ORAL SUBMUCOUS FIBROSIS

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ORAL SUBMUCOUS FIBROSIS : 

ORAL SUBMUCOUS FIBROSIS

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Synonyms:- Atrophia Idiopathica tropica mucosae orali - Idiopathic scleroderma of the mouth - Idiopathic palatal fibrosis - Sclerosing stomatitis - Juxta-Epithelial fibrosis (Juxta means near)

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OSMF → Chronic disease of the oral mucosa characterized by inflammation and progressive fibrosis of lamina propria and deeper connective tissues

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A condition with a high risk of malignant transformation Insidious chronic precancerous condition affecting any part of oral cavity & sometimes the pharynx.

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It is preceded by and/or associated with vesicle formation and is always associated with juxta epithelial inflammatory reaction followed by progressive hyalinization of lamina propria

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Later → Subepithelial and submucosal myofibrosis leads to stiffness of oral mucosa and deeper C/T with progressive limitation in opening of the mouth and protrusion of tongue leading to difficult in eating, swallowing and phonation

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Subepithelial and Stiffness of oral submucosal myofibrosis mucosa and deeper C/T(+) ↑ vesicle + Juxta-epithelial inflammation Limitation of mouth opening

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Areca products contain high level of copper (mean 302 nml/g) (Daily intake → 0.6-1.6 mg) Copper intake → ↑ Lysyl oxidase activity → Fibrotic disorder OSMF Hepatic &pulmonary fibrosis Scleroderma Areca nut chewing → Copper > 5mg/ day.

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Areca nut chewing Arecoline, an active alkaloid found in betel nuts, simulates fibroblasts to increase production of collagen

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Flavanoid, catechin, and tannin in betel nuts cause collagen fibers less susceptible to collagenase degradation resulting in increased fibrosis by causing both increased collagen production and decreased collagen breakdown

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Areca nuts shown to have high copper content (chewing areca nuts for 5-30 minutes significantly increases soluble copper levels in oral fluid; copper acts as an initiating factor in patients with OSMF by stimulating fibrogenesis through up-regulation of copper- dependent lysyl oxidase activity

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Ingestion of chilies ( capsaicin, active ingredient of chilies, stimulates widespread palatal fibrosis in rats)

PATHOGENESIS OF OSMF : 

PATHOGENESIS OF OSMF IRON AND OTHER NUTRITIONAL CHRONIC CANDIDIASIS TOBACCO, LIME & BETAL QUID IMMUNE GENETIC ABNORMALITIES SYSTEM CHANGES HSV/HPV AUTOIMMUNITY Normal oral mucosa OSMF

AETIOLOGY : 

AETIOLOGY (1) Tobacco, lime and quid Tobacco smoke → Polycyclic aromatic hydrocarbon Aryl hydrocarbon hydroxylase Ultimate carcinogen

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Tobacco chewing →N’-Nitrosonornicotine →Directly affect on the oral mucosa (Tobacco mixed with saliva) Lime in betel quid → which allow direct access of carcinogen

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Arecoline → Aricodene (Potent stimulator of fibroblast proliferation and collagen synthesis) Hydrolysed by slaked lime

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Betel nut chewing may be important factor in the etiology of OSMF Betel nut extracts → Flavanoids and tannins (make more resistant to degradation by collagenase resulting in accumulation of collagen) Alkaloid component (Arecoline) → increase fibroblast proliferation and collagen synthesis

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(2) Local Irritants Capsaicin (active irritant in chillies) Spicy foods and alcohol

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(3) Autoimmunity In HLA-DR3 antigen (+) ce of serum immunoglobulins and autoantibodies OSMF (like scleroderma) Autoimmune basis

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(4) Genetic Alterations Almost all carcinogenic agents whether physical (radiation), chemical or infections (viruses) act as mutagens. They change structure of genetic material producing point mutations, deletion or insertions (mutation with sudden non-inherited changes of characteristics).

(5) Immunological Factors : 

(5) Immunological Factors Prolong immunosuppression can cause likelihood of malignant transformation because Helper T-cell play a vital role in functional differentiation of B-cells and production of interleukin-2 Decreased interleukin 2 production →↓ cellular & humoral immune response → prone to OSMF High levels of circulating immune complex (CIC) seen in OSMF

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(6) Nutritional Factors Iron metabolism is important in maintaining the health of the oral mucosa and upper GI tract Precondition of oral mucosa, chronic deficiency of iron & vitamin B complex acts as important role

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Kelly Paterson Chronic dysphagia or (sideropenic dysphagia) Plummer Vinson Syndrome + Iron deficiency anaemia + Glossitis OSMF may be considered as an analog of Plummer Vision Syndrome (Ramanathan) Folic acid, pyridoxine and Vit: B12, Vit: A and beta carotene deficiencies

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(7) Candidiasis In fungal infection → Yeasts → produce carcinogen mainly nitrosamine → malignant transformation(+)

CLINICAL FEATURES : 

CLINICAL FEATURES The onset is insidious over 2-5 years period Prodromal symptoms include; burning sensation in the mouth when consuming spicy food appearance of blister especially in the palate; ulceration or generalized inflammation of the oral mucosa excessive salivation; defective gustatory sensation & dryness of the mouth

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Early stage → Focal vascular dilatations clinically manifests as petechiae (may be vascular response due to hypersensitivity of oral mucosa to some irritants like chilli) Petechiae were observed mostly in the tongue followed by labial and buccal mucosa with no sign of blood dyscrasia or systemic disorders As the disease progresses, oral mucosa become blanched and slightly opaque and white thick fibrous band appear

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Oral mucosa is symmetrically involved & fibrous band in the oral mucosa run in vertical direction Severe cases →Deviation of uvula (+) Inability to whistle or blow out a candle Difficulty in swallowing

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Pterygomandibular raphe involvement (+)→ Limitation of mouth opening (+) Most of the patient experience a protracted period of stomatitis and/or glossitis with remission and exacerbation If fibrosis involves pharynx→ patient experience referred pain in ear Nasal voice as one of the later signs in some patients (MILLARD)

HISTOLOGICAL FEATURES : 

HISTOLOGICAL FEATURES Pathological alteration in OSMF begins in lamina propria & epithelium responds only secondary to it EPITHELIUM Epithelial atrophy – one of the marked changes in OSMF (or) Predominantly hyperplastic epithelium (1) & (2) → depend upon the cases & sites of biopsies Orthokeratosis (palate) or parakeratosis (buccal mucosa)

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CONNECTIVE TISSUES Homogenization and hyalinization of collagen fiber bundles Narrowing of the smaller vessels appears first in the oral cavity and gradually spreads to deeper vessels Perivascular round cell infiltration predominantly lymphocytes and plasma cells Degeneration of muscles in deeper connective tissue layer

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Earlier stages → mast cells (+) Obliterated blood vessels and capillaries Biological studies Blood chemistry and haematological variations vit B12 , folate and iron deficiencies

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↑ESR Anaemia Significant haematological Eosinophilia Abnormalities ↑ T.globulin ↓Serum iron ↑ Serum mucoproteins and mucopolysaccharides

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Iron-deficiency anemia appear to be one of the causes and not the effect of disorder Immunological studies ↑ serum levels of IgA, IgD and IgE

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Cytogenetics Peripheral blood of OSMF patient → ↑ ed SCE (sister chromatid exchange) MALIGNANT TRANSFORMATION Frequency of malignant change in patient’s with OSMF → 3-6%

MANAGEMENT : 

MANAGEMENT (1) PREVENTIVE MEASURE (2)MEDICAL CONSERVATIVE TREATMENT (3) SURGICAL MANAGEMENT (FOR ADVANCED CASES)

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(1) PREVENTIVE MEASURE Reduction or even elimination of areca nut chewing Abstaining from ingestion of suspected irritant: such as chillies, tobacco, pan ...etc Maintenance of proper oral hygiene Vitamin supplement

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Well-balanced diet Long term follow-up at short interval Public information about tobacco habits & Warning signs for oral cancer

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(2) MEDICAL CONSERVATIVE TREATMENT Vitamin B complex Nutritional support High protein & calories Iron

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Immunomodulatory Drugs (a) Local and systemic application of glucocorticoids Glucocorticoid Act as immunosuppressive agent ▼Fibrosis by decreasing fibroblastic proliferation and collagen deposition

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(b) Physiotherapy Hot rinses - Heat in the form of Lukewarm water Microwave (or) Short wave diathemy -Forceful opening of mouth Satisfactory results(++)

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(c) Local drug therapy Dexa methasone/steroids (i) Local injection of Hyaluronidase Placental extract (aqueous solution of human placenta)

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Submucosal Dexamethasone 2 part of Injection 4mg/ml + hyaluronidase (800 USP unit/ml) diluted in 10ml of 2% xylocaine

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By means of gauge 27 dental needle not more than 0.2ml solution for period of 20 weeks * (Massaging the cheeks with mouth closed. Asking the patient to perform mouth opening exercises for 30min after the submucosa injection)

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Hyaluronidase by breaking down ↓ viscosity Hyaluronic acid of intercellular ground substances Decreased collagen formation

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Placental extract anti inflammatory action (+) and analgesic effect (+) ↑ed Blood circulation and tissue vascularity Lowered immune response Produce metabolic degenerative condition

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Steroids → combined use of local and systemic administration of hydrocortisone (intralesional injection of kenakog) Chymotrypsin → Act as proteolytic and anti-inflammatory agent

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(d) Combined therapy Peripheral vasodilator + vit: D, E, B complex + placental extract + steroids (local & systemic) + Physiotherapy → 62% success rate (e) Submucosal injection of fibrinolysin and gold

(3) SURGICAL MANAGEMENT (FOR ADVANCED CASES) : 

(3) SURGICAL MANAGEMENT (FOR ADVANCED CASES) Teeth needing extraction should be dealt before commencement of any treatment/ management of OSMF Submucosal resection of fibrotic band replaced by partial –thickness skin graft or mucosal graft Recently →Surgical excision of fibrous bands with submucosal replacement of fresh human placenta graft follow by local injections of Dexamethasone

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THE END