Sjögren''s syndrome: the diagnostic potential of early oral manifestations preceding hyposalivation/xerostomia

Sjögren's syndrome (SS) is a systemic autoimmune exocrinopathy that affects mainly the salivary and lacrimal glands, leading to progressive reduction in saliva and tear flow. Although the underlying immuno‐mediated glandular destruction is thought to develop slowly over several years, a long delay from the start of the symptoms to final diagnosis has been frequently reported. A limited knowledge concerning SS natural history is among the major causes of the actual diagnostic delay. Although very few studies have been focused on the analysis of SS early clinical onset, a series of oral features preceding xerostomia/hyposalivation development in patients eventually diagnosed as having SS have been reported. Sialochemistry alterations, salivary gland swelling, early dental loss and sialorrhea have been observed before the onset of typical signs and symptoms (namely xerostomia and/or hyposalivation), which usually lead to SS clinical presentation and diagnosis. Here we suggest, after evaluating available data, that the traditional ‘untouchable’ association between SS and xerostomia/hyposalivation might probably be reconsidered, and that astute clinicians should not underestimate the possible presence or development of SS in patients without xerostomia/hyposalivation and presenting these atypical early oral features.     

Qualitative mucin disorders in patients with primary Sjögren's syndrome: a literature review

Background It is a common opinion that Primary Sjögren Syndrome (pSS) damages the exocrine glands and determines the reduction of secreted saliva, some studies show that there are qualitative anomalies of the mucins produced in saliva, including MUC7, MUC5B, MUC1. The purpose of this study is to trace all the information useful to establish whether there is a qualitative or quantitative defect of the mucins in the pSS. Material and Methods We reviewed the literature by looking for publications relevant to the topic in electronic databases. Sixteen articles met the search criteria. The studies were divided into two categories, those that studied the rheological characteristics of the saliva and those that studied the structural and / or metabolism modifications of the muciparous cells in the salivary glands. Results in Patients with pSS, xerostomia and the reduction of salivary spinnbarkeit are only partially related to the reduction of the unstimulated salivary flow. In pSS, pathological alterations of mucins’ chemical-physical properties prevail as a cause of the clinical characteristics. Moreover, in pSS there are structural and metabolism changes in salivary glands’ muciparous cells. Conclusions There is much evidence that supports the presence of qualitative alterations in the saliva’s rheological properties in Patients with pSS, and these are the main cause, more than the reduction of the unstimulated salivary flow, of the disease clinical characteristics - dry mouth and complications in the oral cavity. Therefore we propose to add to the classification criteria of pSS also a qualitative test of salivary glycoproteins. Key words:Primary Sjögren''s syndrome, mucin, MUC7, MUC5B, MUC1, sulphate oligosaccharides.     

Oral and salivary parameters in patients with rheumatic diseases

We studied the presence of secondary Sjögren's syndrome (SS) and the composition of saliva, prevalence of oral pathogens, periodontitis, mouth mucosa, and teeth in patients with various rheumatic diseases and in healthy controls. The hypothesis was that different rheumatic diseases might cause differences in oral health characteristics because of the liability of secondary SS in the patients. The study involved 77 patients and 77 age-matched and sex-matched controls. Twenty patients were suffering from spondylarthropathy (SPA), 18 from ankylosing spondylitis (AS), 24 from rheumatoid arthritis (RA), and 15 from mixed connective tissue disease (MCTD). Clinical and radiographic oral health status was recorded and salivary flow rates were measured. Selected salivary proteins and immunoglobulins were analysed by routine methods. Minor salivary gland biopsy samples were taken from the patients for assessment of inflammatory focus scores. Differences between patients and controls and in between the different rheumatic diseases were analysed statistically. Secondary SS was diagnosed in 39% (30/77) of the patients. A severe periodontal condition (community periodontal index of treatment needs score 3 or 4) occurred in 58% (45/77) of the rheumatic patients compared with only 26% (20/77) of the controls (p<0.0001). The severity of focal sialadenitis (focus score) correlated significant with salivary IgA, IgG, and IgM concentrations. Salivary albumin, total protein, IgG, and IgM concentrations were higher in all patient groups than in the controls. The number of patients with low salivary flow rates was higher in all patient groups compared to controls. Oral yeast counts were significantly higher in the patients than in the controls (p<0.001). In a subgroup analysis, patients with SS had higher values for salivary IgA and IgM than patients without SS. Dental caries and oral lactobacilli were more frequent in patients with SS, but SS was not associated with periodontitis. No major differences were noted in other salivary biochemical parameters between these two groups. Patients with rheumatic diseases, irrespective of specific diagnosis, thus had various alterations in salivary flow and composition and oral health. The findings may reflect the autoimmune inflammation of the salivary glands frequently observed in these patients.     

The expression of the c-erbB-2 receptor protein in glandular salivary secretions

BACKGROUND: As the maintenance medium of the oral cavity, saliva is secreted from exocrine glands that include the parotid, submandibular, sublingual, and minor salivary glands. Considering that saliva is a fluid suffused with protein, it is possible that the solubilized by-products of oncogenic expression may be present in saliva. Recent studies suggest the presence of solubilized extracellular domain portion of the c-erbB-2 protein in serum, nipple aspirates, and saliva. As a consequence, the purpose of this study was to determine the presence and concentration of c-erbB-2 in major salivary gland secretions. METHODS: Fifteen healthy women had serum, stimulated whole (SWS), parotid (SP), and submandibular/sublingual (SS) salivary secretions collected. The specimens were analyzed for c-erbB-2 using enzyme linked immunosorbent assays (ELISAs). Western blots using c-erbB-2 were also performed on these specimens. RESULTS: The ELISAs revealed the presence of c-erbB-2 in SWS (24.50 Units/ml), SP (19.66 Units/ml), SS (15.59 Units/ml) and serum (1472.15 Units/ml). Western blots confirmed the presence of these 185 kDa proteins. CONCLUSIONS: These results suggest that the protein, c-erbB-2, is present in relatively equal amounts in both SP and SS glandular secretions. Elevated glandular salivary c-erbB-2 concentrations could be useful as a preliminary, non-invasive test in clinical decision making when diagnosing salivary gland carcinomas. Additionally, this marker may have utility in distinguishing between oral lesions that are benign, pre-malignant and malignant in the oral cavity. Further research is required to determine if these findings have clinical utility.     

Oral and salivary parameters in patients with rheumatic diseases

We studied the presence of secondary Sj?gren's syndrome (SS) and the composition of saliva, prevalence of oral pathogens, periodontitis, mouth mucosa, and teeth in patients with various rheumatic diseases and in healthy controls. The hypothesis was that different rheumatic diseases might cause differences in oral health characteristics because of the liability of secondary SS in the patients. The study involved 77 patients and 77 age-matched and sex-matched controls. Twenty patients were suffering from spondylarthropathy (SPA), 18 from ankylosing spondylitis (AS), 24 from rheumatoid arthritis (RA), and 15 from mixed connective tissue disease (MCTD). Clinical and radiographic oral health status was recorded and salivary flow rates were measured. Selected salivary proteins and immunoglobulins were analysed by routine methods. Minor salivary gland biopsy samples were taken from the patients for assessment of inflammatory focus scores. Differences between patients and controls and in between the different rheumatic diseases were analysed statistically. Secondary SS was diagnosed in 39% (30/77) of the patients. A severe periodontal condition (community periodontal index of treatment needs score 3 or 4) occurred in 58% (45/77) of the rheumatic patients compared with only 26% (20/77) of the controls (p < 0.0001). The severity of focal sialadenitis (focus score) correlated significant with salivary IgA, IgG, and IgM concentrations. Salivary albumin, total protein, IgG, and IgM concentrations were higher in all patient groups than in the controls. The number of patients with low salivary flow rates was higher in all patient groups compared to controls. Oral yeast counts were significantly higher in the patients than in the controls (p < 0.001). In a subgroup analysis, patients with SS had higher values for salivary IgA and IgM than patients without SS. Dental caries and oral lactobacilli were more frequent in patients with SS, but SS was not associated with periodontitis. No major differences were noted in other salivary biochemical parameters between these two groups. Patients with rheumatic diseases, irrespective of specific diagnosis, thus had various alterations in salivary flow and composition and oral health. The findings may reflect the autoimmune inflammation of the salivary glands frequently observed in these patients.     

Primary Sjögren''s syndrome (pSS): subjective symptoms and salivary findings

We studied the relationship between dry mouth, general health and objective findings in 16 patients having primary Sjogren's syndrome (pSS) according to the 1993 European classification criteria as well as in healthy controls. Serum autoantibody to SSA/SSB (AB) was correlated to unstimulated whole saliva flow (UWS) and labial salivary gland focus score (FS). All patients had dry mouth symptoms and UWS ≦ 0.10 ml/min, but patients with UWS < 0.05 ml/min and AB had more complaints of oral and ocular dryness. These patients also tended to have more exocrine and non-exocrine manifestations, and oral dryness had a greater impact on their self-reported general health than in patients with UWS ≧ 0.05 ml/min. Accordingly, we consider rating of oral dryness by visual analogue scales or categorised questionnaires to be valuable for the evaluation of oral involvement in pSS.     

The management of Sj?gren's syndrome in dental practice.

BACKGROUND: Sj?gren's syndrome, or SS, is a multisystem inflammatory disorder of the exocrine glands with a wide range of extraglandular involvement. Symptoms of dry eyes and xerostomia, although not invariably present, are characteristic features of SS. An increased risk of oral and dental diseases is a prominent consequence of SS. TYPES OF STUDIES REVIEWED: The author reviewed recent medical and dental studies that have advanced our understanding of the causes and treatment of SS. She particularly focused on studies addressing the diagnosis and treatment of the oral component of the disease. RESULTS: Sj?gren's syndrome is a widely underdiagnosed disease. A delay in the diagnosis of SS may have a significant physical, psychological and economic impact on the affected person. The pathogenesis of SS appears to involve a number of factors: immunological, genetic, hormonal and possibly infectious. Successful management of SS requires a multidisciplinary approach, and the dentist plays an essential role in the diagnosis and treatment of the disease. ORAL IMPLICATIONS: Impairment of salivary function in SS increases the risk of developing oral diseases. Effective management of oral health comprises enhancement of salivary output (cholinergic agonist drugs such as pilocarpine or cevimeline) and prevention and treatment of dental caries, oral candidiasis and allergic mucositis. Finally, periodic evaluation of various clinical and laboratory parameters is needed to monitor disease status.     

Sialochemistry in Sjögren''s syndrome: a review

Sjögren's syndrome (SS) is an autoimmune exocrinopathy. The salivary glands are the site of activated T- and B-lymphocytes, along with gradual parenchymal destruction, diminished flow and altered composition of the secretory product. At present, Sialochemistry has achieved no significance for the evaluation of SS patient. However, the number of sialochemical publications is steadily growing. This study review current sialochemical findings in patients with SS and relate the observations to the present concept of diagnosis, pathogenesis and prognosis of SS. An ideal combination of the collection of low-stimulated pure secretion, measurements of absolute flow-rates, and biopsy from the same glands seem to be unobtainable in SS patients. But two procedures may be appropriate: stimulated parotid secretion combined with parotid biopsies, or absorbance of low-stimulated labila saliva combined with labial gland biopsy. Sufficient data on disease-specific alterations in salivary composition in SS are still lacking. However, detection of specific changes in protein synthesis or in glycosylation as well as the detection of inflammatory cell products should be possible with the use of sensitive biochemical assays.     

舍格伦综合征的病情评价指数

舍格伦综合征（SS）,又称干燥综合征,是一种主要累及外分泌腺的慢性自身免疫性疾病。目前国际上主要的SS病情评价指数包括SS患者主观症状评价指数、累及全身系统表现的客观评价指数、疾病累积损害评价指数和患者生活质量评价指数。本文就SS的病情评价指数进行综述,简要介绍其发展背景、内容组成、评分规则,同时回顾目前在临床的应用现状,并对未来的发展前景进行展望。     

Comparison of salivary calmodulin binding proteins in Sjögren''s syndrome and healthy individuals

Background: Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS‐B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Methods: Saliva samples were collected from 20 patients and 20 age‐, race‐, and gender‐matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Results: Higher number of salivary CaMBPs was observed among patients than controls. Conclusions: The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease.     

Salivary gland disorders: A comprehensive review

Salivary glands are complex in nature. They could be either tubulo acinar, merocrine or exocrine glands secreting mainly saliva. Salivary gland is one of the main soft tissue structures in the maxillofacial area. Saliva is a clear, slightly acidic muco serous fluid that coats the teeth, mucosa and thereby helps to create and maintain a healthy environment in the oral cavity. Salivary glands may be affected by a number of diseases: local and systemic and the prevalence of salivary gland diseases depend on various etiological factors. The glands may be infected by viral, bacterial, rarely fungal or its ductal obstruction which may cause painful swelling or obstruction, affecting their functions. The salivary gland may also be affected by a various benign and malignant tumours. This review article briefly describes about the various salivary gland disorders, diagnostic techniques and their management including the recent advances and the future perspective.     

Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune disease affecting the exocrine glands, primarily the salivary and lacrimal glands. It has been suggested that exogenous agents may trigger SS in genetically predisposed individuals. However, at present, the etiology of SS is far from being understood, and no direct evidence for any of these triggers has been presented. The salivary and lacrimal glands from patients with SS harbor unique and highly selected T‐ and B‐cell populations. Disturbance in glandular cell apoptosis may be one possible explanation for the sicca symptoms in SS. However, discrepancies between glandular destruction and salivary flow give rise to processes causing glandular dysfunction preceding or triggering glandular cell destruction. Recent reports suggested autoantibodies inhibiting neuronal innervation of acinar cells and defective water transport to be implicated in salivary secretion deficiency observed in SS. Several types of autoantibodies have been suggested to contribute to the pathogenesis of SS. However, how the tolerance to these structures is broken down is unknown at present. Studies on B‐cell activating factor indicated that diminished apoptosis and disturbed B‐cell maturation could be responsible for the occurrence of autoreactive B‐cells and B‐cell hyperreactivity. B‐cell activation may also provide a basis for lymphoma development observed in up to 5% of the patients with SS.     

Salivary dysfunction and quality of life in Sjögren syndrome: a critical oral-systemic connection

BACKGROUND: The importance of oral health to systemic health and quality of life (QOL) is gaining attention. Although several studies have examined generic (general) QOL in Sj?gren syndrome (SS), little information exists on the effect of oral health on QOL and relationships among self-reported oral health, systemic health and objective clinical measures of health. The authors conducted this study to characterize these relationships in a sample of patients with SS. METHODS: Thirty-nine patients with a diagnosis of SS ascertained by means of the 2002 American-European Consensus criteria completed both the Oral Health Impact Profile (OHIP-14) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) QOL questionnaires. OHIP-14 measures pain; functional limitation; and psychological, emotional and social disability associated with the mouth. SF-36 measures physical and emotional health and the ability to perform usual activities. Additional measures included the number of self-reported autoimmune symptoms and an index of disease damage. Statistical analysis was performed by using hierarchical regression analysis. RESULTS: Both generic and oral health-related QOL were poor in these patients. Specifically, the findings indicated that salivary flow rate was correlated significantly with both Disease Damage Index and OHIP-14 ratings, the number of autoimmune symptoms was correlated significantly with both oral and generic QOL, and oral health accounted for a significant percentage of variance in SF-36 domains of general health and social function. CONCLUSIONS: Oral health appears to have an independent influence on general QOL in patients with SS. These findings underscore the importance of proactive dental management of the oral manifestations of SS. CLINICAL IMPLICATIONS: Dentists and physicians must work collaboratively to maintain oral health and quality of life for patients with Sj?gren syndrome. The dentist should address patients' concerns of xerostomia and hyposalivation in an aggressive manner.     

Loss of PKCδ results in characteristics of Sjögren's syndrome including salivary gland dysfunction

Oral Diseases (2011) 17 , 601–609 Objectives: Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren’s Syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C‐delta (PKCδ) is known to play a critical role in B‐cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B‐cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ?/? mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined. Materials and methods: Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages. Results: PKCδ?/? mice have reduced salivary gland function, B220+ B‐cell infiltration, anti‐nuclear antibody production, and elevated IFN‐γ in the salivary glands as compared to PKCδ+//+ littermates. Conclusions: PKCδ?/? mice have exocrine gland tissue damage indicative of a SS–like phenotype.     

The Salivary Gland and Systemic Health: Towards the Creation of Salivary Gland and Health Medicine

Salivary glands are intimately connected with the entire body via the nervous system and blood vessels, yet few studies have documented the effects of the salivary glands on the health of the whole body, although saliva has often been reported to possibly contain promising biomarkers of systemic disease states, including cancer. We therefore propose that the investigation of the effects of the salivary gland on the whole body and vice versa could introduce a new field of study, i.e., “salivary gland and health medicine.” This review examines data from novel studies on “salivary gland and health medicine” that were carried out by 3 different research groups.     

Oral health condition and saliva flow in southern Chinese with Sjögren's syndrome

Objective : To investigate the oral health condition and saliva flow of southern Chinese patients with Sjögren's syndrome (SS). Method : 51 SS patients (26 primary and 25 secondary cases) and 29 controls took part in this cross‐sectional study. Stimulated whole and parotid saliva flow rates, pH, and buffer capacity, and xerostomia, oral mucosal lesions, oral hygiene status, dental and periodontal conditions, prosthetic status were assessed and compared between groups. Results : Stimulated whole saliva (SWS) flow was reduced in primary and secondary SS cases (p<0.001), pH and buffer capacity were also reduced in the primary SS group (p<0.05). SS patients had a greater prevalence of xerostomia than controls (p<0.001). Primary SS patients had a higher mean DMFT, more missing teeth, and more prostheses than secondary SS cases and controls (p<0.05). SWS flow correlated negatively with the number of filled teeth in both SS groups (p<0.05) and the number of decayed teeth in the primary SS group (p<0.05). Conclusion : Despite good oral hygiene and regular dental checkups, the oral health of southern Chinese with primary SS was significantly compromised compared with secondary SS cases and controls, most probably due to the combined effect of impaired salivary gland function and poorer saliva buffer capacity.     

The rôle of saliva in maintaining oral health and as an aid to diagnosis

Saliva is a complex secretion. 93% by volume is secreted by the major salivary glands and the remaining 7% by the minor glands. 99% of saliva is water and the other 1% is composed of organic and inorganic molecules. While the quantity of saliva is important, so is its quality. The components of saliva, its functions in maintaining oral health and the main factors that cause alterations in salivary secretion will be reviewed, the importance of saliva in caries development and bacterial plaque formation will be discussed and its role as an aid to diagnosing certain pathologies will be examined. Variations in salivary flow can be affected, reversibly or irreversibly, by numerous physiological and pathological factors. Saliva plays an essential role in maintaining the integrity of the oral structures, in personal relationships, in the digestion and in controlling oral infection. The part that saliva plays in protecting teeth from caries can be summarised under four aspects: diluting and eliminating sugars and other substances, buffer capacity, balancing demineralisation/remineralisation and antimicrobial action. Saliva is a promising option for diagnosing certain disorders and monitoring the evolution of certain pathologies or the dosage of medicines or drugs. Its advantages as a diagnostic tool include its being easy to obtain and the positive correlation between many parameters in serum and saliva.     

Salivary gland disease in pediatric HIV patients: an update

Oral manifestations are one of the earliest clinical indicators of HIV infection and progression in children. Prompt recognition of these signs and symptoms by dental providers can help in the diagnosis and intervention of delaying the progression of HIV disease to AIDS. Salivary gland disease is a common manifestation of HIV infection in pediatric patients, presenting either as gland enlargement and/or xerostomia. The parotid glands by far are most frequently affected, though the other major glands are commonly involved. Diseases of the salivary glands and the corresponding quantitative changes in saliva affect the homeostasis of the oral cavity and account for significant morbidity during the progression of HIV disease. This paper summarizes the research on HIV-related salivary gland disease and outlines treatment and management considerations.