|Year : 2019 | Volume
| Issue : 1 | Page : 11-16
A comparative study of efficacy of intralesional corticosteroids and hyaluronidase therapy with and without ultrasound therapy in patients with oral submucous fibrosis
Harika Guduru1, Komali Garlapati1, Raji Viola Solomon2, Ancy V Ignatius1, Mounika Yeladandi1, Nithika Madireddy1
1 Department of Oral Medicine and Radiology, PMVIDS, Hyderabad, Telangana, India
2 Department of Conservative Dentistry and Endodontics, PMVIDS, Hyderabad, Telangana, India
|Date of Submission||17-Sep-2018|
|Date of Acceptance||18-Dec-2018|
|Date of Web Publication||23-Apr-2019|
Dr. Komali Garlapati
Department of Oral Medicine and Radiology, PMVIDS, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Oral submucous fibrosis (OSMF) is a potentially malignant disorder affecting any part of the oral cavity, sometimes pharynx associated with trismus and burning sensation. Physical therapies such as ultrasound therapy was found to have therapeutic benefits of decreasing inflammation and accelerating healing process in OSMF patients. Hence, this study was designed to evaluate the therapeutic benefit of ultrasound treatment when compared to empirical combination of intralesional dexamethasone and hyaluronidase treatment alone in OSMF patients. Objectives: To evaluate and compare the clinical efficacy of intralesional infiltration of 2 ml dexamethasone (4 mg/ml) + hyaluronidase 1500 IU, ultrasound therapy in combination with intralesional infiltration and only ultrasound therapy, in reducing the signs and symptoms in patients with OSMF. Materials and Methods: The present study was performed in the Department of Oral Medicine and Radiology, with a total sample of 33 participants grouped into Group A (intralesional infiltration of 2 ml dexamethasone 4 mg/ml + hyaluronidase 1500 IU dissolved in 0.5 ml of 2% lignocaine twice a week for 8 weeks), Group B (a combination treatment of intralesional infiltration twice a week for 8 weeks and ultrasound therapy for 15 days), and Group C (only ultrasound therapy for 15 days). The collected data were subjected to statistical analysis using SPSS 16 software. Results: Statistical analysis revealed that there was a significant difference in M.M.O in Group A (1.3 ± 0.48), Group B (2.55 ± 0.75), and Group C (1.65 ± 1.20) and also VAS score of 42% ± 0.10, 41% ± 0.13, and 15% ± 0.05, respectively, after treatment. Conclusion: The results revealed that therapeutic ultrasound can be used as an adjuvant treatment, as it can alleviate the signs and symptoms of patients suffering from OSMF, thus improving the quality of life.
Keywords: Intralesional injections, oral submucous fibrosis, ultrasound therapy
|How to cite this article:|
Guduru H, Garlapati K, Solomon RV, Ignatius AV, Yeladandi M, Madireddy N. A comparative study of efficacy of intralesional corticosteroids and hyaluronidase therapy with and without ultrasound therapy in patients with oral submucous fibrosis. J Indian Acad Oral Med Radiol 2019;31:11-6
|How to cite this URL:|
Guduru H, Garlapati K, Solomon RV, Ignatius AV, Yeladandi M, Madireddy N. A comparative study of efficacy of intralesional corticosteroids and hyaluronidase therapy with and without ultrasound therapy in patients with oral submucous fibrosis. J Indian Acad Oral Med Radiol [serial online] 2019 [cited 2019 Aug 21];31:11-6. Available from: http://www.jiaomr.in/text.asp?2019/31/1/11/256888
| Introduction|| |
Oral submucous fibrosis (OSMF) is a chronic disorder characterized by progressive fibrosis involving the oral cavity, oropharynx, and upper third of the esophagus, resulting in intolerance to spicy foods, a burning sensation in the mouth, xerostomia, and limitation of mouth opening, tongue mobility, swallowing, or phonation. The multifactorial etiology of OSMF include betel quid chewing, excessive use of chillies and spices, poor nutrition, and vitamin and iron deficiency. An increased risk of malignancy (7%–30%) is noted in OSMF.
Several studies were done to study the effect of various drugs and physical therapies in the management of OSMF. However, physical therapy such as ultrasound therapy, which was found to have therapeutic benefit in musculoskeletal disorders such as fibromyalgia, acute periarticular inflammatory conditions, and osteoarthritis, has been less explored in OSMF. Ultrasonic waves penetrate the skin to cause vibrations in tendons and soft tissues, providing gentle deep tissue heating that decreases pain and inflammation to speed healing in OSMF patients.
Hence, this study was designed to evaluate the efficacy of intralesional dexamethasone and hyaluronidase therapy with and without ultrasound therapy, as well as the role of ultrasound therapy alone in the management of OSMF patients.
| Materials and Methods|| |
Patients attending the Department of Oral medicine and Radiology in a private dental college between 2014 and 2016 were randomly screened, and those who are clinically diagnosed with Group II OSMF (Khanna JN and Andrade NN classification) were selected for study to evaluate and compare the efficacy of intralesional 2 ml dexamethasone (4 mg/ml) and hyaluronidase 1500 IU combination with and without ultrasound therapy and ultrasound therapy alone in patients with OSMF. This study was approved by the Institutional Ethical Committee (PMVIDS/OMR/0017/2014), and written consent was obtained from the patients before including them in the study.
Selection of sample
A prospective study of a total of 33 patients were randomly divided into three groups (Group A, B, and C), with 11 patients in each group. A detailed case history of patients with the details of their deleterious habits (chewing betel nut, pan parag, etc.) and a thorough clinical examination was recorded on a standard proforma. Patients with Group II OSMF based on Khanna and Andrade (1995) classification, with restricted mouth opening and interincisal distance of 26–35 mm and the clinical signs of associated blanched oral mucosa with palpable fibrous bands and burning sensation were included in the study.
- Patients with group II OSMF (Khanna and Andrade classification) were included in this study.
- Patients with OSMF who were not willing to participate in the study were excluded
- Group I, Group III, and Group IV (Khanna and Andrade classification) patients were excluded
- Patient with a known history of systemic diseases where steroids were contraindicated
- Pregnant women.
Burning sensation in the mouth was assessed using visual analog scale (VAS) with a score ranging from 0 to 10, where 0 means no symptom and 10 means most severe symptom perceived by the patient subjectively. The mouth opening (IID) between upper and lower incisal edges and tongue protrusion were recorded using a Vernier caliper and a metal scale. Incisional biopsy was done and histopathological examination was done to confirm diagnosis.
Ultrasound treatment device (Manual US mini, SAS 180, Delhi) with 3 MHz frequency, pulsed mode 1:1 (50% duty cycle), with an intensity of 2.5 W/cm2 was used [Figure 1]. The transducer of 5 cm diameter was applied over the cheeks bilaterally for 10 min for 15 consecutive days, with permissible one day off each week.
Group A: Patients were given intralesional infiltration of 2 ml dexamethasone (4 mg/ml) + hyaluronidase 1500 IU dissolved in 0.5 ml of 2% lignocaine twice a week for 8 weeks.
Group B: Patients were given a combination treatment of intralesional infiltration of 2 ml dexamethasone (4 mg/ml) + hyaluronidase 1500 IU dissolved in 0.5 ml of 2% lignocaine twice a week for 8 weeks and ultrasound therapy for 15 days.
Group C: Patients were given only ultrasound therapy for 15 days.
All 33 patients were also advised to perform physical exercises to increase the mouth opening with the help of ice-cream sticks and cheek blowing exercises for 10 min at least thrice daily. The clinical improvement in burning sensation, mouth opening, and tongue protrusion were recorded once in 3 days for a period of 15 days (2 weeks) in all groups, and later weekly recording in Group A and Group B until the completion of regime (i.e. remaining 6 weeks). The obtained data were compared.
The obtained data were subjected to statistical analysis using SPSS 16 software. A paired-sample t-test was used to analyze the improvement with the respective treatment modalities.
Analysis of variance test was used to compare the change in the mean mouth opening (MMO) and mean VAS scores among the three groups. Post-hoc Tukey test revealed the intergroup comparisons, explaining which treatment modality fared better. The P value of ≤ 0.05 was considered to be statistically significant.
| Results|| |
Out of total 33 patients, 82% (27) were males and 18% (6) were females [Table 1]. The mean age was 35.5 year, with a standard deviation (SD) of 11.5 years [Table 2].
|Table 2: Gender and age distribution among the participants in the study|
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The paired sample t-test in Group A patients revealed a significant difference in MMO before (27.80 mm) and after (29.10 mm) 15 days of treatment, with a mean difference (MD) of 1.3 mm and SD of ± 0.48 (P = 0.000*), further improvement in mouth opening after 8 weeks (35.70 mm) of treatment with MD of 7.90 mm and SD of ± 1.98 (P = 0.000*). The paired-sample t-test revealed a significant difference in burning sensation (VAS scores) before (73%) and after (31%) 15 days of treatment, with MD of 42% and SD of ± 0.10 (P = 0.000*), and further reduction in VAS score after 8 weeks (5%) of treatment with MD 68% and SD of ± 0.18 (P = 0.000*).
The paired-sample t-test done in Group B patients revealed a significant difference in MMO before (27.27 mm) and after (29.82 mm) 15 days of treatment with an MD of 2.55 mm and SD of ±0.7 (P = 0.000*) [Figure 2]. Further improvement in mouth opening after 8 weeks (35.86 mm) [Figure 3] of treatment with MD of 8.59 and SD of ± 1.59 (P = 0.000*) was also noted. The paired-sample t-test revealed a significant difference in burning sensation (VAS scores) before (60%) and after (19%) 15 days of treatment with MD of 41% and SD of ± 0.13 (P = 0.000*), and further reduction in VAS score after 8 weeks (0%) of treatment with MD of 60% and SD of ± 0.19 (P = 0.000*).
The paired-sample t-test done in Group C patients revealed a significant difference in MMO before (28.00 mm) and after (29.65 mm) 15 days of treatment with MD of 1.65 mm and SD of ± 1.20 (P = 0.003), and the paired-sample t-test revealed a significant difference in burning sensation (VAS scores) before (47%) and after (32%) treatment with MD of 15% and SD of ± 0.05 (P = 0.000*).
ANOVA analysis used to compare the change in MMO levels and VAS score among the three groups (Group A, Group B, Group C), revealed that there was a significant improvement with different treatment modalities (P < 0.05) [Graph 1] and [Graph 2].
ANOVA analysis revealed that there was an insignificant difference (P > 0.05) in the improvement in MMO levels among Group A and Group B, indicating that both groups fared similarly [Graph 3]. ANOVA was used to compare the change in the mean VAS scores among the two groups (Group A and Group B), and the analysis revealed that there was an insignificant difference in the change brought about by the two treatment modalities (P > 0.05), indicating that both groups fared similarly [Graph 4].
Post hoc Tukey test for intergroup comparisons revealed that there was statistically significant (P < 0.05) improvement in the mouth opening after 15 days (2 weeks) in Group B, and it was higher compared to Group A and Group C. There was statistically insignificant (P > 0.05) difference in improvement of the mouth opening between Group A and Group C patients. Post hoc Tukey tests show that improvement in mouth opening levels by Group A as compared to Group B treatment modalities showed that there was statistically insignificant difference among Group A and Group B patients (P > 0.05) [Table 3].
|Table 3: Comparison of mean difference in mouth opening between intralesional and combination treatment modalities at the end of 8 weeks by Post hoc Tukey test|
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Post hoc Tukey tests showed statistically insignificant difference in the reduction of VAS scores of Group A and Group B after 15 days indicating similar reduction in their VAS scores. However, there was statistically significant (P < 0.05) reduction in VAS scores in Group C compared to Group A and Group B after 15 days. Post hoc Tukey tests show that reduction in VAS scores by Group A compared to Group B showed no better reduction indicating similar reduction of VAS scores by Group A and Group B, and the difference was statistically insignificant (P > 0.05) [Table 4].
|Table 4: Comparison of mean difference in the burning sensation (VAS) between intralesional and combination treatment modalities at the end of 8 weeks by Post hoc Tukey test|
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All 33 patients (100%) had tongue protrusion ranging from 16 mm to 28 mm, with a mean 19 mm and SD of 5. Approximately 15% of the patients had blanching in the floor of the mouth without any restrictions of tongue movements.
| Discussion|| |
OSMF is a chronic disease of insidious onset with the deposition of fibrous tissue in the submucosal layer of the pharynx, palate, fauces, cheek, lips, and esophagus. Global estimates of OSMF show confinement among Indians and Southeast Asians, with the overall prevalence rate in India ranging from 0.2% to 0.5%. The etiology of OSMF is considered multifactorial. The habit of areca nut chewing is the common etiological factor of OSMF in the Indian subcontinent. In the present study, 78% of OSMF patients were in the age group of 20–40 years. Our results are in accordance with previous studies by Arakeri et al. with reported mean age of 28 years, 20–40 years by Galchar et al., and 21–40 years by Ranganathan et al. The prevalence of OSMF in this group can be related to changing lifestyles of individuals, peer influence, stress, addiction, etc., The present study shows a definite male predominance (82% male vs 18% female) among OSMF cases. It is in accordance with the previous studies conducted by Rupak et al. and Ganapathy et al. Higher males skew is predominantly due to easy product accessibility and changing lifestyles of the youngsters.
In the present study, all patients had the habit of chewing commercially available areca nut and tobacco products. Blanching of the buccal mucosa, soft palate, palpable fibrous bands, decreased cheek flexibility, reduction in the mouth opening, and burning sensation were the clinical symptoms observed in all OSMF group II patients (100% of the sample).
In the present study, restricted mouth opening was the clinical symptom in 33 (100%) of OSMF patients, with mouth opening ranging from 25 to 33 mm. This is consistent with a study done by Arora and Deshpande, in which trismus was the main presenting symptom in all 30 (100%) patients.
There are various treatment modalities in the management of OSMF, with ultrasound therapy being one among them. Recent success by physiotherapists in the treatment of OSMF subjects through ultrasound therapy, wherein energy deposits in tissue to induce various biological effects has been advocated in patients who are not compliant with conventional treatments. Early applications of ultrasound therapy was done using the mechanism of tissue heating (Lehmann, 1953).
The therapeutic ultrasound machine used in the present study (Manual US mini, SAS 180, Delhi) has two frequency setup, i.e. 3 MHz or 1 MHz. The intensity can be adjusted anywhere between 0.9 and 2.5 W/cm2 with either a continuous mode or pulsed mode. The therapy time can be adjusted in minutes on the device. In the present study, ultrasound therapy device (Manual US mini, SAS 180, Delhi) with 3 MHz frequency, pulse frequency 2.5 W/cm2, and duty cycle 50% for 10 min was used.
According to Draper et al., an increase of 1°C (mild heating) over baseline muscle temperature of 36.8°C to 37.8°C accelerates the metabolic rate in the tissue. Draper et al. found that 3-MHz ultrasound at 1.5 W/cm2 heated at a rate of 0.9°C/min, and therefore 3-MHz treatments are used for superficial tissues to a depth of approximately 1.6 cm.
A study was conducted by Vijayakumar and Priya using therapeutic ultrasound for 3–4 min on both the cheeks for 15 consecutive days with permissible one day off each week in OSMF subjects. Hence, in the present study, a similar procedure was followed.
In a study conducted by Galchar et al., in which 30 OSMF patients were divided in two groups. Group A received treatment in the form of ultrasound therapy and Group B received placebo ultrasound therapy and exercise for a period of 4 weeks; there was significant improvement in the symptoms of OSMF (mouth opening, VAS) in both the groups.
In the present study, dexamethasone (2 ml Decadron 4 mg/ml) injection and hyaluronidase 1500 IU with 2% lignocaine was administered, and there was significant improvement in mouth opening in Group A patients, which showed a significant reduction in the burning sensation VAS scores before and after 2 weeks of treatment.
In the present study, one out of the 11 patients showed no improvement in mouth opening even after 15 days, which might be due to the chronicity of the lesion and extent of fibrosis. In Group B patients, combination therapy with ultrasound therapy was planned to increase the effectiveness of intralesional (2 ml dexamethasone 4 mg/ml and hyaluronidase 1500 IU) treatment, enhancing their absorption into tissues and bring about synergistic effect.
In Group C patients, with ultrasound therapy, there was a significant improvement in the MMO and mean VAS scores levels before and after treatment, which were similar to the study done by Vijayakumar and Priya, in which there was significant improvement in MMO before and after 15 days of treatment with ultrasound therapy and evaluation after 3 months follow-up.
The reduction in VAS score for burning sensation in mouth was similar to the study conducted by Galchar et al., who hypothesized that the reason behind pain relief by ultrasound was directly influencing the transmission of painful impulses by eliciting changes within the nerve fibers and elevating pain threshold. On the other hand, indirect pain reduction occurs as a result of increased blood flow and increased capillary permeability to the affected area.
In the present study an extraoral therapeutic ultrasound device was used, and hence, we did not find any improvement in tongue protrusion.
Limitations of the present study are small sample size. A larger sample size could reduce the effect of confounding factors, and long-term ultrasound therapy would have been beneficial but patients compliance was questionable.
| Conclusion|| |
Ultrasound therapy for 15 days improved both mouth opening and burning sensation in OSMF patients, but ultrasound therapy alone was found to have less reduction of burning sensation when compared with combination treatment and only intralesional infiltration of 2 ml dexamethasone (4 mg/ml) and hyaluronidase (1500 IU) treatment. Ultrasound therapy showed synergistic effect in combination with intralesional infiltration of 2 ml dexamethasone (4 mg/ml) and hyaluronidase (1500 IU) by enhancing their absorption into the tissues.
Ultrasound therapy alone can be used as treatment modality in patients, especially in patients where there is absolute contraindication or intolerance to intralesional corticosteroids and in those with phobia for injections. Patient compliance was the main constraint in ultrasound therapy, and it is contemplated that if ultrasound therapy is given for longer period of time (≥ one month), the therapeutic benefits would be better and long lasting.
Hence, the present study suggested that ultrasound therapy can be given as an adjuvant treatment modality in OSMF patients.
Ethical committee approval
The study was approved by the Institutional Ethical Committee (PMVIDS/OMR/0017/2014)
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]