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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 105-108

Nonsurgical Treatment for Oral Submucous Fibrosis: A Comprehensive Review


1 Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA
2 School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, USA

Date of Submission11-Jun-2020
Date of Decision15-Jun-2020
Date of Acceptance17-Jun-2020
Date of Web Publication06-Aug-2020

Correspondence Address:
Dr. Shaiba Sandhu
Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JIHS.JIHS_20_20

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  Abstract 


Oral submucous fibrosis (OSMF), and recently termed areca nut-induced oral fibrosis, is a debilitating disorder that hampers oral health and systemic health of patients. The management for this disorder involves a wide variety of modalities, including palliative, medicinal, and surgical. Regardless of tremendous research published in the literature, the management of OSMF has remained controversial due to the complexity of the disorder. Accordingly, this article aims to enlighten the clinicians with a comprehensive review of the current situation of the disorder and discuss the available medicinal treatment modalities for OSMF.

Keywords: Management, oral potentially malignant disorder, oral submucous fibrosis, treatment modalities


How to cite this article:
Sandhu S, Sandhu PK. Nonsurgical Treatment for Oral Submucous Fibrosis: A Comprehensive Review. J Integr Health Sci 2020;8:105-8

How to cite this URL:
Sandhu S, Sandhu PK. Nonsurgical Treatment for Oral Submucous Fibrosis: A Comprehensive Review. J Integr Health Sci [serial online] 2020 [cited 2021 Aug 4];8:105-8. Available from: https://www.jihs.in/text.asp?2020/8/2/105/291507




  Introduction Top


As the name signifies, oral submucous fibrosis (OSMF) refers to a debilitating, irreversible condition of the oral mucosa characterized by replacement of normal submucosa by bands of fibrous tissue.[1] The term OSMF was first coined by Dr. S. G. Joshi in 1953, defined by J. J. Pindborg in 1965 and, recently, clinically defined by More and Rao as “a debilitating, progressive, irreversible collagen metabolic disorder induced by chronic chewing of areca nut and its commercial preparations; affecting the oral mucosa and occasionally the pharynx and esophagus; leading to mucosal stiffness and functional morbidity; and has a potential risk of malignant transformation.”[2],[3] Chewing areca nut and various tobacco preparations such as gutkha, pan masala, and mawa have been recognized as the underlying etiological factors leading to the development of vertical fibrous bands in the buccal and labial mucosa.[4],[5] The disease burden is predominantly dispersed among the population of South and South-east Asia including countries such as India, Sri Lanka, Bangladesh, Pakistan, and China.[4],[6] Several treatment modalities have been proposed in the past 67 years since this condition was first described in the literature by Schwartz in 1952 as atrophica idiopathica mucosae oris. Till date, the most clinically accepted treatment protocol is published by More et al. The rationale of the article is to review the current situation of this disorder as well as discuss the current treatment modalities.


  Epidemiology Top


Various epidemiological studies have indicated a high prevalence of OSMF in South Asian countries due to their native ethnic, religious, and nutritional traditions favoring the disease; however, a few cases have also been noted in the non-Asian group.[7] Western immigration and globalization policies have led to changes in the epidemiology trends such that instances of OSMF are also reported in the Western countries such as the United States, Canada, the United Kingdom, and Germany.[8] According to the concerning incidence and its rapid malignant transformation rates, there is a strong need for OSMF specialist and/or dentist–scientist in Western countries to prevent this dreadful disorder and prevent patients from developing habit-related oral cancers. Population wise, most of the affected population are adults and older age patients. However, the recent study published in the literature shows an increasing incidence in children and adolescents.[9]


  Etiopathogenesis Top


Several hypotheses have been proposed to explain the etiopathogenesis of this potentially malignant oral disease. The principal causative agent is areca nut, also known as betel nut, which is a fresh or dried endosperm of the seed. This Group 1 carcinogen is chiefly used by addicts for digestion and central nervous system stimulation. The primary components of areca nut are alkaloids (arecoline, arecaidine, guvacine, and guvacoline), flavonoids (tannins and catechins), and copper, each of which contributes to the pathogenesis of OSMF.[10] The alkaloids stimulate proliferation of fibroblasts causing increased collagen formation. On the other hand, flavonoids increase the activity of lysyl oxidase (LOX), an enzyme which leads to increased collagen crosslinking, thereby making collagen resistant to proteolysis.[11] Copper which is found in high amounts in areca nut also upregulates the enzyme LOX, adding to the process of oral fibrosis. Other potential supplemental etiological factors are nutritional deficiencies (especially iron, Vitamin B complex, and protein), genetic predisposition (increased frequency of human leukocyte antigen 10, DR3, and DR7 in OSMF), and molecular mechanisms (cytokines and growth factors)[8] [Figure 1].
Figure 1: Etiopathogenesis of oral submucous fibrosis

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  Clinical Manifestations and Diagnosis Top


OSMF is primarily present in middle-aged people with a peak incidence in the second to the fourth decade of life. The gender predilection varies geographically, but it has been found to be more prevalent in males as compared to females with a ratio of 6:1.[10] The most commonly affected sites are buccal mucosa, retromolar area, soft palate followed by faucial pillars, labial mucosa, tongue, the floor of mouth, lips, and gingiva. Patients most often present with the chief complaint of limited mouth opening associated with oral burning sensation. Blanched oral mucosa, vesicles, petechiae, sparse brownish-black pigmentation, and the presence of palpable fibrous bands are some of the initial signs which can be appreciated.[10],[12] As the disease becomes advanced, there is progressive rigidity of submucosal tissues such that the mucosa acquires a mottled or white marble-like appearance.[11] When the uvula is involved, it gets shrunken and undergoes alteration in shape (inverted, bud-like, and deviated).[11] Due to increased fibrosis, the tongue becomes immobile, and there may be associated depapillation, defective gustatory, and taste sensation. The extraoral manifestations include prominent malar bones with sunken cheek, thinning of lips, increase in philtrum area, loss of nasolabial fold, and ellipsoid and limited mouth opening. Hearing impairment can also result because of stenosis of the  Eustachian tube More Details. When the inter-incisal distance is <5 mm, it is considered severe OSMF, and fibrous ankylosis can be observed sometimes in these cases. The diagnosis of OSMF is based on the above-described clinical signs and symptoms.[10]


  Medicinal Treatment Modalities Top


OSMF is a progressive disease which does not regress after the cessation of chewing areca nut. The management varies widely among clinicians. The commonly employed medicinal treatment modalities have been included in this review.

Nutritional supplementation and antioxidants

Supplementation with Vitamin A (50,000 IU), beta-carotene (10–20 mg), Vitamin E (400 mg), or lycopene (8 mg) once daily, has been widely used as the first-line treatment in all stages of OSMF, primarily owing to the antioxidant activity.[11] Due to the anti-inflammatory and immunosuppressive A herbal supplement, Curcumin, which is a compound found in turmeric, has also been used in the management of OSMF. Curcumin possesses potent antioxidant, antimicrobial, pro-apoptotic, anti-inflammatory, and anti-fibrotic functions.[11] It is prescribed in the form of 300 mg tablet to be taken once daily for a period of 6–8 months. As OSMF has been linked to nutritional deficiencies, supplementation with ferrous ascorbate (100 mg), folic acid (1.5 mg), and zinc sulfate (220 mg) has been recommended in some treatment protocols.[11]

Fibrinolytics and vasodilators

Hyaluronidase

As increased fibrosis is the underlying pathogenesis of OSMF, hyaluronidase which breaks down hyaluronic acid lowers the viscosity of intercellular matrix and causes dissolution of the fibrotic bands, which can be beneficial for patients with restricted mouth opening.

Interferon gamma

Interferon gamma is an antifibrotic agent which reduces the proliferation of fibroblasts and as a result suppresses the collagen synthesis. Additionally, it increases the synthesis of antifibrotic cytokine and collagenase. More et al. advocated intra-lesional injection of interferon gamma (50 mg) twice a week for 8–10 weeks in patients with mouth opening <25 mm.[11]

Pentoxifylline

Pentoxifylline is a methylxanthine derivative that exerts an anti-tumor necrosis factor alpha effect, increases erythrocyte flexibility, dilates blood vessels, inhibits inflammatory reactions, decreases proliferation of fibroblasts and the production of extracellular matrix, and increases collagenase activity; therefore, it is useful in the treatment of OSMF. Pentoxifylline 400 mg is prescribed to be taken three times daily for 4–6 months only for patients with mouth opening <15 mm.[11]

Isoxsuprine

Isoxsuprine is a beta 2 agonist which causes vasodilation. It also inhibits platelet aggregation and, as a result, reduces blood viscosity. Isoxsuprine 10 mg QID for 6 days is recommended for patients with mouth restriction of <15 mm.[11]

Immunomodulators

Corticosteroids

Corticosteroids have potent anti-inflammatory and immunosuppressive effects due to which topical and intra-lesional steroids are widely indicated for the management of OSMF. More et al. recommended two regimens of intralesional injection – the first regimen is an injection of the mixture of dexamethasone (4 mg) + placental extract (2 ml) + chymotrypsin (5000 IU). The second regimen is an injection of the mixture of dexamethasone (4 mg) + hyaluronidase (1500 IU) + chymotrypsin (5000 IU) two injections per week for the treatment of patients with mouth opening <35 mm.[11]

Levamisole

Levamisole (50 mg tablet), an immunomodulator which modifies both the humoral and cell-mediated immunity, can be used for the management of patients with severe OSMF. However, on extended therapy, leukopenia and agranulocytosis could develop.

Placental extract

Placental extract (2 ml) acts as a biogenic simulator which has growth factors and anti-inflammatory substances.[7] It also increases tissue vascularity. Katharia reported significant improvement in mouth opening with the administration of placenta extract.[13]

Palliative and physiotherapy

In addition to the medicinal treatment, discontinuation of habit and consumption of red fruits and green leafy vegetables is the most common practice. Physiotherapy exercises, especially ballooning technique, blowing of mouth, and opening and closing of the mouth are also the common recommendations to increase the mouth opening, however, the magnitude varies per the severity of the disorder.[14],[15],[16],[17]


  Conclusion Top


OSMF is a dreadful and complex disorder which requires serious attention from both diagnostic and management standpoint. According to the management standpoint, more clinical trials and observational studies on new potential drugs are the need of the hour to improve patient's quality of life. Moreover, the management of this disorder can have a better outcome if a multi-professional approach is practiced. Additionally, local and national government bodies should take steps to educate the population to prevent any oral potentially malignant disorders and oral cancer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Pindborg JJ, Sirsat SM. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 1966;22:764-79.  Back to cited text no. 1
    
2.
Joshi SG. Fibrosis of the palate and pillars. Indian J Otolaryngol 1952;4:1-4.  Back to cited text no. 2
    
3.
More CB, Rao NR. Proposed clinical definition for oral submucous fibrosis. J Oral Biol Craniofac Res 2019;9:311-4.  Back to cited text no. 3
    
4.
Rao NR, More CB, Brahmbhatt RM, Chen Y, Ming WK. Causal inference and directed acyclic graph: An epidemiological concept much needed for oral submucous fibrosis. J Oral Biol Craniofac Res 2020; doi.org/10.1016/j.jobcr.2020.06.008.  Back to cited text no. 4
    
5.
More CB, Rao NR, More S, Johnson NW. Reasons for Initiation of Areca Nut and Related Products in Patients with Oral Submucous Fibrosis within an Endemic Area in Gujarat, India. Subst Use Misuse 2020;55:1413-21.  Back to cited text no. 5
    
6.
More C, Peter R, Nishma G, Chen Y, Rao N. Association of Candida species with oral submucous fibrosis and oral leukoplakia: A case control study. Ann Clin Lab Res 2018;6:248.  Back to cited text no. 6
    
7.
More C, Shah P, Rao N, Pawar R. Oral submucous fibrosis: An overview with evidence based management. Int J Oral Health Sci Adv 2015;3:40-9.  Back to cited text no. 7
    
8.
Pindborg JJ, Bhonsle RB, Murti PR, Gupta PC, Daftary DK, Mehta FS. Incidence and early forms of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 1980;50:40-4.  Back to cited text no. 8
    
9.
More CB, Rao NR, Hegde R, Brahmbhatt RM, Shrestha A, Kumar G. Oral submucous fibrosis in children and adolescents: Analysis of 36 cases. J Indian Soc Pedod Prev Dent 2020;38:190-9.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
More C, Shilu K, Gavli N, Rao NR. Etiopathogenesis and clinical manifestations of oral submucous fibrosis, a potentially malignant disorder: An update. Int J Curr Res 2018;10:71816-820.  Back to cited text no. 10
    
11.
More CB, Gavli N, Chen Y, Rao NR. A novel clinical protocol for therapeutic intervention in oral submucous fibrosis: An evidence based approach. J Oral Maxillofac Pathol 2018;22:382-91.  Back to cited text no. 11
[PUBMED]  [Full text]  
12.
More C, Pawar R, Rao N, Shah P, Gavli N. Oral ulcer: An overview with an emphasis on differential diagnosis. Int J Oral Health Sci Adv 2015;3:1-3.  Back to cited text no. 12
    
13.
Katharia SK. The effects of placenta extract in management of OSMF. Indian J Pharmacol 1992;24:181-3.  Back to cited text no. 13
  [Full text]  
14.
Rao NR, Villa A, More CB, Jayasinghe RD, Kerr AR, Johnson NW. Oral submucous fibrosis: A contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management. J Otolaryngol Head Neck Surg 2020;49:3.  Back to cited text no. 14
    
15.
Hazarey VK, Erlewad DM, Mundhe KA, Ughade SN. Oral submucous fibrosis: Study of 1000 cases from Central India. J Oral Pathol Med 2007;36:12-7.  Back to cited text no. 15
    
16.
Kumar A, Bagewadi A, Keluskar V, Singh M. Efficacy of lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:207-13.  Back to cited text no. 16
    
17.
Selvam N, Dayanand A. Lycopene in the management of oral submucous fibrosis. Asian J Pham Clin Res 2013;6:58-61.  Back to cited text no. 17
    


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