OSMF- Immunopatho- histo relation

The possible etiological factors to date are areca nut, capsaicin in

chillies, micronutrient deficiencies of iron, zinc and essential vitamins. A
possible autoimmune disease with various auto-antibodies and genetic
predisposition with specific human leukocyte antigen (HLA) has also been
proposed. However, it is clear that the regular use of areca nut/betel nut is
the major etiological factor.
Immunopathogenesis
The disease is multifactorial but the exact pathogenesis is not wellestablished. The mechanisms responsible for the pathogenesis are increased
collagen accumulation, increased expression of fibrogenic cytokines, genetic
polymorphisms and autoimmunity.
The increased collagen accumulation results from increased collagen
production and stabilization or decreased breakdown of collagen.
Pathogenesis involves subepithelial inflammatory reaction and fibrosis in the
oral mucosa.
Due to chronic irritation from areca nut chewing, T cells and
macrophages are activated at the site which increases cytokines (IL-6,
interferon ) and transforming growth factor (TGF-) at the site. Lastly
OSMF is also thought to be an autoimmune disorder.
Histopathology
In the initial pathology of OSMF, collagen bundles with early
hyalinization are seen and inflammatory infiltrate becomes more chronic
consisting of lymphocytes and plasma cells. Epithelium may show atrophic
changes and dysplastic features. In more advanced stages, OSMF is
characterized by formation of thick bands of collagen fibers and
hyalinization extending deep into the submucosal tissues and decreased
vascularity.

Clinical staging - Most recently proposed classification is by More et al. in

2012.
Stage 1: (S1) Stomatitis and/or blanching of the oral mucosa
Stage 2: (S2) Presence of palpable fibrous bands in buccal mucosa
and/or oropharynx, with/without stomatitis
Stage 3: (S3) Presence of palpable fibrous bands in buccal mucosa
and/or oropharynx and in any other parts of oral cavity, with/without
stomatitis
Stage 4: (S4) (A) Any one of the above stage, along with other
potentially malignant disorders, e.g. oral leukoplakia, erythroplakia, etc.,
(B) Any one of the above stage along with oral carcinoma.
Functional staging
M1: Inter-incisal mouth opening up to or >35 mm
M2: Inter-incisal mouth opening between 25 mm and 35 mm
M3: Inter-incisal mouth opening between 15 mm and 25 mm
M4: Inter-incisal mouth opening <15 mm
Proposed Clinico-Pathological classification of OSMF depending on
review of different classification systems (1966 2015)
Stage I: Clinically: Patients complains of burning sensation and altered taste
perception. Opening of mouth can be scored as 36mm to 40mm. When
related to buccal mucosa symptoms are not present.
Histopathlogically: Collagen fibres are finely spread with noticeable edema
with huge sum of plump young fibroblasts along with abundant cytoplasm.
In the connective tissue stroma inflammatory cells composed mainly of
lymphocytes and rare eosinophils. Overlying epithelium is normal.
Stage II: Clinically: Patient Complains of burning sensation, increased
sensitivity to spicy food, white bands like lesions can be seen on any one
2

anatomical site in the oral cavity. Mouth opening can be scored as 32mm to
36mm.
Histopathologically: Collagen is still separate and thick with separate
bundles. Juxta epithelial hyalinization is present. It contains young
fibroblasts in moderate count and dilated blood vessels. Inflammatory cells
consist of lymphocytes and few eosinophils but rarely contain plasma cells.
The epithelium shows flattening or shortened epithelial rete pegs with
varying degree of keratinisation.
Stage III: Clinically: Patient complains of severe burning sensation, when
they take hot or spicy food. Extensive fibrous white bands on the buccal
mucosa can be palpated with difficulty in mastication. Mouth opening can
be scored 28mm to 32mm.
Histolopathologically: Thick collagen bundles separated by slight edema.
Juxta epithelial hyalinization is present. Connective tissue stroma consists of
conjugated blood vessels, mature fibroblasts, scanty cytoplasm and spindle
shaped nuclei. Inflammatory cells are mainly neutrophils and plama cells.
Muscle fibers are thick and collagen fibers are dense. The epithelium is
atrophic with loss of rete pegs.
Stage IV: Clinically: Patient is anemic and malnourished due to poor
nutrition and inability to open mouth. Severe trismus with fibrous white
band extends all the mouth over the prominent anatomical sites. Mouth
opening can be scored as less than 10mm.
Histopathologically: Complete hyalinised collagen is present. This collagen
is in the form of smooth sheets. Edema is not present in this stage.
Fibroblasts are absent. Connective tissue stroma consists of blood vessels
which are destroyed or restricted. Inflammatory cells are lymphocytes and
plasma cells. They also show mild to moderate atypia and severe
degeneration of muscle fibers.

Management of OSMF
Complete stoppage or even reduction of the habit of areca nut
chewing is the most important aspect of management. The management
suggested for the OSMF is as follows.
Nutritional support - Micronutrients, high proteins, calories and vitamins
are the main nutritional support required for the management of the
condition.
Immunomodulatory drugs - Local and systemic glucocorticoids and
placental extracts are the most commonly used. These also prevent or
suppress inflammatory reaction by decreasing fibroblastic proliferation and
deposition of collagen, thereby decreasing fibrosis.
Physiotherapy - This includes measures such as forceful mouth opening,
blowing and heat therapy. These measures have been commonly used and
the results have been described as satisfactory.
Local drug
extract have
collagenase,
break down
formation.

delivery - Local injection of corticosteroids and placental

also been tried, in addition to hyaluronidase, dexamethasone,
interferon-, antifibrotic cytokine and like substances which
intercellular cement substances and also decreases collagen

Combined therapy - Combined therapy of peripheral vasodilators (nylidrin

hydrochloride), vitamin D, E and B complex, placental extract, local and
systemic corticosteroids and physiotherapy can produce a high success rate
in OSMF management.
Surgical management - Measures such as forcing the mouth open and
cutting the fibrotic bands have resulted in more fibrosis and disability.
Submucosal resection of fibrotic bands and replacement with a partial
thickness skin or mucosal graft has been attempted. Procedures such as
bilateral temporalis myotomy have also been tried.