Use of Topical Corticosteroids in Aphthous Stomatitis Systematic Review

Hussein, H., Zaky, A., Nadim, Yard., Elbarbary, A. (2021). Low-Level Diode Light amplification by stimulated emission of radiation Therapy (LLLT) versus Topical Corticosteroids in the Management of Recurrent Aphthous Stomatitis Patients. A Randomized Controlled Trial. Advanced Dental Journal, 3(4), 200-210. doi: 10.21608/adjc.2021.90071.1109

Heba Hussein; Ahmed Abbas Zaky; Menatalla Yard. Nadim; Ahmed Elbarbary. "Depression-Level Diode Laser Therapy (LLLT) versus Topical Corticosteroids in the Direction of Recurrent Aphthous Stomatitis Patients. A Randomized Controlled Trial". Advanced Dental Journal, 3, four, 2021, 200-210. doi: 10.21608/adjc.2021.90071.1109

Hussein, H., Zaky, A., Nadim, M., Elbarbary, A. (2021). 'Low-Level Diode Light amplification by stimulated emission of radiation Therapy (LLLT) versus Topical Corticosteroids in the Management of Recurrent Aphthous Stomatitis Patients. A Randomized Controlled Trial', Advanced Dental Periodical, three(iv), pp. 200-210. doi: 10.21608/adjc.2021.90071.1109

Hussein, H., Zaky, A., Nadim, M., Elbarbary, A. Depression-Level Diode Laser Therapy (LLLT) versus Topical Corticosteroids in the Management of Recurrent Aphthous Stomatitis Patients. A Randomized Controlled Trial. Advanced Dental Periodical, 2021; 3(4): 200-210. doi: 10.21608/adjc.2021.90071.1109

	Low-Level Diode Laser Therapy (LLLT) versus Topical Corticosteroids in the Direction of Recurrent Aphthous Stomatitis Patients. A Randomized Controlled Trial
Commodity 4, Book three, Effect four, October 2021, Page 200-210 PDF (324.19 K)
Document Blazon: Original Article
DOI: 10.21608/adjc.2021.90071.1109
Authors
1; Ahmed Abbas Zaky2; Menatalla Thou. Nadim3; Ahmed Elbarbary4
1Faculty of Dentistry, Cairo University
iiMedical Application of Laser Department, National Institute of Laser Enhanced Science (NILES) , Cairo University, Cairo, Egypt
3Department of Clinical Pathology, Faculty of Medicine, Ain Shams Academy, Cairo, Egypt
ivOral Medicine and Periodontology, Faculty of Dentistry, Cairo University
Abstract
Objectives: The current study was conducted to evaluate the outcome of depression-level laser therapy (LLLT) on recurrent aphthous stomatitis for reduction of pain score and ulcer size. Subjects and Methods: 28 participants with symptomatic small-scale recurrent aphthous ulcers were randomly allocated into two groups. The handling grouping received a 980 nm diode laser and the command grouping received topical triamcinolone acetonide 0.1%. The measured outcomes included pain score as visual analog scale (VAS) at baseline, 2d day, and seventh day, and the lesion size at baseline and 7th day. Results: A statistically meaning difference was constitute between the laser and the corticosteroid groups when comparing VAS scores on day two (pain reduction was -2.2 ± 0.9 and -4.786 ± one for corticosteroid and laser groups respectively with a p < /em>-value of 0.001) and mean solar day seven (pain reduction was -four.643 ± 1.646 and -half-dozen.071 ± 1.439 for corticosteroid and laser groups respectively with a p < /em>-value of 0.024) in favor of the laser grouping. Moreover, a statistically meaning divergence was noticed between the light amplification by stimulated emission of radiation and the corticosteroid groups regarding the subtract in lesion size (lesion diameter reduction was -3.036 ± one.447 and -4.536 ± i.846 for corticosteroid and laser groups respectively with a p < /em>-value of 0.024) in favor of the laser group. 2 participants experienced severe mouth dryness subsequently corticosteroid application. None of the laser patients experienced whatever side effects. Conclusion: LLLT can exist considered a reliable alternative to topical steroids in the management of recurrent aphthous ulcers since it was more effective in reducing both pain intensity and ulcer size.
Keywords
Recurrent aphthous stomatitis; Low-level light therapy; Recurrent aphthous ulcer; Diode light amplification by stimulated emission of radiation; Triamcinolone acetonide
Primary Subjects
Oral medicine
Full Text
Introduction: Recurrent aphthous stomatitis (RAS) is painful, idiopathic, recurrent, inflammatory ulcerations of the oral crenel. The lesion appears clinically every bit a round or oval-shaped ulcer with erythematous borders. RAS is classified into minor ( 1cm), and herpetiform (Edgar et al., 2017). As a painful experience, RAS can compromise the quality of life due to its interference with solar day-to-twenty-four hour period life activities (Zwiri, 2015). The mainstay of managing RAS is to decrease the hurting sensation and to accomplish a more swift healing process in addition to decreasing the number of episodes (Amorim dos Santos et al., 2020). Handling of RAS includes many medications such as corticosteroids, antiseptics, and anti-inflammatory agents. Multivitamins are also used based on the evidence of the deficiency of sure nutritional elements in RAS patients. Antibiotics and corticosteroids are provided in both topical and systemic forms. Systemic therapy is reserved for cases with more severe symptoms and more than frequent episodes. Nevertheless, some of these agents accept limitations due to their side effects or their minimal effect on decreasing recurrence (Huo et al., 2021). Topical corticosteroids are the most widely-used medications for managing RAS (Chiang et al., 2019). They exert a local anti-inflammatory outcome with minimal systemic absorption, and then they are used for treating many oral inflammatory weather including RAS (Hamishehkar et al., 2015). However, frequent or long-term apply of these medications in the oral cavity can result in undesirable side effects such every bit oral candidiasis (Ofluoglu et al., 2017). Recently, Low-level Laser Therapy (LLLT) has been proven to be constructive in treating a multitude of illnesses. This is due to its proven function in inflammatory modulation, improving tissue regeneration, the healing procedure, and hurting relief. These are results of activation of cellular proliferation, changes in levels of inflammatory mediators, and improving tissue oxygenation (Slebioda & Dorocka-Bobkowska, 2020). The low energy emitted from LLLT can guarantee prophylactic and foreclose whatever complications subsequently therapy (Ahmed et al., 2020). Other types of laser, like Diode, Nd: YAG, and not-contact non-ablative CO2 lasers have been used in the treatment of RAS (Tezel et al., 2009). This is considering the laser enhances both reepithelization and pain relief. Exposure to a low-powered light amplification by stimulated emission of radiation is believed to stimulate tissue reepithelization. It has been postulated that a low-power laser may improve tissue reepithelization past increasing respiratory metabolism which upregulates the mitotic activeness, epithelial proliferation, and collagen formation (Tezel et al., 2009). Information technology is suggested that the hurting relief caused by laser exposure is due to the electrical activity alteration in the neurons (Aggarwal et al., 2014). Some other suggested pain relief machinery by LLLT is enhanced ATP synthesis in the mitochondria due to the photo-receptors in the mitochondria absorbing the ruddy and infrared wavelengths which outcome in a hyperpolarization condition and the obstacle of activeness potential and hence the pain sensation (Wei Yu et al., 1997). A tertiary proposed mechanism involves prostaglandin E2 and interleukin-one (IL-one) beta inhibition (Shimizu et al., 1995). Diode lasers were found to stimulate aphthous ulcers pain relief and re-epithelization at a very low power setting (Jijin et al., 2016). In that location are very few trials evaluating the effect of LLLT on the direction of oral aphthous ulcers. So, the electric current study aimed to investigate the effect of LLLT on recurrent aphthous ulcers for hurting and lesion size reduction as compared to topical corticosteroids. Subjects and Methods: Study Design: This study was a randomized clinical trial. The Upstanding Committee of the Faculty of Dentistry, Cairo Academy approved the current study, under approval number xix 2 32, and all procedures were following the annunciation of Helsinki. Patients signed informed consent and were educated nearly the nature and objectives of the study. Participants: Patients were recruited from the Oral Medicine Clinic of the Faculty of Dentistry, Cairo University betwixt Feb 2019 until August 2021. Sequent patients diagnosed with minor aphthous ulcers were evaluated for report eligibility. Medical history was taken and a thorough medical test was performed on all the participants. Laser therapy was carried out at the Medical Application of the Light amplification by stimulated emission of radiation Section, National Institute of Laser Enhanced Science (NILES), Cairo University. The inclusion criteria of the patients involved diagnosis with symptomatic minor aphthous ulcer/s with a diameter smaller than one cm which appeared a maximum of two days before the day of examination. Exclusion criteria included patients with major aphthous ulcers, significant and lactating women, smokers, patients who were treated with any topical or systemic steroids during the previous month. The excluded patients were treated using topical corticosteroids just were not included in the study. Figure one demonstrates the written report's CONSORT flowchart Figure 1: The participants' flow chart Interventions: The subjects were randomly assigned to receive either LLLT or triamcinolone acetonide. Simple randomization was done using www.randomizer.org. Allocation darkening was done by placing the treatment assignment in sequentially numbered, opaque, sealed envelopes. Group A (intervention group) included 14 patients treated with a depression-level diode laser with a wavelength of 980 nm using a fiber optic diameter of 320 µm as shown in Effigy 2. The laser awarding was carried out using diode laser appliance (an Italian system (Quanta organization light amplification by stimulated emission of radiation). Before starting the handling, protective eyewear was used past the patient, the dentist, and the dental assistant. The treatment was washed in one sitting consisted of four sessions of low-level laser applications. Each session lasted 45 seconds with a gap of xxx-threescore seconds betwixt the sessions. The full laser application time was about 3 minutes. The light amplification by stimulated emission of radiation was applied in a non-contact mode with a 2-3 mm between the laser tip and the ulcer. The laser beam was practical in a continuous sweeping circular motility to encompass the entire ulcer surface especially when the ulcer is big. Those 30-60 seconds gap, sweeping motion of the laser beam, and the not-contact fashion were used to prevent overheating of the oral tissues (Aggarwal et al., 2014). Follow up session was performed after seven days. The patients were asked to keep a record of any post-procedural adverse effects over the following 7 days. Group B (control group): included xiv patients who were instructed to employ triamcinolone acetonide 0.one% (trade name: kenacort in orabase manufactured past GlaxoSmithKline pharmaceutical industry). All patients were instructed to employ the medication four times a day after meals and at bedtime for ane week. They were also told non to beverage or eat for at least 30 minutes afterwards handling application. Neither the patients nor the investigators could be blinded in this study due to its nature; however, the outcome assessor was blinded. Figure 2: Demonstrates the light amplification by stimulated emission of radiation device setting (left), and the application of the LLLT on the aphthous ulcer (right) Outcomes: The primary outcome of this report was pain score which was assessed using the visual analog scale (VAS) which is a scale from 0 to x, in which 0 means no pain and ten ways intolerable astringent pain, while the secondary outcome was lesion bore in mm measured using a periodontal probe. The pain score was assessed at baseline, ii days, and after one calendar week. The lesion bore was the secondary event assessed at baseline and one week. Sample size: The sample size was estimated based on (Aggarwal et al., 2014). The samples size for each group was xiv participants. Based on (0.02) α error, (95%) power and effect size of (0.four) with 2 arms and two consequence measures and expected missing information are around ten% per each grouping. Statistical analysis: Data were explored for normality using the Shapiro-Wilk test. Continuous variables were described equally mean and standard difference if they were normally distributed or median and range if they were not-unremarkably distributed. The inside-grouping comparison was performed using Wilcoxon signed-rank test for the diameter and Friedman exam for the pain score. The comparison between the two groups was performed using a two-tailed unpaired T-test (for normally distributed data) and a two-sided Mann-Whitney U test (for non-normal information). Conviction interval (CI) was calculated only for the commonly distributed data since not-parametric tests are rarely accompanied past CI. All statistical analyses were done using IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp. Differences were considered to be pregnant when the P-value was less than .05. Results: The study comprised 28 patients with the small-scale blazon of aphthous ulcer. The demographic data was described in table ane. There was no attrition during the trial. Ii participants experienced mouth dryness after corticosteroid application. No side effects were reported from the LLLT group. Table 1: Demographic data of the ii groups Corticosteroid group Laser group P- value Age (years) 28.v ±12.7 thirty ± 7.9 0.7 Gender (male person %) 36% 14% 0.001* *Variables are meaning when P-values less than .05 Both groups showed a statistically meaning decrease in ulcer bore compared to the baseline. Also, both groups showed a statistically significant decrease in pain between the unlike endpoints with a p-value Table 2: Intra-group comparison of the lesion bore using Wilcoxon signed-rank test Lesion bore (mm)** Corticosteroid group n=14 Light amplification by stimulated emission of radiation grouping northward=14 Baseline 3.5 (1,8) 6 (1, 9) Twenty-four hour period 7 0 (0,6) 0 (0, 4) p -value <0.001* <0.001* *Variables are significant when P-values less than .05 **Diameter was described as median and range at the timepoints Table 3: Intra-grouping comparison of the VAS differences using Friedman test VAS** Corticosteroid group n=xiv Laser group n=14 Baseline six.5 (1,eight) 6.5 (four,9) Mean solar day 2 iii.5 (0,v) 2 (0,iv) Day 7 1 (0,iii) 0 (0,2) p -value <0.001* <0.001* *Variables are significant when P-values less than .05 **VAS (ordinal data) was described as median and range at the timepoints A statistically significant decrease in lesion diameter was detected betwixt the laser grouping and the corticosteroid group with a p-value of 0.024 as stated in table 4. A statistically pregnant subtract in VAS on the 2d mean solar day was detected between the laser and the topical corticosteroid groups with a p-value of < 0.001. A statistically significant decrease in VAS on the 7th day was detected betwixt the laser and the topical corticosteroid groups with a p-value of 0.024 as stated in table v. Table 4: Inter-group comparison of the lesion diameter using unpaired T-test Lesion bore divergence (mm)** Corticosteroid group n=14 Laser group north=xiv Mean ± SD -iii.036 ±1.447 -four.536 ±i.846 p -value 0.024* 95% CI [-2.788, -0.212] *Variables are significant when P-values less than .05 ** Difference in diameter described as hateful and SD Table 5: Inter-group comparison of the VAS using Isle of mann-Whitney exam Lesion pain difference between baseline and solar day ii Lesion hurting difference between baseline and day 7 Corticosteroid group north=14 Light amplification by stimulated emission of radiation group north=14 Corticosteroid group n=fourteen Laser group n=xiv Mean ± SD -2.two ± 0.ix -4.786 ±one -4.643 ± i.646 -6.071 ± 1.439 Median (range) -1.5 (-1, -4) -4.5(-3, -6) -4.v (-1,-vii) -5.5 (-3, -9) p -value 0.001* 0.024* *Variables are pregnant when P-values less than .05 Discussion: Laser therapy has been widely used in the dental field due to its unique characteristics of being able to penetrate the tissues and biostimulate numerous benign biological processes. LTTT has anti-inflammatory and immunoregulatory capacities with confirmed action in pain reduction, bleeding control, and tissue healing stimulation (De Souza et al., 2010). Many studies demonstrated the use of laser in the management of RAU, but very few compared the result of LLLT with the topical steroid which is the widely used drug and is considered the first drug of selection in such cases (Agrawal et al., 2019). Hence, this was the rationale behind conducting this report. Recurrent aphthous ulcer are self- limiting unremarkably heals after 10-14 days (Edgar et al., 2017). Both interventions are hypothesized to shorten the duration of healing. So, seven days interval was chosen to evaluate the effect of both interventions before self-healing. And so, day seven timepoint was the most of import fourth dimension bespeak for the lesion diameter evaluation. Regarding hurting, many studies as Khaedmi et al., 2009;  Aggarwal et al., 2014;  Jijin et al., 2016 and Albrektson et al., 2017 concluded that laser is more significant in reducing the pain later 2-3 days, so day 2 time point was added for hurting score assessment. The results of the current written report showed that in that location was a statistically significant decrease in lesion diameter and hurting scores from baseline to the unlike report time intervals in each group separately. This is in accordance with the results of the report performed by Arabaci et al., 2009 who compared ND:YAG laser application versus the utilize of 0.1 % Triamcinolone in the direction of aphthous ulcers in patients suffering from Behcet syndrome. They recorded a statistically significant decrease in hurting scores and accelerated ulcer healing in both groups separately later 1, 4, and vii days. These results were also confirmed by Khaedmi et al., 2009;  Aggarwal et al., 2014;  Jijin et al., 2016 and Albrektson et al., 2017. They all demonstrated the clinical efficiency of LLLT in the reduction of hurting intensity with immediate relief on the same day or the few days next to LLLT application. The role of LLLT in decreasing pain was explained by its activeness in the increased release of endorphins and enkephalins (Lins et al., 2010). Another postulation is the induced ATP synthesis in mitochondria of neurons, allowing for hyperpolarization and hurting stimulus reduction, and fifty-fifty obstruction (Aga, 2007). Furthermore, LLLT was plant to cause a reversible change in the voltage-gated Na-K channels leading to inhibition in nerve fibers conduction (Yanagisawa, 2003). Similarly, the authors also confirmed in their studies the positive bear on of LLLT on the dispatch of recurrent aphthous ulcer healing. LLLT awarding in the direction of RAU led to a decrease in the inflammatory cytokines production every bit IL1, 6, and TNF α. In improver, a pregnant increase in growth factors and collagen type 1 gene expression, too as vascular endothelial growth factor (VEGF) production, was detected. Moreover, LLLT was constitute to induce fibroblast locomotion and promote fibroblast proliferation. (Basso et al., 2016) In the electric current study, the lesion bore decreased more in the light amplification by stimulated emission of radiation group than in the steroid grouping. There was a statistically significant difference between both groups regarding the change in lesion diameter after 7 days in favor of the laser grouping. Similarly, the decrease of hurting scores from baseline to twenty-four hours 2 and from baseline to day seven was college in the laser group than the steroid group with a statistically significant difference in VAS scores change in both groups in favor of the laser group whether at second or seventh day. This was confirmed past the randomized controlled trials conducted by Arabaci et al., 2009 and Tezel et al., 2009 who compared the change in pain scores betwixt light amplification by stimulated emission of radiation and topical steroid groups in patients suffering from RAU. They found a statistically significant difference in favor of the laser group with immediate and faster relief, while the pain gradually decreased in the steroid group by the fifth day. Regarding the healing, Tezel et al., 2009 did not evaluate the healing rate nor the lesion size in their study. In contrast to our study, Arabaci et al., 2009 when compared the healing betwixt both groups, a pregnant charge per unit of healing was detected in both groups with no statistically pregnant divergence between them. This might be justified by the use of the erythema and amount of exudate to evaluate the healing, unlike our study which used the change in the lesion'due south bodily size. In addition, they applied Nd:YAD light amplification by stimulated emission of radiation and the choice in our present study was diode laser. Moreover, Agrawal et al., 2019 in a prospective clinical study divided 77 patients into ii groups, group I was treated with laser, and grouping II was treated with triamcinolone acetonide 0.ane% in orabase. They reported that there was a meaning statistical divergence in pain score and functional disability between both groups in favor of the laser group whether on the same day or subsequently 3 days. On the reverse side,  the healing and reduction in ulcer size in their study showed no statistically significant divergence between both groups. The difference between their results and the results of our study apropos the reduction in ulcer size may be attributed to the fact that they monitored the ulcer but 3 days, unlike our study'southward follow upwards which was extended to 7 days. All of these findings ostend the superiority of LLLT over topical steroids in the management of RAU in terms of accelerated pain relief and faster ulcer healing. This goes along with the systematic review conducted by Khaleel et al., 2020 which included five randomized controlled trials comparing light amplification by stimulated emission of radiation therapy versus different topical medications which include triamcinolone acetonide among others. In all the included studies, the patients treated with LLLT reported lower hurting scores and shorter periods of aphthous ulcer healing. Conclusions and Limitations: From the present study results, we can conclude that the laser treatment of recurrent aphthous stomatitis tin be an easy, reliable, and effective treatment pick with no reported side effects. Yet, the operator must put into consideration the college cost of using LLLT when compared to topical steroids and should weigh the benefits in relation to the expenses. In improver, it is recommended to translate these results putting into consideration the limitations of the study such equally the failure of blinding both the investigator and the patients. Further studies with longer follow-up are needed to investigate the impact of LLLT on the recurrence rate of aphthous ulcers. Conflict of Involvement: The authors declare no disharmonize of involvement
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