Abstract
In a country such as India, popularly known for its rich diversity and traditions, chewing tobacco and its many other forms is a commonly practised entity. The resultant of this leads to oral submucous fibrosis (OSMF) which causes permanent morbidity in the form of trismus and also can lead to potential possibility of oral cancer. Intra oral injections of steroids such as hyaluronidase and placentrex have been postulated by many studies. But this study was done to evaluate the efficacy of both these commonly used treatment modalities. A 1 year hospital based study was performed over 30 patients diagnosed to be having oral submucosal fibrosis. They were randomly given injection hyaluronidase and injection placentrex. In addition to this, routine haemogram was done and the inter incisor distance was measured before and after the treatment along with histopathological study of the oral lesions. With a prevalence of 0.31%, the males out numbered females. Majority of the patients were in their third decade. All patients chewed tobacco in one or the other form and 90% of them presented with burning sensation in the mouth. The mean inter incisor distance in our patients was 3.1%. A third of the cases were anaemic and two thirds had an elevated erythrocyte sedimentation rate and serum globulin level. More than half the cases had an elevated absolute eosinophil count. All 30 biopsy specimens showed atrophic oral mucosa with subepithelial dense collagenised fibrous tissue. The group of patients who were treated with injection placentrex showed slightly better results than corticosteroids. The results were not statistically significant although clinically they were noteworthy. Being a silent, chronic disease, oral submucosal fibrosis affects the most productive population fraction of our country causing morbidity and also acts as precursor for oral cancer. Since the etiological agent is chewing areacnut in one form or the other, considerable efforts have to be made in sensitizing the workforce of the nation at the community level in understanding the ill effects of chewing tobacco. Understanding the associated conditions such as anaemia, elevated erythrocyte sedimentation rate, serum globulins and absolute eosinophil count should prompt the otolaryngologist in treating these patients holistically. Though injection placentrex yielded better improvement in the inter incisor distance, the results with steroid injection was also comparable with no statistical significance. Hence, keeping the premalignant nature of the disease, screening the patients promptly and treating them on time would lead to considerable reduction in the morbidity caused by the disease. Coupled with health education, the results could be even more encouraging.
Keywords: Arecanut, Oral submucosal fibrosis, Placentrex, Hyaluronidase, Inter incisor distance
Introduction
Human beings are subjected to stress and tension in this century due to growing fast industrialization and civilization. Most of them fall into the tension relieving habits like smoking, alcoholism, pan, tobacco or betel nut chewing. These habits not only relieve tension to some extent but also produce bad effects on human body apart from being addictive. Oral submucous fibrosis (OSMF) is one of the conditions resulting from these tension relieving habits.
Oral submucous fibrosis has been well established in Indian medical literature since the time of Sushruta. In the modern literature it was first described by Schwartz [1]. In India, Joshi (1953) was the first to describe the condition and he called the condition “submucous fibrosis of the palate and pillars” [2].
Oral submucous fibrosis is an insidious chronic disease of unknown etiology affecting the mucosa of any part of the oral cavity and occasionally extending to pharynx and oesophagus and rarely to larynx. The condition is some times preceded by and or associated with vesicle formation but always associated with juxta epithelial inflammatory reaction followed by a fibro elastic change of the lamina propria with epithelial atrophy leading to stiffness of the oral mucosa causing trismus and inability to eat [3, 4]. Thus patients do not enjoy food in OSMF.
OSMF predisposes a patient to develop oral cancer. The most vulnerable people are Asians and amongst them, predominantly Indians [3, 5]. If the habit of betel chewing, smoking and alcohol are not relieved, then there is an increase in the probability of developing leukoplakia and squamous cell carcinoma [6]. Most commonly males are the victims of this disease owing to the higher prevalence of the above mentioned habits in them [7].
Owing to the immunosuppressive and anti-inflammatory properties of steroids and the hormonal and bio—moulding capacity of placentrex, this study was done to understand the role of these two agents in the management of OSMF.
Objective
To study the effectiveness of intraoral submucosal injections of corticosteroids and placentrex in the management of OSMF.
Materials and Methods
This study was carried out in The Department of ENT, KLES Dr Prabhakar Kore Hospital and MRC, Belgaum.
Study design: prospective study.
Study period: 1 year from October 2005 to October 2006.
Sample size: 30.
Inclusion criteria: all patients with history of burning sensation in the mouth on eating hot and spicy food with trismus on examination and presence of blanching of the oral mucosa with presence of fibrotic bands.
Exclusion criteria: all patients having < 2 cm trismus were excluded. Patients having pale oral mucosa secondary to anemia. In addition to this, patients who have already undergone oral surgeries in the past and those patients giving history of consumption of caustics were excluded.
Methodology: every patient of OSMF attending the ENT out patient department was subjected to a detailed examination. The lips, labial mucosa, buccal mucosa, gingiva, tongue, floor of mouth and palate were examined. Additionally, to assess trismus, the inter incisor distance was measured with the help of callipers and recorded as follows:
More than 3.5 cm.
3–3.5 cm.
2–3 cm.
All the patients were subjected to hematological investigations to assess the hemoglobin percentage (Hb%), Erythocyte sedimentation rate (ESR), absolute eosinophil count (AEC) and serum globulin (gm%).
Biopsy: biopsy was taken from the site of clinically noticeable fibrous bands using a Luc’s forceps under the effect of 4% topical xylocaine anaesthesia.
The 30 patients were randomly put on either injectable corticosteroid (triamcinolone) 40 mg along with 1500 IU hyaluronidase or injectable placentrex 2 ml submucosal injection biweekly for a period of 8 weeks with a follow up period of 4 months.
Results
In our study, the prevalence of OSMF was 3.10 per 1000 patient population (0.31%). The youngest patient was aged 18 years. The oldest was 53 years. The maximum number of cases (13 out of 30) were in the third decade forming 43%. This was followed by nine cases in their second decade accounting for 30%. 80% of the patients in the present study were males.
Out of 30 cases, 23 (76.7%) were in the habit of eating pan masala. 17 (56.7%) were in the habit of eating only pan masala and 6 (20%) were in the habit of eating pan masala with betel nut and tobacco as seen in Table 1. The duration of chewing habits varied from minimum of 3 months to maximum of 31 years. Maximum number of patients that is 20 (7%) were into the habit for more than 2 years and about 23% were in the range of chewing since 1–2 years.
Table 1.
Type of chewing habits
| Habit | No. of cases | Percentage |
|---|---|---|
| Pan masala | 17 | 56.7 |
| Betelnut (B.N) | 2 | 6.7 |
| Tobacco (T) | 1 | 3.3 |
| Pan masala + B.N | 1 | 3.3 |
| Pan masala + tobacco | 2 | 6.7 |
| Pan masala + BN + T | 3 | 10 |
| Betelnut + tobacco | 4 | 13.3 |
| Total | 30 | 100 |
Further, 57% of the patients had the habit of chewing 1–5 times in a day as opposed to 20% who were chewing more that 10 times in a day. The chief complaints of the patients in our study constituted of burning sensation in the mouth, difficulty in mouth opening and impaired taste as seen in Fig. 1. Our patients presented with more than one chief complaint out of which burning sensation was the commonest. It was present in 27 patients forming 90% of the total. The next common complaint was difficulty in mouth opening which was observed in 20 patients. Fourteen patients had impaired taste. The time duration between onset of symptoms and presentation to hospital was variable. The minimum was 1 month and maximum was 3 years as shown in Table 2.
Fig. 1.
Graph showing symptomatology
Table 2.
Duration of symptoms
| Duration (months) | No. of cases | Percentage |
|---|---|---|
| 0–6 | 11 | 37 |
| 7–12 | 10 | 33 |
| 12–24 | 7 | 23 |
| > 24 | 2 | 7 |
| Total | 30 | 100 |
The inter incisor distance was measured using calipers (Fig. 2) in all our patients for the purpose of grading the trismus. It was grouped into four categories as proposed by Lai (1995) [7]:
Group A: > 35 mm
Group B: between 30 and 35 mm
Group C: between 20 and 30 mm
Group D: < 20 mm
Fig. 2.
Image showing measurement of inter-incisor distance using slide calipers
Out of the total 30 patients we had in our study, 1 (3%) belonged to Group A. There were 14 (47%) and 15 (50%) patients who belonged to Group B and C respectively. The mean inter incisor distance in our patients was 3.1 cm. The maximum and the minimum inter incisor distance of the patients in our study was 4 cm and 2 cm respectively.
The mean hemoglobin percentage in our patients was 11.6 gm%. 10 (33%) patients had hemoglobin percentage less than 10 gm%. The rest 20 (67%) had a hemoglobin percentage above 10 gm%. We had estimated the erythrocyte sedimentation rate of all the patients in our study. The patients were then categorized into two categories as those having erythrocyte sedimentation rate below 20 mm/1st hour and those having erythrocyte sedimentation rate above 20 mm/1st hour. We had 11 (37%) patients in the first category. The rest 19 (63%) patients were in the second category. The mean erythrocyte sedimentation rate in our study was 27 mm/1st hour.
Out of 30 cases, 17 (57%) showed AEC > 400 cells/cmm and 13 (43%) showed AEC < 400. maximum being 700 cells/cumm and minimum being 100 cells/cumm. Serum globulin level was within 2.5 gm% in 10 (33%) cases and was raised above 2.5 gm% in 20 (67%) cases.
Histopathological examination of the biopsy specimens of all the cases showed atrophic oral mucosa. Subepithelial areas showed dense collagenised fibrous tissue.
Out of the 30 cases diagnosed as OSMF, 15 were treated with corticosteroids (triamcinolone) 40 mg along with hylase 1500 IU and 15 patients received 2 ml placentrex. The mean interincisor distance of patients who were treated with corticosteroids along with hylase before and after was 2.85 cm and 3.27 cm respectively showing a marked improvement of 12%, whereas for placentrex the inter incisor distance was 3 cm and 3.64 cm respectively showing an improvement of 18% which was statistically not significant but clinically significant as seen in Table 3.
Table 3.
Comparison between the different treatment modalities used
| Treatment modality (injections) | No. of cases | Average I.I.D. before treatment | Average I.I.D. after treatment | Mean improvement | Percentage of improvement |
|---|---|---|---|---|---|
| Corticosteroid + hyaluronidase | 15 | 2.85 | 3.27 | 0.42 | 12.84 |
| Placentrex | 15 | 3.00 | 3.64 | 0.64 | 17.58 |
I.I.D inter incisor distance
Discussion
The prevalence of OSMF in our study was 0.31%. A study conducted by Pindborg et al. (1968) reported prevalence rate upto 0.4% in Indian rural populations [8]. According to Pandya et al., a 0.2–0.5% prevalence is present in India [9]. Since ours is a hospital based study, the values are those measure among the patient population only and thus the true prevalence in the community is bound to be higher. Maximum cases were in the third decade. Borle and Borle (1991) reviewed 326 cases over a period of 7 years and found that majority of the patients were in the third decade with a peak inidence at 20–25 years [10]. The same was also documented by Khanna and Andrade (1995) wherein 100 patients were studies and a peak incidence was documented in the age group of 20–30 years respectively [11].
Male predominance in OSMF as in our study was also observed by Khanna and Andrade (1995) wherein the male:female ratio was 2.1:1 [11]. Lai et al. (1995) in their study of 150 cases reported a male:female ratio of 29:1 [7]. In the present study the maximum number of patients were in the habit of chewing betel nut in one or the other form. The same etiology has been stressed in the study done by Murti et al. in 1995 wherein 275 patients were studied over a period of 5 years [12]. Their study involved assessing the results of several studies done in India, Pakistan and South Africa. Areca nut emerged as the most frequently used substance for chewing. This was also reiterated by the study done by Canniff et al. (1986) where almost 100% of patients were involved in tobacco chewing [13].
The duration of chewing habits varied from minimum of 3 months to maximum of 31 years. Most of our patients i.e. 20 (67%) were chewing for more than 2 years. This was followed by 23% patients who chewed for a range between 1 and 2 years. Canniff et al. (1986) reported chewing habits ranging from 1 to 46 years in their study [13]. This was also stressed upon by Seedat et al. wherein the duration of chewing ranged from a few months to over 70 years [6]. The same author also found that majority of their study subjects chewed tobacco less than five times in a day as observed in our study as well.
Burning sensation in the mouth and difficulty in opening mouth were the most routinely observed symptom which was also seen in the works of Gupta et al. (1980) and Canniff et al. (1986) [4, 13]. Our patients presented with more than one chief complaint. Burning sensation was the commonest chief complaint. Few patients also complained of impaired taste which could be perhaps due to loss of lingual papillae. The time duration between onset of symptoms and presentation to hospital was variable. The minimum was 1 month and maximum was 3 years. Canniff et al. (1986) reported that the symptoms ranged 6 months to 20 years [13]. This indicates that OSMF undergoes a very slow progression and hence many of the patients learn to cope up with the morbidity caused by the disease and avoid presentation to the hospital.
There were ten (33%) patients having hemoglobin percentage less than 10 gm%. Canniff et al. (1994) found hemoglobin concentration below 11.5 gm% in 30% of his cases [13]. Khanna et al. (1995) found hemoglobin concentration below 10 gm% in 40% of his cases [11]. All the 30 specimens were subjected to histopathological examination. Atrophic oral mucosa with subepithelial areas showing dense collagenised fibrous tissue was present. There was absence of malignant transformation. Our findings are in agreement with the works of Gupta et al. (1980) [4]. Also a correlation between the clinical and histopathological findings could not be established. According to Kiran Kumar et al., the fibrosis in later stages of OSMF could be explained due to more collagen bands being formed in the posterior region thus leading to trismus eventually [14]. Also the inflammatory mediators were inconsistent with respect to the duration of the disease with lesser number in the chronic phase probably due to stabilisation of the lesion causing a reduction in the number and function of pro-inflammatory mediators. In the series by Khanna and Andrade, all the patients were subjected to a routine haemogram but there was no comment on the prevalence of anaemia [11]. But the role of anaemia in chronic diseases cannot be over looked and probably should also raise concerns about its prompt evaluation and early correction inorder to achieve better symptomatic relief and early resolution of the histopathologic changes and thus probably preventing progression into malignancy.
Majority of our patients (63%) had an elevated erythrocyte sedimentation rate (ESR). Khanna et al. (1995) in their works have also highlighted the same in 86% of their patients [11]. This probably hints to the chronicity of the disease. Coupled with the co-existing anemia that is seen in most of the patients, an elevated ESR can also be explained by a reduced haemoglobin.
57% of our patients had an elevated absolute eosinophil count (AEC). This supports the allergic response found in OSMF. Similar findings have been stressed upon in the works of Bailoor et al. (1993) [15]. Nearly two-thirds of our patients had an elevated serum globulin (> 2.5 g%) which was also observed in study done by Phatak (1978) wherein the reported globulin levels were 3.79 ± 0.72 gm% [16]. This fact may hint towards the theory of autoimmunity for OSMF in our locality where the study was conducted.
The mean inter incisor distance of patients who were treated with corticosteroids along with hylase before and after showed a marked improvement of 12%, whereas for placentrex, the improvement was 18% which was statistically not significant but clinically significant.
Since the above two treatment modalities are statistically insignificant both the two are equally efficacious but clinically the improvement of symptoms were slightly more with the use of placentrex. Since placentrex showed better results, it being cheaper and safe can be preferred over corticosteroid treatment modality. Sinha et al. (1978) treated 36 patients of OSMF [17]. They concluded that hydrocortisone is superior to placentrex in the treatment of OSMF. Ramanjaneyulu et al. (1980) treated ten patients mostly belonging to the middle age group with local injection of placentrex once a week for 10 weeks and concluded that placentrex was safe, cheap, effective and could be used without any side effects [18]. Kakar et al. (1985) tried 4 regimens of treatment in 96 patients, by dividing at random into 4 groups of 24 each. They recommended local injections of combination of dexamethasone and hyaluronidase to achieve quicker and maximal improvement [19]. Deepak Gupta et al. (1988) recommended a course of local injections consisting of combination of dexamethasone, hyaluronidase and chymotrypsin biweekly for 10 weeks [4]. Hence, there is no clear cut evidence of one treatment modality being superior to the other. However in our study, patients who received placentrex injection faired better compared to those who received hyaluronidase.
Conclusions
In a land of unique diversity with a number of varied cultures, traditions and religion; Indians easily fall into the life threatening evil effects of smoking, alcohol, tobacco chewing, pan and areca nut chewing. These are easily picked up from customs and traditions, parents, friends and also due to the influence of social media on the youngsters. Often, people tend to carry these evils as a symbol of status and in few areas offering these implies hospitality and equality.
Oral submucous fibrosis being a silent ailment can affect people from the younger age groups itself. As arecanut has been identified as an etiologic agent, it is amenable to primary prevention. The preventive measures should be in the form of curbing the use of arecanut products, including those without tobacco through public awareness and education.
Our study results concluded that both steroid injections and placentrex injection have been equally effective with no statistical differences. But it has been proven by this study that both the modalities significantly cause an improvement in halting the progression of the disease and regression of the symptoms.
Funding
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Code Availability
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Compliance with Ethical Standards
Conflict of interest
All authors declare that they have no conflict of interest.
Ethical Approval
Approval was obtained from the ethics committee of KLE Academy of Higher Education and Research (formerly KLE University). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.
Human and Animal Rights Participants Statement
The authors affirm that human research participants provided informed consent for publication of the images.
Informed Consent
Written informed consent was obtained from each study participant.
Footnotes
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