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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 30  |  Issue : 4  |  Page : 407-411

Oral submucous fibrosis: Current concepts on aetiology and management – A review


1 Department of Oral Medicine and Radiology, Sardar Patel Post Graduate Institute of Dental and Medical Sciences, Lucknow, U.P, India
2 Department of Oral Medicine and Radiology, BBD College of Dental Sciences, Lucknow, U.P, India

Date of Submission19-May-2018
Date of Acceptance22-Oct-2018
Date of Web Publication17-Jan-2019

Correspondence Address:
Dr. Sadiya Khan
Department of Oral Medicine and Radiology, Sardar Patel Post Graduate Institute of Dental And Medical Sciences, Lucknow, U.P
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaomr.jiaomr_89_18

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   Abstract 


Oral submucous fibrosis (OSF) is the chronic debilitating and crippling condition of oral mucosa. It is well recognised as potentially malignant disorder which is associated mainly with the use of arecanut in various forms. It is characterised by inflammation and progressive fibrosis of the submucosal tissue. The pathogenesis of the disease includes various factors like arecanut chewing, chillies, nutritional deficiencies and genetic processes. The management of OSF has been the subject of controversy ever since Schwartz first described the condition in 1952. Through this article, an attempt is made to update the knowledge regarding aetiology and its therapeutic and surgical management which improves the life expectancy of patients suffering from OSF.

Keywords: Aetiology and management, arecanut, oral submucous fibrosis


How to cite this article:
Khan S, Sinha A, Kumar S, Iqbal H. Oral submucous fibrosis: Current concepts on aetiology and management – A review. J Indian Acad Oral Med Radiol 2018;30:407-11

How to cite this URL:
Khan S, Sinha A, Kumar S, Iqbal H. Oral submucous fibrosis: Current concepts on aetiology and management – A review. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2019 Jun 25];30:407-11. Available from: http://www.jiaomr.in/text.asp?2018/30/4/407/250260




   Introduction Top


Oral submucous fibrosis (OSMF) is a chronic insidious disease affecting any part of the oral cavity and sometimes the pharynx. Although, occasionally preceded by or associated with vesical formation, it is always associated with a juxta-epithelial inflammatory reaction followed by fibroelastic changes of lamina propria with epithelial atrophy, leading to stiffness of oral mucosa and causingtrismus and inability to eat.[1]

OSF was first reported in India in 1953 by Joshi and he coined the term submucous fibrosis of palate and faucialpillars.[2] Various other names suggested were diffuse oral submucous fibrosis (Lal, 1953), idiopathic scleroderma of the mouth (Su,1954), idiopathic palatal fibrosis (Rao, 1962) and sclerosing stomatitis (Behl, 1962).[2]

OSF is a disease commonly occurring in the South East Asians and Indian population.[3] Indian population has the highest rate of incidence from the past to the present. Reports from the North Western India give an incidence of 2.6 and 8.5 per 100,000 per year for males and females, respectively; figures in south of India were higher 9 and 20 per 100,000 per year for males and females, respectively.[4],[5]

In 2002,[6] the prevalence was estimated to be 5 million people alone in India and more recent data suggest prevalence of OSF in India has increased from 0.03 to 6.42%.[7]

Male predominance was reported by various authors Sinor et al.[8] and Kumar et al.[9] Wide variation in ages were reported by various authors, Pindborg et al.[5] gave anaveragerange for male 53.6 years and females 37.7 years, Babu et al.[10] and Trivedy et al.[11] reported 23% of patients age ranged between 14 and 19 years. Other authors reported incidence of OSF in younger populations ranging from 20 to 30 years.[12]


   Aetiology Top


Various studies suggested that arecanut is the main aetiological factor for OSF and the only risk for OSF among people who probably have a genetic predisposition to the disease. Other aetiological factors suggested are lime, tobacco, chillies, immunological disorders nutritional deficiencies and collagen disorders.

Acrecanut

The husked whole fruit of arecanut tree and betel is the inner kernel or seed obtained after removing husk. The active alkaloid found in betel nuts is arecoline, which stimulates fibroblast to increase production of collagenat a higher rate than normal.

Also a high amount of copper content is found in arecanut which on chewing it for 5–30 min increasessoluble copper levels in oral fluids, which is an initiating factor in OSF.[13]

Immune system

In OSF cases, the transforming growth factor-beta (TGF-β) and interferon-gamma (IFN-γ) levels are low and the results are correlated with use of betel quid.

Other diseases like rheumatoid arthritis, systemic lupus erythematosus (SLE) and scleroderma are associated with unique human leukocyte antigen (HLA) – DR antigens and similar association is found for OSF.[14]

Nutritional deficiencies

OSF cases have been suspected with subclinical vitamin B complex deficiency.[15] Iron deficiency anaemia, vitamin B complex deficiency and malnutrition are promoting factor that derange the repair of inflamed oral mucosa leading to scarring and defectivehealing.[16]

Chillies also play an aetiological role in OSF[17],[18] as its activeingredient Capsaicin (vanillylamide of 8-methyl-6-nonenic acid) acts as a predisposing factor for fibrosis (Rajendran, 1994).

Tobacco and Lime

Freezed dried forms of mawa, gutkha and pan masala are commercially available with high concentration of arecanut per chew. They cause more irritation to the oral mucosa than self-prepared betel quid.[19]

Malignant transformation and pre-cancerous nature of oral submucous fibrosis

Paymaster in 1956 found the pre-cancerous nature of OSMF when he observed squamous cell carcinoma in one-third of the OSF cases.[20] A malignant transformation rate of 4.5% in 66 cases of OSMF during a period of 4–15 years was observed by Pindborg etal. The malignanttransformation rate in Taiwan was estimated as 3.27–8.63%,[21] whereas in a study by Patil and Maheshwari (2014) reported malignancy in 4.6% OSMF cases.[22]

Classification system

Recent classification systems:

Kerr et al.[23] gave the following grading system for OSMF as:

Grade 1: Mild: Any features of the disease triad for OSMF (burning, depapillation, blanching or leathery mucosa) may be reported and inter-incisal opening >35 mm

Grade 2: Moderate: Above features of OSMF and inter-incisal limitation of opening between 20–35 mm

Grade 3: Severe: Above features of OSF and inter-incisal opening <20 mm

Grade 4A: Above features of OSMF with other potentially malignant disorders on clinical examination

Grade 4B: Above features of OSMF with any grade of oral epithelial dysplasia on biopsy

Grade 5: Above features of OSMF with oral squamous cell carcinoma.

More et al.[24] gave the following classification based on clinical and functional parameters as: I: Clinical staging: Stage 1 (S1): Stomatitis and/or blanching of oral mucosa.

Stage 2 (S2): Presence of palpable fibrous bands in buccal mucosa and/or oropharynx, with/without stomatitis.

Stage 3 (S3): Presence of palpable fibrous bands in buccal mucosa and/or oropharynx, and in any other parts of oral cavity, with/without stomatitis.

Stage 4 (S4): A: Any one of the above stage along with other potentially malignant disorders, e.g., oral leukoplakiaand oral erythroplakia. B: Any one of the above stage along with oral carcinoma.

II: Functional staging:

M1: Inter-incisal mouth opening up to or >35 mm

M2: Inter-incisal mouth opening between 25 to 35 mm

M3: Inter-incisal mouth opening between 15 to 25 mm

M4: Inter-incisal mouth opening <15 mm.

Prakash et al.[25] assessed the morphologic variants of soft palate by conducting a clinic-radiological study. The authors based on these variants assessed the severity of OSMF to establish it as a basis for staging of OSMF. Six morphologic variants were delineated as follows:

Type 1: Leaf shaped

Type 2: Rat tail shaped

Type 3: Butt shaped

Type 4: Straight line

Type 5: Deformed S

Type 6: Crook shaped.

Patil and Maheshwari[22] suggested a new classification based on cheek flexibility. Here, cheek flexibility was measured as a distance in millimetres from maxillary incisal midline to the cheek retractor during retraction. Normal cheek flexibility observed was: males 35–45 mmand females 30–40 mm.

Grade 1 (Early): Cheek flexibility of 30 mm and above

Grade 2 (Mild): Cheek flexibility between 20 to 30 mm

Grade 3 (Moderate): Cheek flexibility less than 20 mm

Grade4 (Severe): Any of the above condition without concurrent presence of potential malignant lesions

Grade 5 (Advanced): Any of the above condition with concurrent presence of oral carcinoma.

Management

OSMF is well known for its resistant and chronic nature. Being a premalignant condition with debilitating consequences, no conservative treatment that has given complete resolution of symptoms is identified till date. Various treatment modalities are available to treat this condition which includes medicinal approach, surgical management andphysiotherapy. Proper treatment begins with education of the patient regarding the ill effects of arecanut and related chewing products. The patient should be informed about the irreversible nature of the disease despite quitting the habit and possibilities of developing oral cancer.

Medical management

Includes

  • Antioxidants
  • Micronutrients
  • Intralesionalinjections
  • Corticosteroids
  • Hyaluronidase
  • Placental extracts
  • IFN-γ.



   Physiotherapy Top


Surgical treatment

Medical management

OSMF is associated with impaired nutritional status, therefore, various investigators have supplemented the patients with multiple micronutrients which includes zinc, vitamin A, B, C, iron, folic acid, copper, calcium and manganese.

Ina study by Kumar et al., 82 OSMF patients were treated for 12 weeks. They were divided intofive groups. Group A were given 50,000IU of vitamin A, Group B – vitamin A 50,000IU with zinc sulphate 220 mg TDS, Group C – zinc sulphate 220 mg TDS, Group D – zinc sulphate 220 mg TDS with intralesional hydrocortisone 4 mg/week and Group E – intralesional hydrocortisone 4 mg/week. It was observed that oral zinc either alone or in combination with vitamin A or corticosteroids were found beneficial in the treatment of OSMF.[26]

In a study by Gupta et al. who treated six cases of OSMF with appropriation containing vitamin A palmitate 2500 IU, vitamin E acetate, beta carotene 50mg, vitamin C, zinc, copper and manganese. There was improvement in the symptoms of all the patients.[13]

Lycopene is a major carotenoid which is found in tomato have antioxidant and chemopreventive properties against potentially malignant disorders. Selvam and Dyanand suggested a combination of lycopene with intralesionalsteroids and hyaluronidase to be highly efficacious in reducing the symptoms and mouth opening of OSMF patients.[27] Other authors Karemore and Motwani and Sunderraj S et al. also found that lycopene was highly efficacious in relieving sign and symptoms of OSMF.[28],[29]

Rao found in there study that the use of alpha lipoic acid along with intralesional steroid injections have beneficial impact.[30]

Several glucocorticoids are used for the treatment of OSMF, short acting (hydrocortisone), intermediate acting (triamcinolone) and long acting (betamethasone and dexamethasone). They act by inhibiting inflammatory factor and increasing apoptosis of inflammatory cell, thereby partially relieving symptoms of early stage OSMF. A combination of chymotrypsin (5000 IU), hyaluronidase (1500 IU) and dexamethasone (4 mg) twice weekly submucosal injection for 10 weeks. Current concept is based on the use of intralesionals injected into fibrotic band biweekly for 6 to 8 weeks along with mouth-opening exercises.[31] Placentrex is basically aqueous extract of human placenta which contains enzymes, vitamins, aminoacids, nucleotides and steroids. Placentrexcauses biogenic stimulation and increases vascularity of tissues based on principal of tissue therapy which was introduced by Filatov in 1933. It has been found by various authors that placenta extract significantly improves mouth opening, burning sensation, colour of mucosa and reduction in fibrotic bands.

IFN-γ is proposed to reduce fibroblast proliferation and collagen synthesis and upregulate collagenase synthesis and antifibrotic cytokines. Previously injection when given intralesionally have showed clinical improvement in the cases of hypertrophic scars and keloids. When intralesional IFN-γ was tried in OSMF patients it showed increased mouth opening, suppleness of the mucosa and reduction in burning sensation.[32]

Pentoxifylline is methylxanthine derivative that has vasodilating properties and increases mucosal vascularity. It acts by supressing leukocyte function, altering fibroblast physiology and stimulating fibronylysis. Pentoxifylline 400 mg three times daily for 7 months was used as an adjunct therapy for OSMF. Levamisole 50 mg TDS for three alternate weeks alone have sure significant improvement in mouth opening and burning sensation.[33]

Colchicine inhibits collagen synthesis and increases collagenolytic activity and has found to be of use in OSMF. In a study by Krishnamoorthy et al. reported that 0.5 mg colchicine orally, twice daily along with intralesional 0.5 ml hyaluronidase 1500 IU gives significant improvement in burning sensation and mouth opening.[34]

Curcuma longa is commonly known as haldi, turmeric or Indian saffron belonging to the family Zingiberaceae. It is well known for its anti-inflammatory and antioxidant action.[35] Das in a study found curcumin and turmeric oil as significantly beneficial non-invasive herbal therapy for OSMF.[33],[36] Ramsevak et al. described in his study the anti-inflammatory, cytotoxic and antioxidant activity of curcumin I, II, III from Curcuma longa.[37] Talsanil JR et al. used laser with follow-up physiotherapy to reducedtrismus in OSMF and concluded that diodelaser is an inexpensive and an alternative method which requires less hospital stay and follow-up compared to other surgical methods.[38] Mucoadhesive systems for oral drug delivery are found efficient, targeted drug approach and reduced sideeffects. Curcumin gel having anti-tumeric and anti-mutagenic activity is recommended for extended periods of time in treatment of OSMF. Amlexanox, a potent anti-inflammatory gel, is also preferred for early symptoms of OSMF.

Tea pigments are oxidised products of polyphenols that are derived from tea leaves found to improve haemorheology and microcirculation. Li and Tang found that tea pigments when administered in OSMF act by decreasing high blood viscosity, improving microcirculation and activity of superoxide dismutase.[39]

Aloe vera acts as a wound-healing hormone and serols in aloe vera have strong anti-inflammatory properties. Sudarshan et al. reported use of aloe vera topically in mild stage OSMF and has found improvement in burning sensation and mouth opening as compared to antioxidant therapy.[37]

Spirulina, a microalgae which contains beta carotene, tocopherols and phenolic acid has antioxidant properties. Shetty et al. in a study used 500 mg spirulina twice daily as an adjuvant therapy in early management of OSMF.[40]

Surgical modalities for the treatment of OSMF are chosen according to the clinical stage of OSMF. Surgical excision of fibrotic tissue and covering the defect with fresh human amnion, buccal pad fat grafts. Bande et al. did the comparison of extended nasolabial flap with the platysmamyocutaneous muscle. Flap for reconstruction of intraoral defect after release of OSMF and revelled that both the procedure are equally effective in management, but extraoral scar was not aesthetically acceptable in the nasolabial group.[41]

Oral stent can also be used as an adjunct to prevent surgical relapse.[42] Khanna and Andrade treated advanced cases of OSMF by a new surgical technique of palatal island flap.[43] The latest use of lasers in the surgical management of OSMF is found efficacious. Talsanil et al. used laser with follow-up physiotherapy to reducetrismus in OSMF and concluded that diodelaser is an inexpensive and an alternative method which requires less hospital stay and follow-up compared to other surgical methods.[38]


   Conclusion Top


OSMF is mainly a disease of Indian sub-continent where arecanut chewing is rampant. Thus there is anurgent need to initiate public health education measures to educate people about the debilitating, oral premalignant condition before it istoo late. Till date, no definitive and widely excepted treatment is currently available. Being a chronic debilitating disease there is a need of herbal medication to be used for longer periods as they have lesser side effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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