eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa

Oral Submucous Fibrosis

Author: Nektarios I Lountzis, MD, Staff Physician, Department of Dermatology, Geisinger Medical Center
Coauthor(s): Tammie Ferringer, MD, Teaching Staff, Departments of Dermatology and Pathology, Geisinger Medical Center; Nada MacAron, MD, Staff Physician, Department of Pathology, Emory University School of Medicine; Amy Howard, MD, Fellow, Department of Dermatopathology, Emory University
Contributor Information and Disclosures

Updated: Mar 25, 2009

Introduction

Background

In 1952, Schwartz coined the term atrophica idiopathica mucosa oris to describe an oral fibrosing disease he discovered in 5 Indian women from Kenya.1 Joshi subsequently coined the termed oral submucous fibrosis (OSF) for the condition in 1953.2

Oral submucous fibrosis is a chronic debilitating disease of the oral cavity characterized by inflammation and progressive fibrosis of the submucosal tissues (lamina propria and deeper connective tissues). Oral submucous fibrosis results in marked rigidity and an eventual inability to open the mouth.3,4 The buccal mucosa is the most commonly involved site, but any part of the oral cavity can be involved, even the pharynx.5

The condition is well recognized for its malignant potential and is particularly associated with areca nut chewing, the main component of betel quid. Betel quid chewing is a habit practiced predominately in Southeast Asia and India that dates back for thousands of years. It is similar to tobacco chewing in westernized societies. The mixture of this quid, or chew, is a combination of the areca nut (fruit of the Areca catechu palm tree, erroneously termed betel nut) and betel leaf (from the Piper betel, a pepper shrub), tobacco, slaked lime (calcium hydroxide), and catechu (extract of the Acacia catechu tree).3 Lime acts to keep the active ingredient in its freebase or alkaline form, enabling it to enter the bloodstream via sublingual absorption. Arecoline, an alkaloid found in the areca nut, promotes salivation, stains saliva red, and is a stimulant.

The ingredients and nomenclature of betel quid vary by region as detailed below6,7 :

  • Pan: This is freshly prepared betel quid (with or without tobacco).
  • Gutka (gutkha, guttkha, or guthka): This is a manufactured version of betel quid with tobacco sold as a single-use sachet. It is primarily used on the Indian subcontinent (ie, India, Pakistan, Bangladesh). Betel quid without tobacco is mostly used in Southeast Asian countries (ie, Taiwan, Myanmar, Thailand, China, Papua New Guinea, Guam).
  • Pan masala: This is a commercially manufactured powdered version of betel quid without tobacco used in the Indian subcontinent.
  • Pan Parag: It is a brand name of pan masala and gutka used in India.
  • Mawa (kharra): This is a crude combination of areca, tobacco, and lime.
  • Mainpuri tobacco: Popular in parts of northern India, Mainpuri tobacco is a mixture of areca nut, tobacco, lime, and various condiments. Depending on local preferences, sweeteners or spices (ie, cardamom, saffron, clove, anise seed, turmeric, mustard) are also added as flavorings.

In most patients with oral submucous fibrosis, areca nut was chewed alone more frequently than it was chewed in combination with pan (ie, betel leaf plus lime plus betel catechu, with or without tobacco)4 or had a higher areca nut content.8

Pathophysiology

The pathogenesis of the disease is not well established, but the cause of oral submucous fibrosis is believed to be multifactorial. A number of factors trigger the disease process by causing a juxtaepithelial inflammatory reaction in the oral mucosa. Factors include areca nut chewing, ingestion of chilies, genetic and immunologic processes, nutritional deficiencies, and other factors.

Areca nut (betel nut) chewing

The areca nut component of betel quid plays a major role in the pathogenesis of oral submucous fibrosis.9 In a 2004 study, a clear dose-dependent relationship was observed for both frequency and duration of chewing areca nut (without tobacco) in the development of oral submucous fibrosis.10 Smoking and alcohol consumption alone, habits common to areca nut chewers, have been found to have no effect in the development of oral submucous fibrosis,11 but their addition to areca nut chewing can be a risk for oral submucous fibrosis.11 Commercially freeze-dried products such as pan masala, guthka, and mawa have higher concentrations of areca nut per chew and appear to cause oral submucous fibrosis more rapidly than self-prepared conventional betel quid, which contains smaller amounts of areca nut.8

Arecoline, an active alkaloid found in betel nuts, stimulates fibroblasts to increase production of collagen by 150%.12 In one study, arecoline was found to elevate the mRNA and protein expression of cystatin C, a nonglycosylated basic protein consistently up-regulated in a variety of fibrotic diseases, in a dose-dependent manner in persons with oral submucous fibrosis.13

In 3 separate but similar studies, keratinocyte growth factor-1, insulinlike growth factor-1, and interleukin 6 expression, which have all been implicated in tissue fibrogenesis, were also significantly up-regulated in persons with oral submucous fibrosis due to areca quid chewing, and arecoline may be responsible for their enhanced expression.14,15,16 Further studies have shown that arecoline is an inhibitor of metalloproteinases (particularly metalloproteinase-2) and a stimulator of tissue inhibitor of metalloproteinases, thus decreasing the overall breakdown of tissue collagen.17

Insertion/deletion 5A polymorphism in the promoter region of the matrix metalloproteinase-3 gene, which results in alteration of transcriptional activities, has also been found in persons with oral submucous fibrosis but not in those with oral squamous cell carcinoma.18 Conversely, insertion/deletion 2G polymorphism in the promoter of the matrix metalloproteinase-1 gene has been implicated in oral squamous cell carcinoma but not oral submucous fibrosis.19

Flavanoid, catechin, and tannin in betel nuts cause collagen fibers to cross-link, making them less susceptible to collagenase degradation.20 This results in increased fibrosis by causing both increased collagen production and decreased collagen breakdown.4 Oral submucous fibrosis remains active even after cessation of the chewing habit, suggesting that components of the areca nut initiate oral submucous fibrosis and then affect gene expression in the fibroblasts, which then produce greater amounts of normal collagen.21 Chewing areca quid may also activate NF-kappaB expression, thereby stimulating collagen fibroblasts and leading to further fibrosis in persons with oral submucous fibrosis.22

Areca nuts have also been shown to have a high copper content, and chewing areca nuts for 5-30 minutes significantly increases soluble copper levels in oral fluids. This increased level of soluble copper supports the hypothesis that copper acts as an initiating factor in persons with oral submucous fibrosis by stimulating fibrogenesis through up-regulation of copper-dependent lysyl oxidase activity.23 Further, a significant gradual increase in serum copper levels from precancer to cancer patients has been documented,24 which may have a role in oral fibrosis to cancer pathogenesis.

Ingestion of chilies

The role of chili ingestion in the pathogenesis of oral submucous fibrosis is controversial. The incidence of oral submucous fibrosis is lower in Mexico and South America than in India, despite the higher dietary intake of chilies.25 A hypersensitivity reaction to chilies is believed to contribute to oral submucous fibrosis.4 One study demonstrated that the capsaicin in chilies stimulates widespread palatal fibrosis in rats,26 while another study failed to duplicate these results.27

Genetic and immunologic processes

A genetic component is assumed to be involved in oral submucous fibrosis because of the existence of reported cases in people without a history of betel nut chewing9,28 or chili ingestion.28 Patients with oral submucous fibrosis have been found to have an increased frequency of HLA-A10, HLA-B7, and HLA-DR3.4

An immunologic process is believed to play a role in the pathogenesis of oral submucous fibrosis.29 The increase in CD4 and cells with HLA-DR in oral submucous fibrosis tissues suggests that most lymphocytes are activated and that the number of Langerhans cells is increased. The presence of these immunocompetent cells and the high ratio of CD4 to CD8 in oral submucous fibrosis tissues suggest an ongoing cellular immune response that results in an imbalance of immunoregulation and an alteration in local tissue architecture.30 These reactions may be the result either of direct stimulation from exogenous antigens, such as areca alkaloids, or of changes in tissue antigenicity that lead to an autoimmune response.30

Further, the major histocompatibility complex class I chain–related gene A (MICA) is expressed by keratinocytes and other epithelial cells and interacts with gamma/delta T cells localized in the submucosa. MICA has a triplet repeat (GCT) polymorphism in the transmembrane domain, resulting in 5 distinct allelic patterns. In particular, the phenotype frequency of allele A6 of MICA in subjects with oral submucous fibrosis is significantly higher and suggests a risk for oral submucous fibrosis.31

Some authors have demonstrated increased levels of proinflammatory cytokines and reduced antifibrotic interferon gamma (IFN-gamma) in patients with oral submucous fibrosis, which may be central to the pathogenesis of oral submucous fibrosis.32

Nutritional deficiencies

Iron deficiency anemia, vitamin B complex deficiency, and malnutrition are promoting factors that derange the repair of the inflamed oral mucosa, leading to defective healing and resultant scarring.4 The resulting atrophic oral mucosa is more susceptible to the effects of chilies and betel nuts.

Other significant factors

Some authors have found a high frequency of mutations in the APC gene and low expression of the wild-type TP53 tumor suppressor gene product in patients with oral submucous fibrosis, providing some explanation for the increased risk of oral squamous cell carcinoma development in patients with oral submucous fibrosis.9 Other studies have suggested that altered expression of retinoic acid receptor-beta may be related to the disease pathogenesis.33

Frequency

United States

Oral submucous fibrosis is rare in the United States and is found only in the immigrant members of the South Asian population who chew betel nuts.

International

Worldwide, estimates of oral submucous fibrosis indicate that 2.5 million people are affected, with most cases concentrated on the Indian subcontinent, especially southern India.3 The rate varies from 0.2-2.3% in males and 1.2-4.57% in females in Indian communities.4 Oral submucous fibrosis is widely prevalent in all age groups and across all socioeconomic strata in India. A sharp increase in the incidence of oral submucous fibrosis was noted after pan parag came onto the market, and the incidence continues to increase. Oral submucous fibrosis also occurs in other parts of Asia and the Pacific Islands.3 Migration of endemic betel quid chewers has also made oral submucous fibrosis a public health issue in many parts of the world, including the United Kingdom, South Africa, and many Southeast Asian countries.34

Mortality/Morbidity

Oral submucous fibrosis has a high rate of morbidity because is causes a progressive inability to open the mouth, resulting in difficulty eating and consequent nutritional deficiencies. Oral submucous fibrosis also has a significant mortality rate because of it can transform into oral cancer, particularly squamous cell carcinoma, at a rate of 7.6%.4

Race

Oral submucous fibrosis occurs on the Indian subcontinent, in Indian immigrants to other countries, and among Asians and Pacific Islanders as a result of the traditional use of betel quid endemic to these areas.3

Sex

The male-to-female ratio of oral submucous fibrosis varies by region, but females tend to predominate. In a study from Durban, South Africa, a distinct female predominance was demonstrated, with a male-to-female ratio of 1:13.35 This was later confirmed by others, with a male-to-female ratio of 1:7.36 In addition, a female predominance in areca nut chewing was also noted in this region. Studies in Pakistan reported a male-to-female ratio of 1:2.3.4

Conversely, a case-control study of 185 subjects in Chennai, South India revealed a male-to-female ratio 9.9:1.11 In Patna, Bihar (also in India), the male-to-female ratio was 2.7:1.37 With the onset of new commercial betel quid preparations, trends in sex predominance and age of occurrence may shift.

Age

The age range of patients with oral submucous fibrosis is wide and regional; it is even prevalent among teenagers in India. In a study performed in Saipan, 8.8% of teenagers with a mean age of 16.3 years (± 1.5 y) were found to have oral submucous fibrosis.38 Generally, patient age ranges from 11-60 years4,37 ; most patients are aged 45-54 years and chew betel nuts 5 times per day.4

Clinical

History

Symptoms of oral submucous fibrosis include the following3 :

  • Progressive inability to open the mouth (trismus) due to oral fibrosis and scarring
  • Oral pain and a burning sensation upon consumption of spicy foodstuffs
  • Increased salivation
  • Change of gustatory sensation
  • Hearing loss due to stenosis of the eustachian tubes
  • Dryness of the mouth
  • Nasal tonality to the voice
  • Dysphagia to solids (if the esophagus is involved)
  • Impaired mouth movements (eg, eating, whistling, blowing, sucking)

Physical

Oral submucous fibrosis is clinically divided into 3 stages,39 and the physical findings vary accordingly, as follows3,4,39 :

  • Stage 1: Stomatitis includes erythematous mucosa, vesicles, mucosal ulcers, melanotic mucosal pigmentation, and mucosal petechia.
  • Stage 2: Fibrosis occurs in ruptured vesicles and ulcers when they heal, which is the hallmark of this stage.
    • Early lesions demonstrate blanching of the oral mucosa.
    • Older lesions include vertical and circular palpable fibrous bands in the buccal mucosa and around the mouth opening or lips, resulting in a mottled, marblelike appearance of the mucosa because of the vertical, thick, fibrous bands running in a blanching mucosa. Specific findings include the following:
      • Reduction of the mouth opening (trismus)
      • Stiff and small tongue
      • Blanched and leathery floor of the mouth
      • Fibrotic and depigmented gingiva
      • Rubbery soft palate with decreased mobility
      • Blanched and atrophic tonsils
      • Shrunken budlike uvula
      • Sinking of the cheeks, not commensurate with age or nutritional status
  • Stage 3: Sequelae of oral submucous fibrosis are as follows:
    • Leukoplakia is precancerous and is found in more than 25% of individuals with oral submucous fibrosis.
    • Speech and hearing deficits may occur because of involvement of the tongue and the eustachian tubes.

Causes

The term oral submucosal fibrosis derives from oral (meaning mouth), submucosal (meaning below the mucosa of the mouth), and fibrosis (meaning hardening and scarring).4 Chewable agents, primarily betel nuts (Areca catechu), contain substances that irritate the oral mucosa, making it lose its elasticity. Nutritional deficiencies, ingestion of chilies, and immunologic processes may also have a role in the development of oral submucous fibrosis.3 See Pathophysiology.

More on Oral Submucous Fibrosis

Overview: Oral Submucous Fibrosis
Differential Diagnoses & Workup: Oral Submucous Fibrosis
Treatment & Medication: Oral Submucous Fibrosis
Follow-up: Oral Submucous Fibrosis
References
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References

  1. Schwartz J. Atrophia Idiopathica Mucosae Oris. London: Demonstrated at the 11th Int Dent Congress; 1952.

  2. Joshi SG. Fibrosis of the palate and pillars. Indian J Otolaryngol. 1953;4:1.

  3. Cox SC, Walker DM. Oral submucous fibrosis. A review. Aust Dent J. Oct 1996;41(5):294-9. [Medline].

  4. Aziz SR. Oral submucous fibrosis: an unusual disease. J N J Dent Assoc. Spring 1997;68(2):17-9. [Medline].

  5. Paissat DK. Oral submucous fibrosis. Int J Oral Surg. Oct 1981;10(5):307-12. [Medline].

  6. Centers for Disease Control and Prevention. Fact Sheet. Betel Quid with Tobacco (Gutka). Centers for Disease Control and Prevention. Available at http://www.cdc.gov/tobacco/data_statistics/fact_sheets/smokeless/betel_quid.htm. Accessed February 2007.

  7. Gupta PC. UICC Tobacco Control Fact Sheet No. 17: Areca Nut. International Union Against Cancer. Available at http://www.globalink.org/tobacco/fact_sheets/17fact.htm. Accessed February 1996.

  8. Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol. Jul 2006;42(6):561-8. [Medline].

  9. Liao PH, Lee TL, Yang LC, Yang SH, Chen SL, Chou MY. Adenomatous polyposis coli gene mutation and decreased wild-type p53 protein expression in oral submucous fibrosis: a preliminary investigation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Aug 2001;92(2):202-7. [Medline].

  10. Jacob BJ, Straif K, Thomas G, et al. Betel quid without tobacco as a risk factor for oral precancers. Oral Oncol. Aug 2004;40(7):697-704. [Medline].

  11. Ranganathan K, Devi MU, Joshua E, Kirankumar K, Saraswathi TR. Oral submucous fibrosis: a case-control study in Chennai, South India. J Oral Pathol Med. May 2004;33(5):274-7. [Medline].

  12. Canniff JP, Harvey W. The aetiology of oral submucous fibrosis: the stimulation of collagen synthesis by extracts of areca nut. Int J Oral Surg. 1981;10:163-7. [Medline].

  13. Chung-Hung T, Shun-Fa Y, Yu-Chao C. The upregulation of cystatin C in oral submucous fibrosis. Oral Oncol. Aug 2007;43(7):680-5. [Medline].

  14. Tsai CH, Yang SF, Chen YJ, Chou MY, Chang YC. Raised keratinocyte growth factor-1 expression in oral submucous fibrosis in vivo and upregulated by arecoline in human buccal mucosal fibroblasts in vitro. J Oral Pathol Med. Feb 2005;34(2):100-5. [Medline].

  15. Tsai CH, Yang SF, Chen YJ, Chu SC, Hsieh YS, Chang YC. Regulation of interleukin-6 expression by arecoline in human buccal mucosal fibroblasts is related to intracellular glutathione levels. Oral Dis. Nov 2004;10(6):360-4. [Medline].

  16. Tsai CH, Yang SF, Chen YJ, Chou MY, Chang YC. The upregulation of insulin-like growth factor-1 in oral submucous fibrosis. Oral Oncol. Oct 2005;41(9):940-6. [Medline].

  17. Chang YC, Yang SF, Tai KW, Chou MY, Hsieh YS. Increased tissue inhibitor of metalloproteinase-1 expression and inhibition of gelatinase A activity in buccal mucosal fibroblasts by arecoline as possible mechanisms for oral submucous fibrosis. Oral Oncol. Feb 2002;38(2):195-200. [Medline].

  18. Tu HF, Liu CJ, Chang CS, et al. The functional (-1171 5A-->6A) polymorphisms of matrix metalloproteinase 3 gene as a risk factor for oral submucous fibrosis among male areca users. J Oral Pathol Med. Feb 2006;35(2):99-103. [Medline].

  19. Lin SC, Chung MY, Huang JW, Shieh TM, Liu CJ, Chang KW. Correlation between functional genotypes in the matrix metalloproteinases-1 promoter and risk of oral squamous cell carcinomas. J Oral Pathol Med. Jul 2004;33(6):323-6. [Medline].

  20. Harvey W, Scutt A, Meghji S, Canniff JP. Stimulation of human buccal mucosa fibroblasts in vitro by betel-nut alkaloids. Arch Oral Biol. 1986;31(1):45-9. [Medline].

  21. van Wyk CW, Stander I, Padayachee A, Grobler-Rabie AF. The areca nut chewing habit and oral squamous cell carcinoma in South African Indians. A retrospective study. S Afr Med J. Jun 1993;83(6):425-9. [Medline].

  22. Ni WF, Tsai CH, Yang SF, Chang YC. Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts. Oral Oncol. Jul 2007;43(6):557-62. [Medline].

  23. Trivedy CR, Warnakulasuriya KA, Peters TJ, Senkus R, Hazarey VK, Johnson NW. Raised tissue copper levels in oral submucous fibrosis. J Oral Pathol Med. Jul 2000;29(6):241-8. [Medline].

  24. Khanna SS, Karjodkar FR. Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer : a randomised, controlled clinical trial. Head Face Med. Oct 16 2006;2:33. [Medline].

  25. Pillai R, Balaram P, Reddiar KS. Pathogenesis of oral submucous fibrosis. Relationship to risk factors associated with oral cancer. Cancer. Apr 15 1992;69(8):2011-20. [Medline].

  26. Sirsat SM, Khanolkar VR. Submucous fibrosis of the palate in diet-preconditioned Wistar rats. Induction by local painting of capsaicin--an optical and electron microscopic study. Arch Pathol. Aug 1960;70:171-9. [Medline].

  27. Hamner JE 3rd, Looney PD, Chused TM. Submucous fibrosis. Oral Surg Oral Med Oral Pathol. Mar 1974;37(3):412-21. [Medline].

  28. Seedat HA, van Wyk CW. Submucous fibrosis in non-betel nut chewing subjects. J Biol Buccale. Mar 1988;16(1):3-6. [Medline].

  29. Canniff JP, Harvey W, Harris M. Oral submucous fibrosis: its pathogenesis and management. Br Dent J. Jun 21 1986;160(12):429-34. [Medline].

  30. Haque MF, Harris M, Meghji S, Speight PM. An immunohistochemical study of oral submucous fibrosis. J Oral Pathol Med. Feb 1997;26(2):75-82. [Medline].

  31. Liu CJ, Lee YJ, Chang KW, Shih YN, Liu HF, Dang CW. Polymorphism of the MICA gene and risk for oral submucous fibrosis. J Oral Pathol Med. Jan 2004;33(1):1-6. [Medline].

  32. Haque MF, Meghji S, Khitab U, Harris M. Oral submucous fibrosis patients have altered levels of cytokine production. J Oral Pathol Med. Mar 2000;29(3):123-8. [Medline].

  33. Kaur J, Chakravarti N, Mathur M, Srivastava A, Ralhan R. Alterations in expression of retinoid receptor beta and p53 in oral submucous fibrosis. Oral Dis. Jul 2004;10(4):201-6. [Medline].

  34. Paul RR, Mukherjee A, Dutta PK, et al. A novel wavelet neural network based pathological stage detection technique for an oral precancerous condition. J Clin Pathol. Sep 2005;58(9):932-8. [Medline].

  35. Seedat HA, van Wyk CW. Betel-nut chewing and submucous fibrosis in Durban. S Afr Med J. Dec 3 1988;74(11):568-71. [Medline].

  36. VanWyk CW. Oral submucous fibrosis. The South African experience. Indian J Dent Res. Apr-Jun 1997;8(2):39-45. [Medline].

  37. Ahmad MS, Ali SA, Ali AS, Chaubey KK. Epidemiological and etiological study of oral submucous fibrosis among gutkha chewers of Patna, Bihar, India. J Indian Soc Pedod Prev Dent. Jun 2006;24(2):84-9. [Medline].

  38. Oakley E, Demaine L, Warnakulasuriya S. Areca (betel) nut chewing habit among high-school children in the Commonwealth of the Northern Mariana Islands (Micronesia). Bull World Health Organ. Sep 2005;83(9):656-60. [Medline].

  39. Pindborg JJ. Oral submucous fibrosis: a review. Ann Acad Med Singapore. Sep 1989;18(5):603-7. [Medline].

  40. Ahmed A, Amjad M. Localized morphoea associated with oral submucous fibrosis. J Coll Physicians Surg Pak. Feb 2006;16(2):141-2. [Medline].

  41. Rooban T, Saraswathi TR, Al Zainab FH, Devi U, Eligabeth J, Ranganathan K. A light microscopic study of fibrosis involving muscle in oral submucous fibrosis. Indian J Dent Res. Oct-Dec 2005;16(4):131-4. [Medline].

  42. Ranganathan K, Kavitha R, Sawant SS, Vaidya MM. Cytokeratin expression in oral submucous fibrosis--an immunohistochemical study. J Oral Pathol Med. Jan 2006;35(1):25-32. [Medline].

  43. Pindborg JJ. Oral precancer. In: Barnes L, ed. Surgical Pathology of the Head and Neck. New York, NY: Marcel Dekker; 1995:279-331.

  44. van Wyk CW, Seedat HA, Phillips VM. Collagen in submucous fibrosis: an electron-microscopic study. J Oral Pathol Med. Apr 1990;19(4):182-7. [Medline].

  45. Sur TK, Biswas TK, Ali L, Mukherjee B. Anti-inflammatory and anti-platelet aggregation activity of human placental extract. Acta Pharmacol Sin. Feb 2003;24(2):187-92. [Medline].

  46. Anil S, Beena VT. Oral submucous fibrosis in a 12-year-old girl: case report. Pediatr Dent. Mar-Apr 1993;15(2):120-2. [Medline].

  47. Kakar PK, Puri RK, Venkatachalam VP. Oral submucous fibrosis--treatment with hyalase. J Laryngol Otol. Jan 1985;99(1):57-9. [Medline].

  48. Haque MF, Meghji S, Nazir R, Harris M. Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis. J Oral Pathol Med. Jan 2001;30(1):12-21. [Medline].

  49. 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. Feb 2007;103(2):207-13. [Medline].

  50. Rajendran R, Rani V, Shaikh S. Pentoxifylline therapy: a new adjunct in the treatment of oral submucous fibrosis. Indian J Dent Res. Oct-Dec 2006;17(4):190-8. [Medline].

  51. Hosein M. Oral cancer in Pakistan. The problem and can we reduce it?. In: Oral Oncology. Kluwer Academic: 1994.

  52. Nayak DR, Mahesh SG, Aggarwal D, Pavithran P, Pujary K, Pillai S. Role of KTP-532 laser in management of oral submucous fibrosis. J Laryngol Otol. Oct 10 2008;1-4. [Medline].

  53. Borle RM, Borle SR. Management of oral submucous fibrosis: a conservative approach. J Oral Maxillofac Surg. Aug 1991;49(8):788-91. [Medline].

  54. Gupta SC, Khanna S, Singh M, Singh PA. Histological changes to palatal and paratubal muscles in oral submucous fibrosis. J Laryngol Otol. Dec 2000;114(12):947-50. [Medline].

  55. Eipe N. The chewing of betel quid and oral submucous fibrosis and anesthesia. Anesth Analg. Apr 2005;100(4):1210-3. [Medline].

  56. Murti PR, Bhonsle RB, Pindborg JJ, Daftary DK, Gupta PC, Mehta FS. Malignant transformation rate in oral submucous fibrosis over a 17-year period. Community Dent Oral Epidemiol. Dec 1985;13(6):340-1. [Medline].

  57. Jeng JH, Kuo ML, Hahn LJ, Kuo MY. Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro. J Dent Res. May 1994;73(5):1043-9. [Medline].

  58. Maher R, Lee AJ, Warnakulasuriya KA, Lewis JA, Johnson NW. Role of areca nut in the causation of oral submucous fibrosis: a case-control study in Pakistan. J Oral Pathol Med. Feb 1994;23(2):65-9. [Medline].

  59. International Agency for Research on Cancer. Tobacco habits other than smoking, betel-quid and areca nut chewing, and some related nitrosamines. Lyon, France: International Agency for Research on Cancer; 1984. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans.

  60. Khanna JN, Andrade NN. Oral submucous fibrosis: a new concept in surgical management. Report of 100 cases. Int J Oral Maxillofac Surg. Dec 1995;24(6):433-9. [Medline].

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Further Reading

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Keywords

oral submucous fibrosis, OSF, Asian sideropenic dysphagia, atrophica idiopathica mucosa oris, oral disease, oral cancer, oral fibrosis, oral mucosal disease, oral soft tissue disease, sub-mucous fibrosis, betel nut chewing, Areca catechu, pan parag, gutka, gutkha, guttkha, guthka, betel nut, pan, betel quid, areca nut, mawa, mainpuri

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Contributor Information and Disclosures

Author

Nektarios I Lountzis, MD, Staff Physician, Department of Dermatology, Geisinger Medical Center
Nektarios I Lountzis, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Tammie Ferringer, MD, Teaching Staff, Departments of Dermatology and Pathology, Geisinger Medical Center
Tammie Ferringer, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Society of Dermatopathology
Disclosure: Nothing to disclose.

Nada MacAron, MD, Staff Physician, Department of Pathology, Emory University School of Medicine
Nada MacAron, MD is a member of the following medical societies: College of American Pathologists and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Amy Howard, MD, Fellow, Department of Dermatopathology, Emory University
Disclosure: Nothing to disclose.

Medical Editor

Alexa F Boer Kimball, MD, MPH, Associate Professor of Dermatology, Harvard University School of Medicine; Vice Chair, Department of Dermatology, Massachusetts General Hospital; Director of Clinical Unit for Research Trials in Skin (CURTIS), Department of Dermatology, Massachusetts General Hospital
Alexa F Boer Kimball, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Drore Eisen, MD, DDS, Consulting Staff, Department of Dermatology, Dermatology Research Associates of Cincinnati
Drore Eisen, MD, DDS is a member of the following medical societies: American Academy of Dermatology, American Academy of Oral Medicine, and American Dental Association
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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