Oral Submucous Fibrosis: Treatment & Medication

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

• Print This

• Email This

• Overview
• Differential Diagnoses & Workup
• Treatment & Medication
• Follow-up
• References
• Keywords

Treatment

Medical Care
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. Treatment
strategies include the following4 :

• Steroids: In patients with moderate oral submucous fibrosis, weekly submucosal intralesional injections
or topical application of steroids may help prevent further damage.
• Placental extracts: The rationale for using placental extract in patients with oral submucous fibrosis
derives from its proposed anti-inflammatory effect,45 hence, preventing or inhibiting mucosal damage.
Cessation of areca nut chewing and submucosal administration of aqueous extract of healthy human
placental extract (Placentrex) has shown marked improvement of the condition.46
• Hyaluronidase: The use of topical hyaluronidase has been shown to improve symptoms more quickly
than steroids alone. Hyaluronidase can also be added to intralesional steroid preparations. The
combination of steroids and topical hyaluronidase shows better long-term results than either agent
used alone.47
• IFN-gamma: This plays a role in the treatment of patients with oral submucous fibrosis because of its
immunoregulatory effect. IFN-gamma is a known antifibrotic cytokine. IFN-gamma, through its effect of
altering collagen synthesis, appears to be a key factor to the treatment of patients with oral submucous
fibrosis, and intralesional injections of the cytokine may have a significant therapeutic effect on oral
submucous fibrosis.48
• Lycopene: Newer studies highlight the benefit of this oral nutritional supplement at a daily dose of 16
mg. Mouth opening in 2 treatment arms (40 patients total) was statistically improved in patients with
oral submucous fibrosis. This effect was slightly enhanced with the injection of intralesional
 betamethasone (two 1-mL ampules of 4 mg each) twice weekly, but the onset of effect was slightly
delayed.49
• Pentoxifylline: In a pilot study, 14 test subjects with advanced oral submucous fibrosis given
pentoxifylline at 400 mg 3 times daily were compared to 15 age- and sex-matched diseased control
subjects. Statistical improvement was noted in all measures of objective (mouth opening, tongue
protrusion, and relief from fibrotic bands) and subjective (intolerance to spices, burning sensation of
mouth, tinnitus, difficulty in swallowing, and difficulty in speech) symptoms over a 7-month period.50
Further studies are needed, but this could be used in conjunction with other therapies.
The role of these treatments is still evolving. The US Food and Drug Administration has not yet approved these
drugs for the treatment of oral submucous fibrosis.

Surgical Care
Surgical treatment is indicated in patients with severe trismus and/or biopsy results revealing dysplastic or
neoplastic changes. Surgical modalities that have been used include the following:

• Simple excision of the fibrous bands: Excision can result in contracture of the tissue and exacerbation
of the condition.
• Split-thickness skin grafting following bilateral temporalis myotomy or coronoidectomy: Trismus
associated with oral submucous fibrosis may be due to changes in the temporalis tendon secondary to
oral submucous fibrosis; therefore, skin grafts may relieve symptoms.29
• Nasolabial flaps and lingual pedicle flaps: Surgery to create flaps is performed only in patients with oral
submucous fibrosis in whom the tongue is not involved.51
• Use of a KTP-532 laser release procedure was found to increase mouth opening range in 9 patients
over a 12-month follow-up period in one study.52
Consultations
• Consult an ear, nose, and throat specialist for evaluation of dysplasia and close follow-up monitoring
for the development of oral cancer.
• Consult a plastic surgeon for patients with severe trismus, in whom reconstructive surgery may be
possible.
Diet
• Dietary focus should be on reducing exposure to the risk factors, especially the use of betel quid, and
correcting any nutritional deficiencies, such as iron and vitamin B complex deficiencies.3
Activity
• Physical therapy using muscle-stretching exercises for the mouth may be helpful in preventing further
limitation of mouth movements. This is often combined with medical and surgical therapy.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. In addition to the
medications listed below, placental extract has been used experimentally at a dose of 50 mcg/m2 SC 3 times
per week if the patient's body surface area (BSA) is greater than 0.52 m2 or 1.5 mcg/kg/dose SC 3 times per
week if the BSA is less than or equal to 0.5 m2.

Corticosteroids
 Can be used in pharmacologic doses for their anti-inflammatory and immunosuppressant properties and their
effects on blood and lymphatic systems in the palliative treatment of various diseases.

Dexamethasone (Decadron)

For various inflammatory diseases. Decreases inflammation by suppressing migration of polymorphonuclear

leukocytes and reducing capillary permeability.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

4 mg IV/IM (suggested in studies)

Pediatric

Base dose on severity of disease and response rather than age, body weight, or BSA

• Dosing
• Interactions
• Contraindications
• Precautions

Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; decreases effect of salicylates
and vaccines used for immunization

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; active bacterial or fungal infection

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

Precautions

Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when
tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema,
osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia
gravis, growth suppression, and infections are possible complications; caution with individuals exposed to viral
illnesses, such as chickenpox or measles
 Triamcinolone acetonide (Aristocort, Kenaject)

Suppresses immune system by reducing activity and volume of lymphatic system. Treats inflammatory mucosal
lesions that are responsive to steroids. Decreases inflammation by suppressing the migration of
polymorphonuclear leukocytes and by reversing capillary permeability.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

Dental paste (for oral inflammatory or ulcerative lesions): Apply thin film bid/tid pc and hs
IM: 40-80 mg (studies have used 10 mg/mL diluted in 1 mL of lidocaine 2% to avoid tissue irritation and
facilitate proper distribution of drug)

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Coadministration with barbiturates, phenytoin, and rifampin decreases effects; effects of vaccine and toxoid
may be reduced

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; fungal, viral, and mycobacterial mucosal infections

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

Precautions

Multiple complications (eg, severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer
disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression) may occur;
abrupt discontinuation may cause adrenal crisis

Betamethasone valerate (Diprosone)

 For inflammatory reactions responsive to steroids. Decreases inflammation by suppressing migration of
polymorphonuclear leukocytes and by reversing capillary permeability. Affects production of lymphokines and
has inhibitory effect on Langerhans cells.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

Suggested dose: 0.05% topically q6h for 3 wk

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

None reported

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; paronychia; cellulitis; impetigo; angular cheilitis; erythrasma; erysipelas; rosacea;
perioral dermatitis; acne

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

Precautions

Do not use on skin with decreased circulation; can cause atrophy of groin, face, and axillae; may cause striae
distensae and rosacealike eruption; may increase skin fragility; rarely may suppress HPA axis; if infection
develops and is not responsive to antibiotic treatment, discontinue until infection is under control; do not use
monotherapy to treat widespread plaque psoriasis

Extravasation antidotes
Can enhance diffusion of locally irritating or toxic drugs in the management of intravenous extravasation.

Hyaluronidase (Wydase Injection)

 Stimulates hydrolysis of hyaluronic acid, one of the chief ingredients of tissue cement, which offers resistance
to diffusion of liquids through tissues. Used to aid in absorption and dispersion of injected drugs.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

150 U added to vehicle solution and administered SC/ID

Pediatric

Administer as in adults

• Dosing
• Interactions
• Contraindications
• Precautions

Salicylates, cortisone, corticotropin, estrogens, and antihistamines may decrease effects

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

Precautions

Avoid injecting into inflamed or cancerous areas; perform intradermal skin test for sensitivity before initiating
infusion; discontinue if sensitivity or extravasation occur

Interferons
Naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha-, beta-, and
gamma-interferons may be given topically, systemically, or intralesionally.

Interferon gamma (Actimmune)

Believed to act via ability to counteract cell surface expression of proinflammatory or proadhesion molecules on
immune cells, among other effects. More studies needed to fully understand mechanisms of action.
• Dosing
• Interactions
• Contraindications
• Precautions
Adult

BSA >0.5 m2: 50 mcg/m2 SC 3 times/wk

BSA <0.5 m2: 1.5 mcg/kg/dose SC 3 times/wk

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Live vaccines; rotavirus vaccine

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; E coli derivatives or components

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

Precautions

Caution in preexisting cardiac disease, seizure disorder, or compromised CNS function; myelosuppression

Antioxidant
Has been found to possess antioxidant and antiproliferative properties in animal and laboratory studies,
although activity in humans remains controversial. Adult dose below suggested from 1 study.49

Lycopene (LycoRed)

Considered an antioxidant and has antiproliferative properties in animal and laboratory studies, although
activity in humans remains controversial.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

16 mg/d PO (suggested in study)

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions
• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity to lycopene or tomatoes

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Safety of lycopene derivatives has not been rigorously studied but review of available scientific literature finds
tomatoes, tomato-based products, and lycopene supplements generally well tolerated; rare reports of diarrhea,
nausea, stomach pain or cramps, gas, vomiting, and loss of appetite; acidity of tomatoes and tomato-based
products may exacerbate stomach ulcers; although causality is unclear, has been associated with death from a
cancer-related hemorrhage; see MayoClinic.com-Lycopene for more information

Vasodilator
Methylxanthine derivative that has vasodilating properties and may increase mucosal vascularity. Adult dosage
suggested by Rajendran et al.50

Pentoxifylline (Trental)

Methylxanthine derivative that has vasodilating properties and may increase mucosal vascularity.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

400 mg tid as coated, sustained-release tab

 Pediatric

No known indicated pediatric dosage in relation to oral submucous fibrosis

• Dosing
• Interactions
• Contraindications
• Precautions

NSAIDs (or combination formulations with NSAIDs), theophyllines and warfarin

• Dosing
• Interactions
• Contraindications
• Precautions

Avoid in patients with hypersensitivity to medication, class or component, in those with methylxanthine
intolerance, recent cerebral bleed, or recent retinal hemorrhage

• Dosing
• Interactions
• Contraindications
• Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus

Precautions

Baseline creatinine value recommended

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

« Previous Page Next Page »

• Print This

• Email This
[ CLOSE WINDOW ]
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].
[ CLOSE WINDOW ]
Further Reading
[ CLOSE WINDOW ]
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
[ CLOSE WINDOW ]
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.

Top of Form
medscapecme

Bottom of Form
• Search for CME/CE on This Topic »

RELATED EMEDICINE ARTICLES

• Premalignant Conditions of the Oral Cavity (Otolaryngology and Facial Plastic Surgery)
Patient Education
• Cancer and Tumors Center
• Mouth and Throat Cancer Symptoms
• Cancer of the Mouth and Throat Overview
• Mouth and Throat Cancer Causes
• Mouth and Throat Cancer Treatment
Top of Form
 Medscape MedscapeCME eMedicine Drug Reference MEDLINE All

Bottom of Form
• About Emedicine

• Privacy Policy

• Terms of Use

• Help

• Contact Us

• Institutional Subscribers

• Contributor Login

We subscribe to the
HONcode principles of the
Health On the Net Foundation
All material on this website is protected by copyright, Copyright© 1994- 2010 by Medscape.
This website also contains material copyrighted by 3rd parties.
DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified
physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of
an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and
informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you
suspect you are ill.

Close