Year : 2013 | Volume
: 24 | Issue : 5 | Page : 567--570
Effect of sialagogue on bleeding on probing in Sjögren's syndrome
Medha Singh1, Athena Papas2,
1 Department of Oral Medicine, Infection and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Harvard University, Boston, MA, USA
2 Department of Oral Medicine and Public Health Research, Tufts University School of Dental Medicine, Boston, MA, USA
Department of Oral Medicine, Infection and Immunity, Division of Periodontology, Harvard School of Dental Medicine, Harvard University, Boston, MA
Background: Bleeding on probing (BOP) is a frequent observation in patients with Sjögren«SQ»s syndrome and a sialagogue is routinely prescribed for these patients.
Objective: The objective of this study was to evaluate the effect of sialagogue (muscarinic cholinergic agonists) on BOP in patients with Sjögren«SQ»s syndrome.
Materials and Methods: This observational study included 57 subjects. Study population was divided into two groups: Subjects on sialagogue (n = 32) and subjects not on sialagogue due to their side-effects (non-sialagogue, n = 25). The number of sites with BOP was recorded on all teeth.
Results: The subjects on sialagogue had a significantly lower mean (standard error) number of sites with BOP 22.97 (2.65) as compared with the non-sialagogue group 46.59 (6.20), P < 0.001. After adjusting for the use of remineralizing rinse the subjects on sialagogue had a significantly lower number of sites with BOP (P < 0.001).
Conclusion: In this observational study treatment with sialagogue may prevent BOP in patients with Sjögren«SQ»s syndrome.
|How to cite this article:|
Singh M, Papas A. Effect of sialagogue on bleeding on probing in Sjögren's syndrome
.Indian J Dent Res 2013;24:567-570
|How to cite this URL:|
Singh M, Papas A. Effect of sialagogue on bleeding on probing in Sjögren's syndrome
. Indian J Dent Res [serial online] 2013 [cited 2020 Oct 24 ];24:567-570
Available from: https://www.ijdr.in/text.asp?2013/24/5/567/123371
Sjögren's syndrome is the second most common rheumatic disease in the United States after rheumatoid arthritis. It is a chronic autoimmune disease. It affects approximately 1-4 million people. The majority of Sjögren's syndrome sufferers are Caucasian females and it has also been seen in men and children.  There are two types of Sjögren's syndrome, primary and secondary. Primary Sjögren's syndrome occurs independently of any other associated disorders or systemic disease. Secondary Sjögren's syndrome occurs in association with another connective tissue disease such as systemic lupus erythematosus, rheumatoid arthritis, scleroderma or relapsing polychondritis. Secondary Sjogren's syndrome accounts for approximately 60% of Sjögren's patients. 
The etiology of Sjögren's is unknown. Multiple factors are thought to be involved in its development such as the elevated levels of proinflammatory cytokines resulting in the inhibition of neurotransmission and the presence of Sjögren's associated autoantibodies (SSA/Ro and SSB/La).  To date there is no known cure for this disease. ,
The classic symptoms of Sjögren's include xerophthalmia (dry eyes) and xerostomia (dry mouth). Intraorally it affects the major salivary glands that are the parotid, submandibular and sublingual resulting in decreased salivary flow. ,
The major salivary glands are supplied with parasympathetic (cholinergic) nerve fibers. Parasympathetic stimulation evokes a copious flow of saliva. In contrast, sympathetic stimulation produces either a small flow, which is rich in protein or no flow at all. 
Sialagogue is non-selective muscarinic receptor agonists that are routinely prescribed for the treatment of dry mouth. These are parasympathomimetic drugs and act therapeutically at the muscarinic acetylcholine receptor and stimulated saliva (SS) production. The two most commonly prescribed sialagogue are pilocarpine and cevimeline.  Dry mouth when left untreated results in dental caries and periodontal disease. ,
The objective of the study was to evaluate the effect of sialagogue on bleeding on probing (BOP), a marker for gingival inflammation in patients with Sjögren's syndrome.
Materials and Methods
This prospective, observational study was the baseline data of a randomized clinical trial.  The Tufts New England Medical Center Institutional Review Board approved the protocol and informed consent of the study. A total of 57 subjects were enrolled in the study. All the subjects were females. The mean age of the study population was 61 years. All subjects had a confirmed diagnosis of Sjögren's syndrome as defined by the criteria by the American-European Consensus Group.  A total of 40 subjects were diagnosed with primary Sjögren's syndrome and 17 with secondary Sjögren's syndrome. The subjects received treatment for xerostomia (dry mouth) in the Oral Medicine Clinic at Tufts University School of Dental Medicine. The subjects were prescribed sialagogue (pilocarpine or cevimeline) for treatment of dry mouth. These subjects were seen routinely for dental exams and were getting periodontal prophylaxis to control dental plaque. The subjects were non-smokers and did not have any history of periodontitis.
The study population was divided into two groups: Subjects on sialagogue (n = 32) and subjects not on sialagogue (non-sialagogue, n = 25). All patients in the sialagogue group were on muscarinic agonists (pilocarpine or cevimeline) for at least 6 months prior to entry into the study. The subjects in the non-sialagogue group were not taking sialagogue as they were unable to tolerate the side effects of sialagogue (headaches, nausea and acid reflux). They had been off the sialagogue for at least 3 months. Of the 57 subjects, 28 were on prescription strength remineralizing rinse (Caphosol; ) for prevention of dental caries.
The inclusion criteria included the presence of a minimum of 10 teeth and a positive diagnosis of primary or secondary Sjögren's syndrome. The exclusion criteria included the history of advanced periodontitis, periodontal therapy (other than periodontal prophylaxis) in the past 12 months, history of antibiotic therapy in the past month or any condition that required antibiotic premedication or participation in any other clinical trial at time of being enrolled in this study.
The entire data (saliva collection and BOP) for the study was collected by the one examiner. Calibration for the collection of saliva samples (unstimulated saliva [US] and stimulated saliva [SS]) and BOP was done.
The saliva collection was standardized to keep accuracy in collection of samples and samples were measured on a calibrated scale.
US and SS function tests are used to determine the actual severity of xerostomia.  To collect US and SS the subjects were asked to fast for 90 min before the visit and to not brush or rinse before the morning saliva collection. US includes the output of the major and minor salivary glands. When performing this test, subjects were instructed to sit upright and allow saliva to accumulate passively in the mouth without swallowing. Unstimulated whole salivary flow rate US was collected by having subjects drool into a pre-weighed container for 5 min at 1-min intervals. An output of less than 0.1 mL/min is widely accepted as being abnormally low. 
SS was collected by following stimulation of the salivary glands. Stimulated whole salivary flow rate SS was collected by having subjects chew on paraffin wax and expectorate into a pre-weighed container every 30 seconds for 5 min. 
The number of sites with BOP was recorded on all teeth by a calibrated periodontal examiner using a periodontal probe (UNC-15, Dentsply International and York, PA). All six surfaces of the teeth were examined for BOP. The sites that bled were recorded.
The association between sialagogue and BOP was analyzed using an independent-samples t-test. After adjusting for the use of remineralizing rinse, the association between sialagogue and BOP was analyzed using two-way ANOVA. The association between SS flow, US flow and BOP was analyzed using linear regression.
The statistical software package used to analyze the data was statistical package for Social Sciences (SPSS) (SPSS Inc., version 16, Chicago, IL, USA).
In healthy individuals, the normal unstimulated whole saliva rate is 0.5 mL/min and values of less than 0.1 mL/min are considered abnormal. ,
This study population had salivary hypofunction as it had below normal levels of US and SS. The mean US for the entire population was 0.07 mL/min and mean SS was 0.84 mL/min; and the numbers of sites that were BOP was 34.
When comparing for BOP and sialagogue, the subjects on sialagogue had a significantly lower mean (standard error [SE]) number of sites with BOP 22.97 (2.65) as compared to the non-sialagogue group 46.59 (6.20), P < 0.001.
When comparing for BOP and remineralizing rinse, the subjects on remineralizing rinse did not have a significantly lower mean (SE) number of sites with BOP 34.84 (4.9) as compared to the subjects not on remineralizing rinse 33.42 (5.24), P = 0.84.
After adjusting for the use of remineralizing rinse, the subjects on sialagogue had a significantly lower number of sites with BOP, P < 0.001.
When analyzing between SS flow and sialagogue, the subjects on sialagogue did not have a significantly higher SS mean (SE) 0.84 (0.12) as compared to the non-sialagogue group 0.80 (0.13), P = 0.83.
When analyzing between US flow and sialagogue, the subjects on sialagogue did not have a significantly higher US mean (SE) 0.08 (0.01) as compared to the non-sialagogue group 0.05 (0.01), P = 0.34.
It is important to note that the SS was negatively associated with the number of sites with BOP and this association was statistically significant when not adjusting for unstimulated saliva (P = 0.01) and when adjusting for unstimulated saliva (P = 0.03). That is higher SS flow resulted in less the number of sites with BOP whereas the unstimulated saliva did not have effect on BOP. The US was negatively associated with the number of sites with BOP and this association was not statistically significant (P = 0.2).
Sialagogue is frequently prescribed for the treatment of xerostomia in patients with Sjögren's syndrome.  Sjögren's syndrome is a rheumatological disorder, in which there are high levels of inflammatory mediators that cause destruction. , Bleeding gums is a sign of gingival inflammation. , However, no previous research has been performed to examine the effect of sialagogue on BOP in patients with Sjögren's syndrome. In this study, we evaluated the effect of sialagogues on BOP in patients with Sjögren's syndrome.
BOP is a clinical evidence of gingival inflammation and if left untreated can result in periodontal disease. , Xerostomia causes an increased accumulation of bacterial plaque resulting in gingival inflammation and periodontal disease. Saliva contains lysozyme, lactoferrin, lactoperoxidase and secretory immunoglobulin which have antimicrobial properties. Presence of these antibacterial agents in the saliva may also help to reduce gingival inflammation. , Furthermore, saliva lubricates and protects the teeth and gingiva as it has a neutral pH.  This study suggests that sialagogue may prevent BOP in patients with Sjögren's syndrome by stimulating the salivary glands to produce saliva thereby decreasing the accumulation of bacterial plaque around the gingival margins of teeth, but further research needs to be done with a larger sample size.
The salivary flow rates of the two groups did not differ significantly as patients in the sialagogue group were on muscarinic agonists (pilocarpine or cevimeline) for at least 6 months prior to entry into the study. The subjects in the non-sialagogue group had been off the sialagogue for at least 3 months. This was a very short time period to see a significant difference between the two groups. Secondly, subjects diagnosed with primary Sjögren's syndrome had severe fibrosis of the salivary glands. Even though subjects were taking sialagogues, the medications cannot restore adequate salivary flow due to the severe salivary gland fibrosis and scarring. Early diagnosis is essential in Sjögren's syndrome to prevent fibrosis and destruction of the salivary gland and enable adequate salivary flow with the usage of sialagogues. Lastly, in this observational study the results were not significant, when comparing effect of sialagogue on stimulated whole salivary flow due to a small sample size. Further research needs to be done, utilizing a larger cohort of patients with Sjögren's syndrome.
Sialagogues should always be taken with food. When taken on an empty stomach they cause headaches, nausea and acid reflux.  Dry mouth patients are at high risk for periodontal disease. Importance of regular brushing and flossing should be reinforced and use of an electric toothbrush should be recommended to effectively remove plaque and prevent gingivitis.  It is recommended that patients having a diagnosis of dry mouth receive periodontal prophylaxis every 3 months to arrest periodontal disease and periodontal prophylaxis be followed by an in-office application of fluoride varnish. An antibacterial rinse such as 0.12% chlorhexidine gluconate (e.g. Actavis Mid Atlantic LLC) is indicated in an effort to reduce gingivitis. ,
Treatment with sialagogue may help in the prevention of BOP in patients with Sjögren's syndrome. No previous research has been performed to examine the effect of sialagogue on BOP in patients with Sjögren's syndrome. In this observational study, the results were not significant when comparing effect of sialagogue on stimulated whole salivary flow due to a small sample size. Further research needs to be done, utilizing a larger cohort of patients with Sjögren's syndrome. Preventive care and mouth rinses did not have any effect on BOP.
Dr. Medha Singh was the co-investigator responsible for the implementation of the research project and data collection in the study. Dr. Singh is the primary author of the manuscript.
Dr. Athena Papas was the principal investigator responsible for the design and implementation of the study.
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