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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists


 
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REVIEW ARTICLE  
Year : 2018  |  Volume : 22  |  Issue : 3  |  Page : 382-391
 

A novel clinical protocol for therapeutic intervention in oral submucous fibrosis: An evidence based approach


1 Department of Oral Medicine and Maxillofacial Radiology, K.M. Shah Dental College and Hospital, Sumandeep Vidyapeeth University, Vadodara, Gujarat, India
2 Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing, China; Harvard Medical School, Boston, MA, USA
3 Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA

Date of Submission04-Sep-2018
Date of Acceptance06-Sep-2018
Date of Web Publication14-Dec-2018

Correspondence Address:
Chandramani Bhagwan More
Department of Oral Medicine and Maxillofacial Radiology, K.M. Shah Dental College and Hospital, Sumandeep Vidyapeeth University, Piparia, Vadodara, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jomfp.JOMFP_223_18

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   Abstract 


Oral submucous fibrosis (OSMF) is a chronic, progressive, debilitating, scarring and crippling disorder of the oral cavity. It is a potentially malignant oral disease which predominantly affects people of South and Southeast Asia, especially Indian subcontinent, where chewing of areca nut and its commercial preparation is rampant. However, due to increase in immigration of people from the Indian subcontinent, the health professionals in many developed countries do come across this disease very often. Since decades, many treatment modalities are suggested and studied using medicines, surgery and physiotherapy, with varying degrees of benefit, but none have been able to cure this disease completely, and hence, it has become a challenging condition. The present article emphasizes on various therapeutic interventions used till date to curb the menace of this disease and the principal author with his vast academic research and clinical experience in treating this disease has proposed the stage-wise treatment regimen for OSMF. The current article is an attempt to compile the available treatment, its current status and future perspectives, so as to assist early intervention of the disease with evidence-based approach. This article will ignite the research minds of dental clinician, oral medicine specialist, otolaryngologist and general physician in treating OSMF.


Keywords: Areca nut, evidence-based treatment, oral submucous fibrosis, protocol, therapeutic interventions, tobacco


How to cite this article:
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

How to cite this URL:
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 [serial online] 2018 [cited 2019 Jan 20];22:382-91. Available from: http://www.jomfp.in/text.asp?2018/22/3/382/242760





   Introduction Top


Oral cavity is rightly described as mirror of the body as it reflects the health of the individual. Oral mucosa is a unique tissue, lined by keratinized and nonkeratinized stratified squamous epithelium and underlying connective tissue (lamina propria). The oral mucosa is continuously exposed to chemicals, microorganisms, thermal changes and mechanical irritants (tobacco, areca nut, alcohol, etc). The epithelial and connective tissue components of the oral mucosa demonstrate acute and chronic reactive changes in response to the above stressors.[1],[2] The keratinized epithelium which is present on the dorsum of the tongue, such as hard palate and attached gingiva, shows less reactive changes to the stressors as compared to the nonkeratinized epithelium, which is seen everywhere in the oral cavity including the buccal mucosa, labial mucosa, alveolar mucosa and specialized mucosa. Changes indicative of disease are seen as alterations in the oral mucosal lining.[2],[3],[4],[5],[6]

Oral submucous fibrosis (OSMF) is a chronic, insidious, progressive, debilitating, scarring, irreversible, complex and crippling disorder of the oral cavity.[4],[5],[6],[7],[8] This oral potentially malignant disorder (OPMD) a collagen disorder was first described as early as 600 BC by Sushruta, the renowned Indian physician, as Vidari. Schwartz in 1952 after observing similar features in five Indian women of Kenya described this condition as progressive inability to open the mouth due to loss of elasticity and development of vertical fibrous bands in the labial and buccal tissues. He termed it as atrophia idiopathica mucosae oris. In 1953, Dr. S.G. Joshi coined the term OSMF for the disease.[5],[6],[7],[8] Subsequently, various researchers classified OSMF both, clinically and histologically – Desa (1957), Pindborg and Sirsat (1966), Agarwal et al. (1971), Pindborg (1989), Katharia et al. (1992), Nagesh and Bailor (1993), Maher et al. (1996), Ranganathan et al. (2001), Rajendran (2003), Kiran Kumar et al. (2007), Tinky Bose and Anita Balan (2007) and Chandramani More (2012).[5],[8]

OSMF is predominantly seen in people of South and Southeast Asia – India, Bangladesh, Sri Lanka, Pakistan, Taiwan, Southern China, etc., where chewing of betel quid, areca nut or its flavored formulations is frequently practiced. The rapid increase in the prevalence of this disease is due to an upsurge in the popularity of commercially available areca nut and tobacco preparations – gutkha, pan masala, flavored areca nut, mawa, etc., in Asian countries [Table 1]. It causes significant morbidity, in terms of loss of mouth function as tissues become rigid and mouth opening becomes difficult, and mortality because of transformation into squamous cell carcinoma.[4],[5],[6],[8],[9],[10],[11],[12]
Table 1: Commercially available arecanut preparations

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The prevalence rate of OSMF in Indian population differs geographically. The male-to-female ratio of OSF was 4.9:1.[8],[10],[11] A considerable difference in the prevalence of OSMF in Europe, UK, USA and Middle East countries has been reported on Asian migrants. Sporadic cases among the non-Asians have also been reported in the literature.[8],[12],[13],[14]

OSMF affects the upper digestive tract – oral cavity, oropharynx and upper third of esophagus and is characterized by Juxta – epithelial inflammatory reaction, followed by fibroelastic changes due to progressive fibrosis of the submucosal tissues (lamina propria and deeper connective tissues) with epithelial atrophy leading to stiffness and rigidity of the oral mucosa and eventual inability to open the mouth.[4],[8],[10],[11],[13],[14]

The etiology of OSMF is obscure, although various hypotheses are proposed, suggesting multifactorial origins, such as chewing of areca nut and its flavored formulations (most common), chronic nutritional deficiencies (especially iron, Vitamin B complex and protein) and genetic predisposition, autoimmunity Excessive use of areca nut and its flavored formulations disrupts the hemostatic equilibrium between synthesis and degeneration.[4],[7],[8],[9],[11],[15],[16] The copper ion in areca nut increases the activity of lysyl oxidase leading to unregulated collagen production, thereby causing oral fibrosis. This leads to the production of free radicals and reactive oxygen species, which are responsible for high rate of oxidation–peroxidation of polyunsaturated fatty acids.[2],[4],[8],[17],[18],[19]

OSMF is a disease of middle age group with peak incidence observed in the second to fourth decade of life. The sex distribution of OSMF varies geographically. The most common oral site for OSMF is buccal mucosa and retromolar region, followed by soft palate, faucial pillars, floor of mouth, tongue, labial mucosa and gingiva[2],[4],[6],[8],[11],[12] [Figure 1].
Figure 1: Oral submucous fibrosis involving various areas of the oral cavity. (a and b) Significant blanching and presence of palpable, thick fibrous bands on the left and right buccal mucosa. Note the brownish-black pigmentation in the posterior vestibular region in b. (c and d) Blanching of the soft palate and faucial pillars. Note the shrunken uvula and its altered shape. (e) Blanching of the floor of mouth and loss of surface texture. (f-i) Blanching and palpable fibrous bands of the upper and lower labial mucosa. Note the stiff labial mucosa and presence of blanching of attached gingiva in f and g

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The clinical presentation will vary according to the stage of the disease, as mentioned in [Table 2].[2],[4],[5],[7],[8],[9],[10],[11],[12],[18],[20] In contrast to other OPMD's, OSMF is insidious in origin and does not regress, either spontaneously or with cessation of habit. The disease remains either stationary or becomes severe, leaving an individual handicapped, both physically and psychologically.[2],[8],[11] Usually, the OSMF lesion shall be biopsied, especially if there are ulcerative, nodular, erythematous and suspicious areas. The histologically proven severe or moderate epithelial dysplasia shall be treated in the lines of management of carcinoma. Nondysplastic or mildly dysplastic cases must be kept under long-term observation and shall be advised antioxidant therapy after discontinuation of habit.[8],[10],[18],[21],[22]
Table 2: Clinical Oro- facial manifestations

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Early diagnosis of OSMF is important in both prevention and therapeutic procedures of oral cancers.[6],[8],[10],[11] The treatment of OSMF in the last few decades is varied and ineffective, but till date, there is no consensus on the most appropriate management of OSMF. Many treatment protocols for OSMF have been proposed by various researchers since its first diagnosis, so as to alleviate the signs and symptoms of the disease and also to stop the disease progression and malignant transformation. In spite of numerous drugs or interventions in practice, the complete remission of OSMF is not achieved and is unsatisfactory. Hence, an attempt of finding a permanent cure is still in progress.


   Treatments in Practice Top


In recent times, several medicinal (allopathic, homeopathic and Ayurvedic), surgical, physiotherapeutic, etc., have been tried, either alone or in combination, in the treatment of OSMF. In advance cases, surgical intervention is the only treatment modality, but relapse is a major problem. Discontinuation of harmful substance such as areca nut, tobacco and alcohol; increased intake of fresh red fruits and green leafy vegetables [Figure 2] and mineral-rich diet has also been advised.[8] The authors have also made an attempt to compile the present treatment which is in practice, and several following studies conducted in different parts of the world.
Figure 2: Various fruits and vegetables having antioxidant properties

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The studies of Borle and Borle,[13] Khanna and Andrade et al.,[14] Maher et al.[15] and Thakur et al.[16] on multivitamins; Borle and Borle[13] and Nallapu et al.[17] on Vitamin A; Kumar et al.,[18] Karemore and Motwani,[19] Selvam and Dayanand,[23] Patil et al.[21] and Samuel and Renukananda[22] on lycopene; Hastak et al.,[20] Das et al.,[24] Agrawal et al.[25] and Yadav et al.[26] on curcumin; Rajendran et al.[27] and Mehrotra et al.[28] on pentoxifylline; Bhadage et al.[29] on isoxsuprine; Gupta and Sharma[30] on chymotrypsin; Borle and Borle,[13] Krishnamoorthy and Khan,[31] James et al.[32] and Shah et al.[33] on hyaluronidase; James et al.[32] on dexamethasone; Katharia et al.[34] and Ali et al.[35] on placental extract; Jirge et al.[36] on levamisole; Haque et al.[37] on interferon gamma; Goel and Ahmed[38] and Gupta et al.[39] on steroids; Khanna and Andrade et al.[14] Shetty et al.[40] and Mulk et al.[41] on spirulina; Alam et al.[42] and Sudarshan et al.[43] on Aloe vera; Cox and Zoellner et al.[44] on physiotherapy exercises; have put forward positive and negative observations in the treatment of OSMF.


   Proposed Treatment Top


Various treatment regimens for OSMF are proposed to alleviate the signs and symptoms of the disease. Even after seven decades of its description as a precancerous condition, no substantial treatment is available because of its multimodal pathogenesis.[12] The principal author with his vast academic and clinical experience in treating various oral lesions, especially OPMD's, has proposed stage-wise treatment protocol or regimen for OSMF so as to assist early intervention of the disease [Table 3]a,[Table 3]b,[Table 3]c,[Table 3]d,[Table 3]e.
Table 3:

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In addition to the above-proposed treatment protocol, each patient of OSMF shall be counseled for discontinuation of habit and must be advised with increase intake of fresh red fruits and green leafy vegetables along with physiotherapy exercises, especially ballooning, blowing of mouth, opening and closing of the mouth, hot water gargling, etc. The frequency of exercise will depend on the severity of the disease.[8],[11],[18],[23]


   Discussion Top


From the last two decades, use of clinical protocol or guidelines have increased and has become a part of routine practice worldwide. The clinical guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. Most of the hospitals have formulated their own standard operating procedures, which may offer concise instructions on diagnostic or screening test, medical or surgical services, etc. These guidelines act as a tool for making care more consistent and efficient and help in reducing the gap between the clinician's knowledge and the available scientific evidence. Various health specialties and companies are involved in conflict to gain rights over specific procedures or treatments as guidelines or protocols.[45],[46]

The clinical protocol helps in providing quality of care to the patients, but its outcome is not clear; maybe because of difference in understanding, the extent of quality by the stakeholders and hence, the effectiveness of protocol remains incomplete. Protocols have the potential to reduce morbidity and mortality and improve quality of life, at least for some conditions, especially when they promote interventions of proved benefit.[47]

Such protocols empower patients to make choices, their personal needs and preferences in selecting the best option. Certainly, sometimes clinicians may first learn about new protocols from patients. The treatment protocols based on a critical appraisal of scientific evidence explain which interventions are of proved benefit. Sometimes, the most important limitation of the protocols is that the recommendations maybe wrong for individual patients.[45],[46],[47],[48]

There is lack of consistent evidence for the effectiveness of any specific interventions for the management of OSMF, and it is difficult to correlate or even combine their outcomes in a scientifically meaningful manner. The literature remains confused because of lack of clarity in scoring system and agreeable treatment outcome measures. Numerous treatments are tried for OSMF, but only few clinical trials are undertaken. Literature has reported variety of clinical outcomes because of failure to standardize the clinical severity scores for OSMF and clarity in distinguishing treatment designs.

Till date, not a single treatment modality has provided a complete relief for this condition, which has high malignant potential. It is difficult to evaluate the advantages and disadvantages of each treatment, especially in combined treatment protocols, because of the empirical nature of each approach. The proposed evidence-based novel clinical protocol for therapeutic intervention is to improve the quality of life in patients suffering from the debilitating condition, OSMF. The present protocol aims to provide the best possible treatment regimen based on sound evidence. The principal author with his vast academic and clinical experience in treating this disease has proposed the stage-wise treatment regimen for OSMF. An attempt is made to compile the available treatment, its current status and future perspectives, so as to assist early intervention of the disease with evidence-based approach.


   Conclusion Top


The evidence for the prevention of any oral disease starts with an understanding of its burden at different stages of life. The time-tested health policies and priority settings direct to have preventive interventions. A variety of treatments are rendered for OSMF till date. The present article has explored all the treatment options available in the existing literature and has suggested the evidence-based treatment protocols for the intervention of OSMF. There is always a scope for further research in the suggested treatment protocol.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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