A Longitudinal Study of the Effect of Placental Extract in the Treatment of Moderate and Moderately Advanced Oral Submucous Fibrosis

INTRODUCTION

Oral Submucous Fibrosis (OSF) is an insidious chronic disease affecting any part of the oral cavity and sometimes pharynx.¹ This disease is thought to be caused due to the use of areca nut chewing, although other factors like spicy food, genetic mutation and nutritional deficiencies are suspected.^2-6 Use of areca nut produces progressive hyalinization of the lamina propria and induces juxtaepithelial inflammatory reaction⁷. This leads to stiffness of the oral mucosa leading to progressive limitation in opening of the mouth and protrusion of the tongue⁸. It is considered as a premalignant lesion with malignant transformation rate ranging from 2.3 to 7.6% over a 10 year period.^9-12

OSF is treated conservatively by medication that can be delivered systemically, topically or intralesionally. Local intralesional injections of corticosteroids, hyaluronidase, IFN-gamma and placental extracts have all been tried with variable improvements in the condition.

Aqueous solution of human placenta (placental extract) is a promising agent in reducing fibrotic bands as well as juxta epithelial inflammatory reaction.^13-15 Placental extract is produced from enriched fresh human healthy placenta which contains nucleotides, amino acids, peptides, fibroblast growth factors and vitamins in natural form. Placental extract reduces inflammation and promotes wound healing property by increasing blood circulation and tissue vascularity. It also acts as a biogenous stimulator, by accelerating cellular metabolism and stimulating regenerative process^{16, 17}. Various studies have shown the clinical effectiveness of placental extract injection in reducing the fibrosis in OSF.

The present study was conducted to evaluate the effectiveness of sub mucosal injection of placental extract in the treatment of moderate and moderately advanced OSF.

MATERIALS AND METHODS

A Longitudinal Study was conducted in KVG Dental College and Hospital, Sullia. Patients reporting to the department of Oral Medicine and Radiology who were clinically diagnosed to have moderate & moderately advanced OSF were selected by purposive sampling method. Patients with systemic disorders, those having accompanied deleterious habits like alcoholism and smoking and those who refused to undergo the treatment were excluded from the study.  

Among 118 clinically diagnosed OSF patients, 24 patients constituted the study group. Informed consent was obtained from all the patients. A detailed history about their habit index was obtained and a systematic clinical examination was performed. Following the clinical diagnosis of OSF, patients were subjected to incisional biopsy procedure for the histological confirmation of the premalignant condition. The treatment protocol was explained to them in their local language before commencement of the study. They were then categorized into two groups: Group A and Group B based on the amount of their mouth opening before the initiation of the treatment. The criteria for the grouping is modified from 18 the classification of OSF by Khanna and Andreade. Group A consisted of 12 patients with inter - incisal mouth opening of less than 25mm (moderately advanced OSF). Group B consisted of 12 patients with inter - incisal mouth opening between 26 to30 mm (moderate OSF). Patients of both the groups received the same treatment.

Each patient was given 2 ml of placental extract sub mucosal injection alternatively on right and left buccal mucosa once a week for a total period of 10 weeks. Injection is given at the maximum area of fibrosis, by inserting the needle parallel to the mucosa and delivering the drug while withdrawing the needle. Clinical improvement was evaluated during their next visit for the treatment. Two clinical parameters were considered during the evaluation: a) increase in inter incisal mouth opening measured in millimeter; b) reduction in the burning sensation measured by visual analogue scale. Both the parameters were measured and recorded systematically. Adverse reaction to the drug during the treatment period was also recorded.

RESULTS

Twenty four patients who were clinically and histologically diagnosed as having OSF were selected for the study. Detailed case history was obtained from all the patients. All the patients had areca nut chewing habit for a varying period of time. 12 patients had moderately advanced fibrosis with mouth opening of less than 25mm and 12 patients had moderate fibrosis with mouth opening ranging 26-30mm (Table 1). Ten weeks post treatment measurements revealed improved mouth opening in both the groups; yet the degree was more pronounced in the patients with moderate fibrosis with a mean improvement of 6.16mm (Graph 1).

During the study, it was incidentally observed that there was a difference in the treatment outcome between younger and older age groups. So the patients were grouped according to their age into two categories: First group of patients below 35 years (mean: 27 years) and second group of patients with age above 35 years (mean: 47 years). Average initial mouth opening in first group was 25 mm. After treatment their mouth opening increased to 31.25 mm, with an average increase of 6.25 mm. Average initial mouth opening in second group was 25 mm. After 10 doses of placental extract injection, mouth opening increased to 29.5 mm with an average increase of 4.5 mm (Graph 2).

DISCUSSION

OSF is a known potentially malignant disorder of the oral cavity. Areca nut has been considered as the main causative agent for OSF^{2-6, 12, 19-21} though other factors like capsaicin²², tobacco²³, spicy foods²⁴ and alcohol⁸ are known to substantially contribute to the disease. All the patients in this study were positive for arecanut chewing habit. This finding stresses the role of arecanut in the development of OSF. Sirat and Pindborg believe that mucosal ulcerations and palatal blisters are the early clinical symptoms of the disease.^7,24 Dryness of the mouth would also be experienced by some patients during the initial stage.²⁵ All the patients in the present study had moderate to severe burning sensation while having spicy food. 20% of the patients gave a positive history of blister formation. Out of 24 patients, 13 had fibrosis on left buccal mucosa and 7 had on the right side. Only 4 patients exhibited bilaterally symmetrical fibrosis. Pindborg is of the openion that there will be symmetrical fibrosis in OSF^24,26. The difference seen in the present study may be due to the unilateral areca nut quid keeping habit of patients.

All the patients had moderate to severe burning sensation during their first visit. After treatment, patients experienced reduction in severity of burning sensation; with occurrence of mild burning sensation while having spicy food. This indicates the effectiveness of placental extract in reducing burning sensation.

Patients in the study were divided into 2 groups based on the severity of fibrosis for comparison on effectiveness of the treatment. Patients with moderately advanced fibrosis formed Group A, whereas Group B consisted of patients with moderate fibrosis. Average initial mouth opening of the Group A patients was 22.5 mm. After 10 doses of placental extract injection, the inter incisal opening increased to 27 mm with average increase of 4.5 mm. In the Group B, average initial mouth opening was 27.5 mm. The inter incisal mouth opening improved to 33.8 mm post treatment with an average increase of 6.3 mm. This shows that the treatment of OSF with placental extract injection is more effective in moderate fibrosis compared to the moderately advanced fibrosis (Graph 1).

On observing the patients' response to treatment from the perspective of their age, it was noticed that patients under 35 years (mean: 27 years) demonstrated greater degree of mouth opening after treatment than for the patients over 35years. On analysis, patients under 35years had an average increase in the mouth opening of 6.25mm whereas patients over 35years experienced 4.5mm of average mouth opening.

An evaluation was made about the complications during the treatment. All the patients experienced moderate to severe pain during the injection of placental extract and a diffuse swelling at the site on the following day. No other complications were observed on any of the patients during the treatment period.

CONCLUSION

Sub mucosal injection of placental extract is an effective treatment modality for OSF. It is efficient in alleviating burning sensation also. Its action is pronounced in young patients with mild to moderate fibrosis than with severe fibrosis.

ACKNOWLEDGEMENT

We thank Rajiv Gandhi University of Health Sciences, Karnataka for the financial support of this study.