Sjögren's syndrome (SS) is a chronic, systemic, autoimmune disease that mainly affects the exocrine glands, especially the salivary and lacrimal glands, leading to the dryness of the mouth and the eyes, along with fatigue, joint and muscle pain with the prevalence between 0.05% and 1% in European population. Sjögren’s syndrome can be further subclassified as primary disease (primary Sjögren syndrome, pSS) or as a secondary disease (secondary Sjögren syndrome, sSS) when it is associated with another disease of connective tissue [1].
The pathogenesis of SS is complex. Genetic background and environmental factors including infections, stress and hormonal factors contribute to the pathogenesis of Sjögren’s syndrome with the important role of the immune cells of innate and adaptive immunity such as, dendritic cells (DCs), T and B cells. The hallmarks of SS are lymphocytic infiltration of the exocrine glands and the presence of circulating autoantibodies (anti-Ro/SS-A and anti-La/SS-B) [2]. Moreover, patients with pSS have autoantibodies directed against muscarinic acetylcholine type 3 receptors (M3R) which functionally inhibit salivary secretion [3]. Genetic susceptibility to pSS is evidenced by the presence of single nucleotide polymorphisms (SNPs) in human leukocyte antigen (HLA) alleles (HLA-DRA, HLA-DQB1, HLA-DQA1), STAT4, IRF5, IL-12A and TNIP1, genes involved in the function of innate and adaptive immune cells [4]. Moreover, several candidate genes that regulate matrix metalloproteinase 9 (MMP9) expression, the enzyme that degrades the salivary gland structures, have been identified in patients with pSS [5].
American-European consensus group (AECG) classification criteria are used for establishing the diagnosis of Sjögren syndrome [6]. These criteria include subjective presence of ocular dryness; subjective presence of oral dryness; objective measures of ocular dryness by Schirmer’s test or corneal staining; focus score > 2 in a salivary gland biopsy; salivary scintigraphy showing reduced salivary flow (1.5 mL in 15 minutes) and/or diffuse sialectasias and positive autoantibodies against SS-A and/or SS-B. Primary SS is diagnosed when 4 out of 6 items are present; either salivary gland pathology or the presence of autoantibodies against SS-A/SS-B is mandatory. If the patients have been diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or scleroderma prior to developing their sicca symptoms the diagnosis of secondary SS is made.
There is no cure for SS. The treatment of patients with SS is mainly symptomatic and the use of substitution therapy with artificial tears and saliva is recommended. Management of oral manifestations includes intense oral hygiene, prevention of oral infections and their treatment, use of artificial saliva, and local and systematic stimulation of salivary secretion [7]. Biological drugs could block several immune pathways or cytokines involved in the pathogenesis of SS, such as BAFF-APRIL pathway, T cell co-stimulation, IL-17 and IL-6 [8].
Dental erosions, dental caries, mucosal infection, ulcers and oral candidiasis are often present in patients with SS and are related to the decreased salivary flow and the qualitative changes in saliva. Due to the dryness of the oral cavity (xerostomia) the chewing, swallowing, speech and sleeping may be affected resulting in impaired quality of life in patients with pSS [9]. The impairments in olfactory and gustatory functions have been described in patients with pSS [10, 11]. Chemosensory disorders include gustatory and olfactory dysfunctions, which affect the senses of taste and/or smell and could lead to their reduced ability, distortion or absence [12, 13]. Many patients with chemosensory disorders experience burning sensations or numbness in the mouth, especially in or on the tongue. These sensations may originate in the gustatory nerve fibers [14]. Burning mouth syndrome (BMS) is defined as the burning sensation in the tongue (BST), or burning in other mucosal membranes, lasting for at least 4–6 months [15]. Patients with SS and burning mouth syndrome (BMS) often have similar oral complaints; however, these diseases have significantly different etiology, pathogeneses, diagnostic criteria, and treatment [16]. Halitosis (or oral mal-odor, defined as an unpleasant breath odor of oral or extra-oral origin) is another common oral complaint that can be associated with low salivary secretion or chemosensory disorders [17]. The presence of dysgeusia, BST and halitosis are associated with changes in oral health-related quality of life (OHRQoL) with no clear association with saliva secretion rates in patients with pSS [11]. Due to the fact that some reported data show no correlation between low salivary flow and taste performance it is still unclear whether hyposalivation causes smell and taste impairments along with burning sensation in the mouth [18]. Possible underlying cause of the olfactory and gustatory dysfunctions in patients with pSS could be related to immunopathological mechanisms operating in pSS. Systemic chronic inflammation in primary Sjögren’s syndrome is associated with overexpression of interferon–inducible genes [19] and proinflammatory pathways mediated by Toll-like receptors while interferons in taste tissue may interfere with normal taste transduction and turnover of taste bud cells [20].
Both, the patients and the physicians that take care of the patients with primary Sjogren`s syndrome (pSS), most frequently pay attention to the dry mouth and the dry eyes, along with the fatigue, joint and muscle pain as important signs and symptoms of the disease. However, some of the most important consequences of the nose and mouth dryness, the chemosensory dysfunction, as well as some of the important aspects of the oral disorders, dysgeusia, burning sensations in the tongue (BST), halitosis, and poorer oral health-related quality of life (OHRQoL) are often neglected. Moreover, some of the physicians and patients do not even realize that above mentioned chemosensory dysfunction and oral disorders are directly related to the pSS. The data regarding chemosensory dysfunction and other oral disorders, such as dysgeusia, burning sensations in the tongue and mouth in patients with pSS are limited. Therefore, it is of high importance to assess the impaired olfactory and gustatory functions, and occurrence of oral disorders in patients with pSS.
Patients with Sjögren’s syndrome commonly experience oral symptoms and they are often firstly examined by a dentist. Having in mind that prevention and early treatment are crucial for the maintenance of oral health in patients with pSS, dental professionals should recognize the signs and symptoms of xerostomia and immediately connect them to SS. Early and appropriate treatment of patients with pSS is important to prevent the development of chemosensory dysfunction and oral disorders. Oral hygiene and regular dentist care are of importance. In cases of dysgeusia and burning mouth disorder, tricyclic antidepressants and clonazepam can be helpful, but can also potentiate mouth dryness in patients with pSS [21]. In case of severe dysgeusia topical anaesthetics like lidocaine gel is indicated [22]. Artificial saliva may be helpful in patients with xerostomia [23]. Additionally, strategies that capitalize on non-olfactory components of food flavour (altering food texture, primary taste qualities, temperature, and colour) should be implemented to help maintain food enjoyment. Foods and beverages that are salty, sweet, or that stimulate the trigeminal nerve (e.g., black or red pepper, carbonation) may provide another dimension to the eating experience. Enhancing the olfactory component of food flavour can also improve food intake in patients with olfactory dysfunction. These compensatory strategies may help improve dietary choices and maintain both food enjoyment and nutritional health.
The aim of this study was to evaluate olfactory and gustatory function, dysgeusia, burning sensation in the tongue (BST), halitosis, and OHRQoL in patients with primary Sjögren's syndrome and to compare these findings with those of age- and gender-matched healthy controls.