Oral submucous fibrosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Oral submucous fibrosis (OSMF) is a chronic, complex potential potent pre-cancerous ( appox 20% may have chances ) condition characterized by juxta-epithelial inflammatory reaction and progressive fibrosis of the submucosal tissues (lamina propria and deeper connective tissues). As the disease progresses, the jaws become rigid to the point that the sufferer is unable to open their mouth.[1][2] The condition is linked to oral cancers and is associated with areca nut chewing, the main component of betel quid. Areca nut or betel quid chewing, a habit similar to tobacco chewing, is practiced predominantly in Southeast Asia and India, dating back thousands of years.


In 1952, J. Schwartz coined the term atrophica idiopathica mucosa oris to describe an oral fibrosing disease he discovered in five Indian women from Kenya.[3] S.G. Joshi subsequently coined the termed oral submucous fibrosis (OSF) for the condition in 1953.[4]


Oral submucous fibrosis is clinically divided into three stages:[5]

  • Stage 1: Stomatitis
  • Stage 2: Fibrosis
    • a- Early lesions, blanching of the oral mucosa
    • b- Older lesions, vertical and circular palpable fibrous bands in and around the mouth or lips, resulting in a mottled, marble-like appearance of the buccal mucosa
  • Stage 3: Sequelae of oral submucous fibrosis

Khanna and Andrade in 1995 developed a group classification system for the surgical management of trismus:[6]

  • Group I: Earliest stage without mouth opening limitations with an interincisal distance of greater than 35 mm.
  • Group II: Patients with an interincisal distance of 26-35 mm.
  • Group III: Moderately advanced cases with an interincisal distance of 15-26 mm. Fibrotic bands are visible at the soft palate, and pterygomandibular raphe and anterior pillars of fauces are present.
  • Group IVA: Trismus is severe, with an interincisal distance of less than 15 mm and extensive fibrosis of all the oral mucosa.
  • Group IVB: Disease is most advanced, with premalignant and malignant changes throughout the mucosa.


"Exposure to arecanut (Arecacatechu) containing products with or without tobacco (ANCP/T) is currently believed to lead to OSF in individuals with genetic immunologic or nutritional predisposition to the disease. "[7]

This hypersensitivity reaction results in a juxta-epithelial inflammation that leads to increased fibroblastic activity and decreased breakdown of fibers. The fibroblasts are phenotypically modified, and the fibers they form are more stable, produce thicker bundles that progressively become less elastic. once the original loosely arranged fibrous tissue is replaced by the ongoing fibrosis , the movability of the oral tissues is reduced, there is loss of flexibilty and reduced opening of the mouth.

These collagen fibers are non degradable and the phagocytic activity is minimized.

According to a recent cross sectional study the time taken for return of salivary pH to baseline levels after chewing arecanut containing mixtures is significantly longer in habitual users with OSF when compared to unaffected users. [7]


In the initial phase of the disease, the mucosa feels leathery with palpable fibrotic bands. In the advanced stage the oral mucosa loses its resiliency and becomes blanched and stiff. The disease is believed to begin in the posterior part of the oral cavity and gradually spread outward.

Other features of the disease include:

  • Xerostomia
  • Recurrent ulceration
  • Pain in the ear or deafness
  • Nasal intonation of voice
  • Restriction of the movement of the soft palate
  • A budlike shrunken uvula
  • Thinning and stiffening of the lips
  • Pigmentation of the oral mucosa
  • Dryness of the mouth and burning sensation
  • Decreased mouth opening and tongue protrusion


Dried products such as paan masala and gutkha have higher concentrations of areca nut and appear to cause the disease. Other causes include:

  • Immunological diseases
  • Extreme climatic conditions
  • Prolonged deficiency to iron and vitamins in the diet

Common sufferers

The incidence of the disease is higher in people from certain parts of the world including South-East Asia, South Africa and the Middle East.[8]


Biopsy screening is mandatory before treatment.

Treatment includes:

  • Abstention from chewing areca nut (also known as betel nut) and tobacco
  • Minimizing consumption of spicy foods, including chiles
  • Maintaining proper oral hygiene
  • Supplementing the diet with foods rich in vitamins A, B complex, and C and iron
  • Forgoing hot fluids like tea, coffee
  • Forgoing alcohol
  • Employing a dental surgeon to round off sharp teeth and extract third molars

Treatment also includes following:

  • The prescription of chewable pellets of hydrocortisone (Efcorlin); one pellet to be chewed every three to four hours for three to four weeks
  • 0.5 ml intralesional injection Hyaluronidase 1500 IU mixed in 1 ml of Lignocaine into each buccal mucosa once a week for 4 weeks or more as per condition
  • 0.5 ml intralesional injection of Hyaluronidase 1500 IU and 0.5 ml of injection Hydrocortisone acetate 25 mg/ml in each buccal mucosa once a week alternatively for 4 weeks or more as per condition[9]
  • Submucosal injections of hydrocortisone 100 mg once or twice daily depending upon the severity of the disease for two to three weeks
  • Submucosal injections of human chorionic gonadotrophins (Placentrax) 2-3 ml per sitting twice or thrice in a week for three to four weeks
  • Surgical treatment is recommended in cases of progressive fibrosis when interincisor distance becomes less than 2 centimetres (0.787401574 in). (Multiple release incisions deep to mucosa, submucosa and fibrotic tissue and suturing the gap or dehiscence so created by mucosal graft obtained from tongue and Z-plasty. In this procedure multiple deep z-shaped incisions are made into fibrotic tissue and then sutured in a straighter fashion.)
  • Pentoxifylline (Trental), a methylxanthine derivative that has vasodilating properties and increases mucosal vascularity, is also recommended as an adjunct therapy in the routine management of oral submucous fibrosis.[10]
  • IFN-gamma is antifibrotic cytokine which alters collagen synthesis and helps in OSF.[11]
  • Colchicine tablets 0.5 mg twice a day[12]
  • Lycopene, 16 mg a day helps in improvement of OSF[13]

The treatment of patients with oral submucous fibrosis depends on the degree of clinical involvement. If the disease is detected at a very early stage, cessation of the habit is sufficient. Most patients with oral submucous fibrosis present with moderate-to-severe disease. Moderate-to-severe oral submucous fibrosis is irreversible. Medical treatment is symptomatic and predominantly aimed at improving mouth movements.

Stem cell therapy for oral submucosal fibrosis

Recently scientists have proven that intralesional injection of autologous bone marrow stem cells is a safe and effective treatment modality in oral sub mucosal fibrosis. It has been shown autologous bone marrow stem cell injections induces angiogenesis in the area of lesion which in turn decreases the extent of fibrosis thereby leading to significant increase in mouth opening.[14][15]

See also


  1. Cox, S. C.; Walker, D. M. (1996). "Oral submucous fibrosis. A review". Australian Dental Journal. 41 (5): 294–9. doi:10.1111/j.1834-7819.1996.tb03136.x. PMID 8961601.
  2. Aziz, SR (1997). "Oral submucous fibrosis: an unusual disease". Journal of the New Jersey Dental Association. 68 (2): 17–9. PMID 9540735.
  3. Hetland, G.; Johnson, E.; Lyberg, T.; Bernardshaw, S.; Tryggestad, A. M. A.; Grinde, B. (2008). "Effects of the Medicinal MushroomAgaricus blazeiMurill on Immunity, Infection and Cancer". Scandinavian Journal of Immunology. 68 (4): 363–70. doi:10.1111/j.1365-3083.2008.02156.x. PMID 18782264.
  4. Joshi, SG (1952). "Fibrosis of the palate and pillars". Indian Journal of Otolaryngology. 4 (1): 1–4.
  5. Pindborg, JJ (1989). "Oral submucous fibrosis: a review". Annals of the Academy of Medicine, Singapore. 18 (5): 603–7. PMID 2694917.
  6. Khanna, J.N.; Andrade, N.N. (1995). "Oral submucous fibrosis: a new concept in surgical management". International Journal of Oral and Maxillofacial Surgery. 24 (6): 433–9. doi:10.1016/S0901-5027(05)80473-4. PMID 8636640.
  7. 7.0 7.1 "Habit-associated salivary pH changes in oral submucous fibrosis-A controlled cross-sectional study Donoghue M, Basandi PS, Adarsh H, Madhushankari G S, Selvamani M, Nayak P - J Oral Maxillofac Pathol". www.jomfp.in. Retrieved 2015-09-23.
  8. Oral Submucous Fibrosis at eMedicine
  9. Kakar, P. K.; Puri, R. K.; Venkatachalam, V. P. (1985). "Oral Submucous Fibrosis—treatment with hyalase". The Journal of Laryngology & Otology. 99 (1): 57–9. doi:10.1017/S0022215100096286. PMID 3968475.
  10. Rajendran, R; Rani, V; Shaikh, S (2006). "Pentoxifylline therapy: a new adjunct in the treatment of oral submucous fibrosis". Indian Journal of Dental Research. 17 (4): 190–8. PMID 17217216.
  11. Haque, M. F.; Meghji, S.; Nazir, R.; Harris, M. (2001). "Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis". Journal of Oral Pathology and Medicine. 30 (1): 12–21. doi:10.1034/j.1600-0714.2001.300103.x. PMID 11140895.
  12. Krishnamoorthy, Bhuvana; Khan, Mubeen (2013). "Management of oral submucous fibrosis by two different drug regimens: A comparative study". Dental Research Journal. 10 (4): 527–32. PMC 3793419. PMID 24130591.
  13. Kumar, Abhinav; Bagewadi, Anjana; Keluskar, Vaishali; Singh, Mohitpal (2007). "Efficacy of lycopene in the management of oral submucous fibrosis". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 103 (2): 207–13. doi:10.1016/j.tripleo.2006.07.011. PMID 17234537.
  14. Sankaranarayanan S, Padmanaban J, Ramachandran CR, Manjunath S, Baskar S, Senthil Kumar R, Senthil Nagarajan R, Murugan P, Srinivasan V, Abraham S (June 2008). Autologous Bone Marrow stem cells for treatment of Oral Sub-Mucous Fibrosis - a case report. Sixth Annual Meeting of International Society for Stem Cell Research (ISSCR). Philadelphia.
  15. Abraham S, Sankaranarayanan S, Padmanaban J, Manimaran K, Srinivasan V, Senthil Nagarajan R, Murugan P, Manjunath S, Senthil Kumar R, Baskar S (June 2008). Autologous Bone Marrow Stem Cells in Oral Submucous Fibrosis – Our experience in three cases with six months follow-up. 8th Annual Meeting of Japanese Society of Regenerative Medicine. 68. Tokyo, Japan. pp. 233–55.

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