Oral Submucous Fibrosis

INTRODUCTION-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.The buccal mucosa is the most commonly involved site, but any part of the oral cavity can be involved, even the pharynx.

The condition is well recognized for its malignant potential and is particularly associated with areca nut chewing, the main component of betel quid.

PATHOGENESIS AND ETIOLOGY- 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.

The role of the constituents of areca nut in the pathogenesis of OSF has been studied in detail over last two decades. It is apparent that fibrosis and hyalinization of subepthelial tissues account for most of the clinical features encountered in this condition. Moreover, substantial amount of research on elucidating the etiology and pathogenesis appear to have been focused on changes in the extracellular matrix (ECM). It is logical to hypothesize that the increased collagen synthesis or reduced collagen degradation as possible mechanisms in the development of the disease. There are numerous biological pathways involved in the above processes and, it is likely that the normal regulatory mechanisms are either down regulated or up regulated at different stages of the disease.

Quid has been defined as a substance or mixture of substances placed in the mouth or chewed and remaining in contact with the mucosa usually containing one or both of the two basic ingredients tobacco and/or areca nut in raw or any manufactured or processed form .The major areca nut alkaloids are arecoline, arecadine, arecolidine, guyacoline and guacine . SYMPTOMS-

Symptoms of oral submucous fibrosis include the following:

• 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)
  STAGES-Oral submucous fibrosis is clinically divided into 3 stages, and the physical findings vary accordingly, as follows:
  • 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 of individuals with oral submucous fibrosis.
    • Speech and hearing deficits may occur because of involvement of the tongue and the eustachian tubes.

    HISTOLOGIC FINDINGS- Histologic findings vary according to the stage of the disease.

    Very early stage

    Fine fibrillar collagen, marked edema, large fibroblasts, dilated and congested blood vessels, and inflammatory infiltrates (primarily polymorphonuclear leukocytes and eosinophils) are found.

    Early stage

    Early hyalinization is characterized by thickened collagen bundles, moderate numbers of fibroblasts, and inflammatory cells (primarily lymphocytes, eosinophils, and plasma cells).

    Moderately advanced and advanced stages

    Dense bundles and sheets of collagen, thick bands of subepithelial hyalinization extending into the submucosal tissues (replacing fat or fibrovascular tissue), decreased vascularity, no edema, and inflammatory cells (lymphocytes and plasma cells) are found.

    Oral submucous fibrosis is generally characterized by diffuse hyalinization of the subepithelial stroma with pigment incontinence from the overlying epithelial melanin.Other histologic findings include an atrophic epithelium and intercellular edema, with or without hyperkeratosis, parakeratosis, or orthokeratosis; epithelial dysplasia; squamous cell carcinoma histologically identical to typical squamous cell carcinomas; chronic inflammation and fibrosis in the minor salivary glands in the area of quid placement; and atrophy of the underlying muscle.

    Ultrastructural changes in oral submucous fibrosis include an increase in collagen type I; however, fibrils retain the normal structure.

    STAGING -In addition to the above clinical staging, in 1995 Khanna and Andrade developed a group classification system for the surgical management of trismus.

    
    

    • Group I: This is the earliest stage and is not associated with mouth opening limitations. It refers to patients with an interincisal distance of greater than 35 mm.
    • Group II: This refers to patients with an interincisal distance of 26-35 mm.
    • Group III: These are moderately advanced cases. This stage refers to patients 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.
      TREATMENT-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 following :
      • 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, 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.
      • 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.
      • 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.
      • Lycopene(anti oxidant): Newer studies highlight the benefit of this oral nutritional supplement at a daily dose of 16 mg.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.
      • Pentoxifylline:(vasodilator)-Methylxanthine derivative that has vasodilating properties and may increase mucosal vascularity.
      • Multivitamins