|Year : 2015 | Volume
| Issue : 3 | Page : 387-392
Efficacy of vitamin E in oral submucous fibrosis: A clinical and histopathologic study
Venkateswarlu Nallapu1, Bhavya Balasankulu1, Hima Bindu Vuppalapati1, Sailaja Sambhana1, Dayanandam Mala1, Sri Krishna Koppula2
1 Department of Oral Medicine and Radiology, Government Dental College and Hospital, Hyderabad, Telangana, India
2 Department of Oral Medicine and Radiology, Hazaribag College of Dental Sciences, Hazaribag, Jharkhand, India
|Date of Submission||10-Jan-2015|
|Date of Acceptance||07-Nov-2015|
|Date of Web Publication||25-Nov-2015|
Department of Oral Medicine and Radiology, Government Dental College and Hospital, Afzalgunj, Hyderabad - 500 012, Telangana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Oral submucous fibrosis is a scarring progressive disease characterized by juxta-epithelial inflammatory reaction and progressive fibrosis of the submucosal tissues, i.e., lamina propria and deeper connective tissues. An attempt was made in this study to evaluate the role of vitamin E in the treatment of oral submucous fibrosis by carrying out a comparative study between regular intralesional dexamethasone, hyaluronidase, and local anesthesia with and without oral vitamin E capsules. Materials and Methods: Twenty histopathologically confirmed oral submucous fibrosis cases were randomly selected and divided into two groups, with 10 cases in each group. Group A patients were given intralesional dexamethasone 2 ml (2 mg/ml), hyaluronidase (1500 IU), and 0.2 cc lignocaine (2%), every week. In addition, group B patients were given oral vit E capsules, 400 IU OD, for a period of 8 weeks. Weekly follow-ups were done. Results: Addition of vitamin E to the conventional treatment had synergistic effect with more improvement in the patient's condition in terms of burning sensation, vesiculation/ulceration, pigmentation, paleness of oral mucosa, tongue protrusion, and extent of mouth opening, which was confirmed histopathologically. Conclusion: Vitamin E has a significant role in the improvement of oral submucous fibrosis, which was proven in the present study.
Keywords: Dexamethasone, hyaluronidase, oral submucous fibrosis, vitamin E
|How to cite this article:|
Nallapu V, Balasankulu B, Vuppalapati HB, Sambhana S, Mala D, Koppula SK. Efficacy of vitamin E in oral submucous fibrosis: A clinical and histopathologic study. J Indian Acad Oral Med Radiol 2015;27:387-92
|How to cite this URL:|
Nallapu V, Balasankulu B, Vuppalapati HB, Sambhana S, Mala D, Koppula SK. Efficacy of vitamin E in oral submucous fibrosis: A clinical and histopathologic study. J Indian Acad Oral Med Radiol [serial online] 2015 [cited 2022 Aug 7];27:387-92. Available from: https://www.jiaomr.in/text.asp?2015/27/3/387/170467
| Introduction|| |
Oral submucous fibrosis (OSMF) is a chronic mucosal disease considered a potentially malignant disorder (PMD).  It was first described by Schwartz in 1952.  Etiology of OSMF is obscure. Habits like betel nut, tobacco chewing and eating spicy foods are thought to be the predisposing factors. There are various treatment modalities for this entity. One of the widely accepted treatments is intralesional dexamethasone infusion with fibrinolytic agents like hyaluronidase along with vitamin therapy. The present study was conducted to study the efficacy of vitamin E which was administered orally along with the accepted therapy of intralesional injections in OSMF. The effect of vitamin E was also studied histopathologically to substantiate the clinical assessment.
| Materials and Methods|| |
Twenty histopathologically confirmed OSMF patients were divided into two groups of 10 each irrespective of age, sex, clinical presentation, or degree of involvement.
- Subjects of all age groups, including both males and females of all socioeconomic statuses.
- Histopathologically confirmed OSMF cases with the following clinical features: Burning sensation on intake of hot and spicy foods and beverages, vesicle formation and ulceration, pigmented and pale mucosa, limitation in tongue protrusion, gradual reduction in mouth opening, and palpable fibrous bands.
- Patient's consent for participation in the study (including consent for taking medication and for biopsy).
In the present study, group A patients received intralesional injections bilaterally on the buccal mucosa [dexamethasone 2 ml (2 mg/ml), hyaluronidase (1500 IU), and 0.2 cc lignocaine (2%)] weekly once. One ml of this combination was injected submucosally using a thin bore needle (size: 26 × 1½) on each side of the buccal mucosa in the regions where fibrous bands were palpable and in the retromolar regions. In addition to intralesional injection, group B patients received oral vitamin E capsules of 400 IU once daily. Patients were followed up regularly at weekly interval for a period of 8 weeks, and improvement in the patient's condition in terms of burning sensation, vesiculation/ulceration, pigmentation, paleness of mucosa, tongue protrusion, and mouth opening was monitored before, during, and after the course of the treatment, and comparison of histopathologic features was done between both the groups. The measurement of the extent of mouth opening was done before starting treatment by measuring the width in between incisal edges of the lower incisors and upper incisors. It was repeated 1 month after the treatment was started and again after the second month. Also, other findings such as, burning sensation, vesiculation/ulceration, pigmentation, paleness of mucosa, tongue protrusion, were assessed based on their presence or absence.
- Previous radio/chemotherapy.
- Subjects with systemic disorders, temporomandibular disorder, or pericoronitis.
| Results|| |
In the present study, a total of 20 OSMF patients were selected and the efficacy of intralesional dexamethasone + hyaluronidase + lignocaine (group A) was compared with dexamethasone + hyaluronidase + lignocaine + vitamin E (group B). Group B showed better reduction in burning sensation than group A [Table 1]. The groups showed equal improvement in the patient's condition in terms of vesicles and ulceration [Table 2]. Group B showed better improvement in the patient's condition in terms of pigmentation of oral mucosa [Table 3], paleness of oral mucosa [Table 4], tongue protrusion [Table 5], and extent of mouth opening [Figure 1] and [Figure 2], Graph 1 and Graph 2, and [Table 6] [Table 7] [Table 8] than group A. Also, group B showed better histopathologic improvement than group A [Figure 3] and [Figure 4], and [Table 9]. Epithelial changes did not differ significantly between the groups and dysplastic changes were not seen in both the groups.
|Figure 3: Photomicrograph showing atrophic epithelium and underlying bands of collagen with minimal inflammatory infiltrate before treatment in group B patient|
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|Figure 4: Photomicrograph (of same case) after treatment, showing atrophic epithelium and loose collagen fibers with minimal inflammatory cells with part of the epithelium showing acanthosis|
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| Discussion|| |
OSMF still remains a controversial subject regarding its pathogenesis and its management. In the present study, a total of 20 patients were studied regarding their oral mucosal features like fibrosis of oral mucosa, vesiculation or ulceration, pigmentation, and orofacial dysfunctions, such as burning sensation on taking hot and spicy foods, restricted mouth opening, and tongue protrusion. OSMF patients are graded on the basis of clinical features as follows:
Grade I (mild degree): Opening of the mouth is nearly almost normal; burning sensation on taking spicy foods; buccal mucosa shows blanching; and fibrosis present only in the posterior part of the buccal mucosa.
Grade II (moderate degree): Opening of the mouth is restricted to some extent, i.e. 2.5-3.5 cm; burning sensation on taking spicy food; buccal mucosa shows fibrous bands; and paleness of dorsum of tongue and floor of the mouth with slight restriction in tongue movement.
Grade III (severe degree): Opening of the mouth is restricted to ±2 cm; burning sensation on taking spicy food; labial and buccal mucosa, tongue, and floor of the mouth show fibrous bands; and difficulty in tongue protrusion.
In the present study, male to female ratio was 1:1 and the subjects were found to be in their second and third decades of life. Many authors, e.g. Pay Master (1956), Pindborg (1965), Akbar (1976), and Vaish (1981), found a peak incidence between third and fourth decades of life.  Age range reported in some other studies was 2-89 years. Hayes reported a rare case of OSMF in a 4-year-old Indian girl.  The onset of the disease is gradual, insidious, and often of 2-5 years duration. This could be expected owing to the fact that in early stages, the disease is not distressing to the patient. As regards its association with adverse oral habits, most of the studies have considered betel nut as the only factor for development of OSMF. However, it is difficult to state that this disease can occur in every person chewing betel nut. In the present study, the subjects had a habit of consuming pan, pan masala, betel nut, and high intake of chillies and spicy food, which is in accordance with the findings of Hayes  and Joshi. 
The formation of pale white discoloration of oral mucosa is due to epithelial atrophy, fibrosis, and constriction of blood vessels. Among the orofacial dysfunctions, restricted mouth opening along with mucosal fibrosis is the most important diagnostic feature. Inelasticity of the oral mucosa, which is responsible for the restricted mouth opening, is due to accumulation of fibrous tissue at the juxta-epithelial region. The burning sensation in the mouth of OSMF patients could be due to oral ulcers along with atrophy of the epithelium. , In the present study, the sites involved were the buccal mucosa, soft palate, uvula, lips, floor of the mouth, and tongue in descending order of frequency. These findings were in accordance with few other studies. ,,
Cases of OSMF in the present study were managed by two specific therapies: Intralesional injections of dexamethasone + hyaluronidase + lignocaine (group A) and intralesional injections of dexamethasone + hyaluronidase + lignocaine, and oral administration of vitamin E (group B). Curative response to treatment was evaluated after a period of 8 weeks. Burning sensation subsided completely in all the cases of group B, while nine cases in group A improved completely and one showed mild improvement. Vesicles and ulcers subsided in all the patients (20). While reduction/decrease in pigmentation was observed in only one patient of group B, improvement was observed in mucosa and tongue protrusion of group B patients compared to group A patients. Improvement in mouth opening was 0-5 mm in group A, whereas it was 0-16 mm in group B. Histopathologically, there was no significant change in epithelium and muscle profile between the two groups. No evidence of dysplastic changes was seen in both the groups.
Vitamin E displays no notable pharmacological effects or toxicity. It presumably prevents oxidation of essential cellular constituents. It also affords protection against various drugs, metals, and chemicals. It prevents progression of the neurological abnormalities. Large doses of vitamin E may improve the survival of erythrocytes. According to Shafer, deficiency of vitamin E has been associated with increased vascular disruption and hemolysis. Some other studies ,, on vitamin E found that vitamin E gave good results. Schwartz et al.  reported that vitamin E has been found to retard experimental carcinogenesis. Vitamin E may retard carcinogenesis by maintaining the number of Langerhans cells. Niamonitos et al. reported that vitamin E has been found to possess anti-inflammatory properties and to be an effective stimulant of the humoral immune response. Shklar et al.  found in their study that vitamin E prevents tumor formation by stimulating a potent immune response to selectively destroy cells as they begin to develop into recognizable microscopic foci of carcinoma. Gupta et al.  reported a decrease in beta-carotene and vitamin E levels, more significantly in OSMF grade II and III than in grade I. After 6 weeks of oral administration of beta-carotene and vitamin E, patients showed increase in plasma levels of these two antioxidants along with decrease in malondialdehyde (MDA) level associated with clinical improvement. Mehrotra et al.  reported that antioxidant drugs were overall favorable for early cases of OSMF clinically as well as histopathologically and they concluded that antioxidant therapy should be regularly used in cases of OSMF. In accordance with the above mentioned studies, the use of vitamin E in group B patients along with the regular intralesional injections of corticosteroids showed better results in the present study.
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.
| References|| |
Dave RP. Oral submucous fibrosis. A clinical and etiological study. J Indian Dent Assoc 1987;59:46-51.
Nair DR, Pruthy R, Pawar U, Chaturvedi P. Oral cancer: Premalignant conditions and screening - An update. J Cancer Res Ther 2012;8(Suppl 1):S57-66.
Hayes PA. Oral submucous fibrosis in a 4-year-old girl. Oral Surg Oral Med Oral Pathol 1985;59:475-8.
Joshi SG. Submucous fibrosis of the palate and pillars. Indian J Otolaryngol 1952;4:110-4.
Mani NJ, Singh B. Studies on oral submucous fibrosis. III. Epithelial changes. Oral Surg Oral Med Oral Pathol 1976;41:203-14.
Pindborg JJ, Sirsat SM. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 1966;22:764-79.
Linden GJ, McClean KM, Woodside JV, Patterson CC, Evans A, Young IS, et al
. Antioxidants and periodontitis in 60-70-year-old men. J Clin Periodontol 2009;36:843-9.
Schwartz J, Odukoya O, Stoufi E, Shklar G. Alpha tocopherol alters the distribution of Langerhans cells in DMBA-treated hamster cheek pouch epithelium. J Dent Res 1985;64:117-21.
Shklar G, Schwartz JL, Trickler DP, Reid S. Prevention of experimental cancer and immunostimulation by vitamin E (immunosurveillance). J Oral Pathol Med 1990;19:60-4.
Niamonitos C, Shklar G, Krakow AA. Effects of vitamin E dietary supplements on the exposed dental pulp in rats. Oral Surg Oral Med Oral Pathol 1985;59:627-36.
Gupta S, Reddy MV, Harinath BC. Role of oxidative stress and antioxidants in aetiopathogenesis and management of oral submucous fibrosis. Indian J Clin Biochem 2004;19:138-41.
Mehrotra R, Nigam SK, Nigam N. Role of antioxidants on oral submucous fibrosis: A clinico -pathological study. J Evolution Med Dent Sci 2013;2:9174-83.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]