|Year : 2020 | Volume
| Issue : 3 | Page : 235-240
Probiotics an adjuvant in the management of recurrent aphthous ulcer: A randomized clinical trial
Mercy S Yendluru, Rakesh K Manne, N Kannan, Aneesa Shaik Bepari, Adarsh Anumula, Sudeepthi Pulimi
Department of Oral Medicine and Radiology, Narayana Dental College, Nellore, Andhra Pradesh, India
|Date of Submission||20-Mar-2020|
|Date of Decision||26-May-2020|
|Date of Acceptance||27-Jun-2020|
|Date of Web Publication||29-Sep-2020|
Dr. Mercy S Yendluru
C.K.S.Theja Dental College, Renigunta Road, Tirupathi, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Recurrent Aphthous Stomatitis (RAS) is benign ulcerated lesions in the oral cavity. RAS is one of the most common ulcers and known to affect 20% of the population Aim: To assess the efficacy of probiotics as an adjuvant to tetracyclines in the management of RAS. The study was a randomized clinical trial. Materials and Methods: Forty participants were assigned to two groups. Group 1, 20 patients received Bacillus. coagulants (Sporolac) & Tetracycline capsules 250 mg (Resteclin) twice daily for 7 days. Group 2, 20 patients received only Tetracycline capsules 250 mg (Resteclin) twice daily for 7 days. Assessment of pain, size, and average duration of the ulcer was carried out at baseline, 4th and 7th day. Statistical Analysis: Comparison of the parameters between the two groups was performed using the Mann Whitney U test. Results: The Probiotic group achieved a significant reduction in all the parameters in 4 days. Conclusion: Probiotics acts as adjuvant therapy for the treatment and management of RAS.
Keywords: Aphthous ulcers, probiotics, tetracyclines
|How to cite this article:|
Yendluru MS, Manne RK, Kannan N, Bepari AS, Anumula A, Pulimi S. Probiotics an adjuvant in the management of recurrent aphthous ulcer: A randomized clinical trial. J Indian Acad Oral Med Radiol 2020;32:235-40
|How to cite this URL:|
Yendluru MS, Manne RK, Kannan N, Bepari AS, Anumula A, Pulimi S. Probiotics an adjuvant in the management of recurrent aphthous ulcer: A randomized clinical trial. J Indian Acad Oral Med Radiol [serial online] 2020 [cited 2020 Dec 3];32:235-40. Available from: https://www.jiaomr.in/text.asp?2020/32/3/235/296585
| Introduction|| |
RAS is considered as, the most common lesion of the oral mucosa also known as canker sores. The prevalence of RAS in India (2010–2012) is 21.7%. Ulcers are shallow and painful, usually characterized by a serous exudate in the ulcer floor and surrounded by a halo of inflammation. The disease is characterized clinically into 3 types: minor, major, and herpetiform. Minor RAU (MiRAU) is the most common, occurring in 75%–80% of patients. Minor RAS is frequently observed (80%) on nonkeratinized mucosa and characterized by painful, recurrent, small, round, clearly defined with circumscribed margins, erythematous halos, and yellow or gray pseudomembrane measuring 5mm in diameter (2–3mm in average) that typically heal between 7 and 14days without scarring. Major aphthae heal by scarring.
The etiology of the disease remains obscure and controversial, but probable factors, such as immunologic problems, environmental and psychological stresses, and viral infections have been suggested. Recurrence of RAS can be related to hereditary, psychosomatic, infectious, hormonal (periods, pregnancy or post-menopausal) factors, trauma, stress, food allergies, nutritional deficiencies (iron, vitamin B12, and folic acid), and hematological abnormalities. Recurrent oral mucosal lesions including RAS can cause a wide range of clinical signs and symptoms, some of which can have a considerable effect on the quality of life.
Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Probiotics can interact with and strengthen the immune system further preventing the diseases. Probiotics produce organic acids, bacteriocins, and peptide. Thereby they reduce the risk of colonization by pathogenic microorganisms. Tetracyclines reduce the pain by inhibiting prostaglandin production, suppress leukocyte activities, and inhibit collagenase and gelatinase activities as well as oxidative activation. This study was initiated to evaluate the efficacy of probiotics as an adjuvant therapeutic agent for managing RAS.
| Subjects and Methods|| |
The study is a randomized clinical trial conducted in recurrent aphthous ulcer patients who reported to Department of Oral Medicine and Radiology. The diagnosis of RAS was made based on its clinical appearance and the history given by the patients.RAS patients, presenting with 1 or multiple aphthous ulcers of less than 48 hours duration with a size <1cm or >1 cm in diameter are enrolled into the study. Nine (9) Major aphthous ulcers are included in this study. Fifty-five (55) patients were screened for the RAS, among them 15 patients were excluded because 8 patients didn't meet the inclusion criteria and 7 patients declined to participate in the study. Forty participants were enrolled and randomly allocated into two groups based on the parallel randomization method. Age and sex- matched controls were taken. Allocation sequences, and assigning interventions were implemented by the care provider and blinded to participants. All the patients received written and verbal information about the study and signed the informed consent form before the treatment.
(1) Patients willing to participate in the study (2) Episodes of aphthous ulcers (3) age criteria 18–50 yrs (4) Patients not taking any other medications.
(1) Oral mucosal ulcers other than RAS (2) Patients with systemic diseases like Behcet syndrome, Sweet syndrome, Periodic fever adenitis pharyngitis aphthous ulcer (PFAPA), Reiter syndrome, Crohn's disease, Gluten- sensitive enteropathy.(3) Pregnant or lactating women (4) Patients below 18 years.
Group 1, 20 participants (8 males and 12 females) received Bacillus. Coagulans (Sporlac) and tetracycline 250 mg (Resteclin) twice daily for 7 days. Sporlac should be taken 1 hour after antibiotic administration. Probiotic contents were mixed in 10 ml of water swished in the oral cavity for 1–3 min and swallowed. Tetracycline capsule contents were also mixed in 10 ml of water swished for 1–3 min and swallowed. Group 2, 20 participants (7 males and 13 females) received only tetracyclines capsules 250 mg (Resteclin) twice daily for 7 days. Capsule contents were mixed in 10 ml of water swished in the oral cavity for 1–3 min and swallowed.
Clinical examination was performed to assess the number, site, size with divider and scale, and pain using Visual Analog Scale (VAS) from 1 to 10, 0- absent, 1- mild, 5- moderate, and 10- severe. The difficulty in eating was recorded as yes/no. Patients who had more than 1 ulcer, the ulcer that occurred recently was chosen. Patients were recalled on 4th and 7th day for the assessment of ulcer healing, pain, and difficulty in eating. The effectiveness of the treatment in both groups was measured based on a reduction in all parameters. Periodic telephone conversations were made to supervise the administration of drugs.
The data were analyzed using IBM SPSS statistics (Statistical Package for Social Science) version 22 (Armonk, NY: IBM Corp). Descriptive data were presented in the form of frequency, the percentage for categorical variables and in the form of mean, median, standard deviation, and quartiles for continuous variables. Comparisons of the categorical variables between the study groups were performed using the Chi square test and fishers' test. A comparison of the parameters between the two groups at each time interval was performed using the Mann Whitney U test. P- value < 0.05 was considered as statistically significant.
| Results|| |
The study initially consisted of a total of 40 patients between 18 to 50 years of age. The mean age of occurrence of the aphthous ulcers in this study was found to be around 31.65 ± 14.08 yrs. 3 patients from Group 1 and 6 patients from Group 2 had to be excluded from the study on account of non compliance with the study protocol [Table 1]. The final study population consisted of a total of 17 patients in Group 1 and 14 patients in Group 2. Baseline values were recorded for each patient on the first day of reporting which included history of difficulty in eating food, number of the ulcers, size of the ulcers in both the groups [Figure 1] and [Figure 2] and the pain intensity recorded as VAS scores. The patients from the study group and the control group were recalled on the 4th and the 7th day for recording history of difficulty in eating food, number of the ulcers, size of the ulcers and the pain intensity recorded as VAS scores. These were statistically analyzed and compared with the baseline values.
Reduction in ulcer size in both groups showed no significant difference between 1st to 4th day [Table 2], [Figure 3] and [Figure 4]. Results were significant on the 7th day indicating a complete reduction of ulcer size in group 1 [Figure 5] compared with group 2[Figure 6]. At first visit, ulcer size of < 1cm in group 1 and 2 were 13 (76.5%) and 9 (64.3%) respectively. Patients having >1cm of ulcer size in group 1 and 2 were 4 (23.5%) and 5 (35.7%) respectively. On 4th day recall ulcer size was zero in 11 (64.7%) and 5 (35.7%) in group 1 and 2 and <1 cm in 6 (35.3%) and 9 (64.3%) resp. (p = 0.11). On the 7th day the ulcer size was zero in 17 patients of group 1 (100.0%) and 9 patients in group 2 (64.3%) and < 1cm in 5 patients (35.7%) in group 2. The ulcer size reduction on the 7th day was statistically significant (p = 0.01). The number of ulcers was also reduced significantly from day 1 to day 7 in group 1 compared with group 2. Statistically significant difference was observed at 7th day (p = 0.03)[Table 2].
|Table 2: Comparison of Ulcer Size at different time intervals between Group 1 and Group 2|
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Pain score in both the groups, at first visit mild pain was seen in 3 (9.7%) patients, moderate in 8 (25.8%) patients, and severe in 20 (64.5%) patients. At the second visit, the pain was zero in 18 (58.1%) patients, mild in 9 (29.0%) patients, moderate in 4 (12.9%) patients, respectively. At third visit the pain score was zero in 31 (100.0%) patients. The statistically significant difference in pain reduction was reported at the second visit (p = 0.009) [Table 3]. History of difficulty in eating was initially reported by 74.2% of the patients. A significant reduction of this discomfort was noted on the 4th day with only 32.3% of the patients giving a history of difficulty in eating and 100% relief was noted on the 7th day as none of the patients had any difficulty in eating. No statistically significant difference could be observed between both the groups [Graph 1].
|Table 3: Comparison of Ulcer Size, Number & Pain between Group 1 and Group 2 at different time intervals using Mann Whitney U Test|
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| Discussion|| |
The overall distribution, high frequency of RAS have resulted in a great deal of research into efficient therapy of this condition.RAS is an inflammatory painful phenomenon, characterized by necrotizing ulcers of the oral mucosa that persist, remit, and recur any time. Minor RAS mostly involves nonkeratinized mucosa. Major aphthae represent 10% to 15% of RAS cases, where the ulcerations are larger, of longer duration, and may leave a scar upon healing. Herpetiform aphthae represent 5% to 10% of all RAS cases, and present with multiple 1–3 mm painful ulcers, resembling herpes simplex outbreaks but involving nonkeratinized mucosa and with a duration of up to 14 days. WHO in 1994 described the probiotics as next most important in the immune defense system following antibiotic resistance.
Probiotics can create a biofilm, acting as a protective lining for oral mucosa against oral diseases. Use of probiotics in conjunction with antibiotics, can reduce the effects of the dysbiosis caused by the antibiotics, and maximize the benefits on the gut by immune stimulation. Probiotics will improve inflammation by exerting positive effects on the epithelial cells and mucosal immune system dysfunction that forms the basis of inflammation. Normal microbial flora is disturbed in conditions like an aphthous ulcer. Probiotics produce organic acids, bacteriocins, and peptide. Thereby they reduce the risk of colonization by pathogenic microorganisms. Restoration of eubiosis by probiotics can contribute to the remission of RAS. Probiotics compete with pathogenic agents for adhesion sites on the mucosa and also modify the surrounding environment by modulating the pH and/or the oxidation-reduction potential, which reduces the ability of pathogens to become established. Probiotics provide beneficial effects by stimulating nonspecific immunity and modulating the humoral and cellular immune response. In our study, both the groups had marked a reduction in the ulcer size, but Group 1 shows a significant reduction in the ulcer size on the 7th day compared with group 2 (p = 0.01). Probiotics combined with tetracyclines proved to be clinically beneficial in hastening the healing of the ulcers.
The degree of pain showed a marked reduction in both the groups within 3-4 days. There was a statistically significant difference between both the groups in pain reduction at the second visit (p = 0.004). The number of ulcers and difficulty in eating was reduced equally in both the groups on the 7th day. The pain improvement is related to the reduced production of Nitric Oxide (NO) powerful mediators of inflammation, which can modulate the production of inflammatory cytokines such as PGE2, IFNγ, MMPs, and TNFα. Our results are similar to Nirmala M et al., where Bacillus Clausii was administered to the patients, the mean number of ulcers and size of the ulcer reduced equally in both groups, whereas erythema and degree of pain significantly reduced in group A patients compared to group B (p = 0.001 and 0.0001, respectively) on day 5 of treatment. Moreover our results are in agreement with Nalini et al., there's a significant reduction in the size of the ulcer inpatients using probiotic lozenges. In their study, on day 10 follow up, patients in both groups had symptomatic improvement, with no significant difference in both groups.
Difficulty in eating due to ulcers was seen by 74.2% (23) patients at the first visit, 32.3% (10) patients at the second visit and complete relief by a total of 31 patients (100.0%) at third visit due to rapid healing of the ulcer. Improvement in quality of life regarding the difficulty in eating is similar to Albrektson M et al., which was moderate or severe for all participants during enrollment. In the laser group, 15 of 20 (75%) participants had moderate or severe difficulty on day 1, 4 of 20 (20%) on day 2, and none on day 3. Fast relief is obtained mainly due to higher wavelength and output.
| Conclusion|| |
This study demonstrated the efficacy and rapidity of response to probiotic as an adjuvant in the treatment of aphthous ulcer. The study has shown a reduction in number, size, and pain associated with ulcers with no side-effects attributed to probiotics and tetracyclines. Hence, probiotics along with tetracyclines is a useful adjuvant treatment modality for RAS. Infact studies on a larger sample for a longer duration are in need to see the recurrence of RAS.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The study was approved by the Institutional Ethical committee. (RC.no. NDC/PG/DISS/2015-16/EC/2015).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3]