Oral submucous fibrosis

Oral submucous fibrosis is a chronic, complex, premalignant (1% transformation risk) condition of the oral cavity, characterized by juxta-epithelial inflammatory reaction and progressive fibrosis of the submucosal tissues (the lamina propria and deeper connective tissues). As the disease progresses, the oral mucosa becomes fibrotic to the point that the person is unable to open the mouth.[1][2] The condition is remotely linked to oral cancers and is associated with areca nut and / or its by-products chewing, majorly practiced in South and South-East Asian countries.[3] The incidence of OSMF has also increased in the western countries due to the changing habits and constant migrating population.[4]

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Oral submucous fibrosis
Other namesOSMF or OSF
SpecialtyOral medicine and Dentistry and Oral Pathology

Definitions

Per Jens J Pindborg and Satyavati Sirsat (1966) (Pathological definition)- ‘An insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx. Although occasionally preceded by and/or associated with vesicle formation, it is always associated with a juxta-epithelial inflammatory reaction followed by a fibro-elastic change of the lamina propria, with epithelial atrophy leading to stiffness.’[5]

Per Chandramani More and Naman Rao (2019) (Clinical definition)- ‘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.’[6]

Epidemiology

The incidence of the disease is higher in people from certain parts of the world including South and South East Asian, South Africa and the Middle Eastern countries.[7]

Symptoms

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 (stomatopyrosis)
  • Decreased mouth opening and tongue protrusion

Causes

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

Pathogenesis

"Exposure to areca nut (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. "[8]

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 flexibility 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 areca nut containing mixtures is significantly longer in habitual users with OSF when compared to unaffected users.[8]

Diagnosis

Classification

Oral submucous fibrosis is clinically divided into three stages:[9]

  • 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:[10]

  • 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.tumor necrosis factor alpha and keratin 17 are

interdependent regulators, they could be used as diagnostic makers and a prognostic mirror of oral submucous fibrosis cases[11]

Treatment

Biopsy screening although necessary is not mandatory most dentist can visually examine the area and proceed with the proper course of 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
  • Interprofessional treatment approach [12]

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[13]
  • 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 (0.79 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.[14]
  • IFN-gamma is antifibrotic cytokine which alters collagen synthesis and helps in OSF.[15]
  • Colchicine tablets 0.5 mg twice a day[16]
  • Lycopene, 16 mg a day helps in improvement of OSF[17]

The treatment of patients with oral submucous fibrosis depends on the degree of clinical involvement. [18] 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. Severe oral submucous fibrosis is irreversible. Moderate oral submucous fibrosis is reversible with cessation of habit and mouth opening exercise. Current modern day medical treatments can make the mouth opening to normal minimum levels of 30 mm mouth opening with proper treatment.

Research

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.[19][20]

History

In 1952, T.Sheikh coined the term distrophica idiopathica mucosa oris to describe an oral fibrosing disease he discovered in five Indian women from Kenya.[21] S.G. Joshi subsequently coined the termed oral submucous fibrosis (OSF) for the condition in 1953.[22]

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See also
  • Cutaneous condition

References
  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. More, CB.; Rao, NR.; More, S.; Johnson, NW. (2020). "Reasons for Initiation of Areca Nut and Related Products in Patients with Oral Submucous Fibrosis within an Endemic Area in Gujarat, India". Substance Use & Misuse. 55 (9): 1413–1421. doi:10.1080/10826084.2019.1660678. PMID 32569538.
  4. Pawar, R.; More, C.; Shah, P.; Rao, N. (2015). "Oral Submucous Fibrosis: An Overview with Evidence Based Management". International Journal of Oral Health Sciences and Advances. 3 (3): 40–9.
  5. Pindborg, J.J.; Sirsat, S.M. (1966). "Oral submucous fibrosis". Oral Surg Oral Med Oral Pathol. 22 (6): 764–79. doi:10.1016/0030-4220(66)90367-7. PMID 5224185.
  6. More, C.; Rao, N. (2019). "Proposed clinical definition for oral submucous fibrosis". Journal of Oral Biology and Craniofacial Research. 9 (4): 311–14. doi:10.1016/j.jobcr.2019.06.016. PMC 6614531. PMID 31334003.
  7. Oral Submucous Fibrosis at eMedicine
  8. Donoghue, M.; Basandi, P. S.; Adarsh, H.; Madhushankari, G. S.; Selvamani, M.; Nayak, P. (2015). "Habit-associated salivary pH changes in oral submucous fibrosis-A controlled cross-sectional study". Journal of Oral and Maxillofacial Pathology. 19 (2): 175–81. doi:10.4103/0973-029X.164529. PMC 4611925. PMID 26604493.
  9. Pindborg, JJ (1989). "Oral submucous fibrosis: a review". Annals of the Academy of Medicine, Singapore. 18 (5): 603–7. PMID 2694917.
  10. 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.
  11. Ghada A. Abd El Latif, Tumor necrosis factor alpha and keratin 17 expression in oral submucous fibrosis in rat model, E.D.J. Vol. 65, (1) Pp 277-288; 2019. DOI: 10.21608/edj.2015.71414
  12. Rao, N.R.; Villa, A.; More, C.B.; Jayasinghe, R.; Kerr, A.R.; Johnson, N.W. (2020). "Oral submucous fibrosis: a contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management". ournal of Otolaryngology-Head & Neck Surgery. 49 (3): 1–11. doi:10.1186/s40463-020-0399-7. PMC 6951010. PMID 31915073.
  13. 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.
  14. 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. doi:10.4103/0970-9290.29865. PMID 17217216.
  15. 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.
  16. 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.
  17. 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.
  18. More, C.; Gavli, N.; Chen, Y.; Rao, N. (2018). "A novel clinical protocol for therapeutic intervention in oral submucous fibrosis: An evidence based approach". Journal of Oral and Maxillofacial Pathology. 22 (3): 382–91. doi:10.4103/jomfp.JOMFP_223_18 (inactive 2020-01-06). PMC 6306594. PMID 30651684.
  19. 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.
  20. 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.
  21. 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.
  22. Joshi, SG (1952). "Fibrosis of the palate and pillars". Indian Journal of Otolaryngology. 4 (1): 1–4.
Classification
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