [2; 11]. Currently, there are no diagnostic criteria for SS. Instead, classification criteria are used to assist in the diagnostic work-up of patients [12], where the final diagnosis is made by considering the full clinical picture of each patient, involving a comprehensive evaluation of symptoms, clinical findings, and laboratory results. Newer studies also make the distinction of non-Sjogren's sicca syndrome patients (non-SS)--those who share the symptoms of dryness common to (primary Sjogren's syndrome (pSS) patients but do not fulfil the specific classification criteria [13]. This distinction is important as recent findings suggest that this group has a poorer general and oral health-related quality of life than SS patients, where individually tailored treatment would be desirable to achieve the best patient outcomes [13]. Commonly used criteria to classify patients with pSS include the 2002 American-European Consensus Group (AECG) classification criteria [14] and the 2016 American College of Rheumatology/European League Against Rheumatism (ACR-EULAR) classification criteria [15]. The complexity of the varying clinical presentations of SS suggests that a pSS diagnosis may be an umbrella term representing more than one pathology [16]. Yet, the possible number of pathologies and their pathogenesis remain unclear. Overall, there is a clear need to stratify SS patients in order to develop streamline treatment. There is a growing body of evidence that a positive focus score (FS)--defined as the accumulation of 50 or more inflammatory cells in a 4 mm\({}^{2}\) area of glandular tissue--correlates with disease severity, with research showing an association with the development of salivary gland dysfunction, extra-glandular manifestations such as arthritis, and the development of lymphoma [11; 17].