Submucous fibrosis

Submucous fibrosis is caused by betel use

INTRODUCTION

This chapter should be read along with Ch. 25.

Oral submucous fibrosis (OSMF) is a chronic disorder seen only in persons who chew betel (Areca catechu) nuts, pan masala or gutkha – and is characterized by tightening of the buccal, and sometimes palatal and lingual mucosae, causing trismus.

INCIDENCE

4/1 000 adults in rural India.

AETIOLOGY AND PATHOGENESIS

The basic issue in OMSF appears to be an increase in submucosal collagen, for which there may be some genetic predisposition. Patients have an increased frequency of HLA-A10, HLA-B7, and HLA-DR3. Further, the HLA class I chain-related gene A (MICA), particularly the phenotype frequency of allele A6 of MICA is increased in OSMF, expressed by keratinocytes and other epithelial cells and interacts with gamma/delta T cells in the submucosa. Increased levels of pro-inflammatory cytokines and reduced antifibrotic interferon gamma may be central to the pathogenesis.

The lesions of OSMF appear to arise due to exposure to areca nut constituents which act by increasing collagen cross-linking or other effects. One betel nut alkaloid, arecoline, stimulates production of:

collagen

interleukin 6

keratinocyte growth factor-1

insulin-like growth factor-1

cystatin C (a protein up-regulated in a variety of fibrotic diseases)

tissue inhibitor of matrix metalloproteinases (TIMP).

Arecoline inhibits matrix metalloproteinases (MMPs – particularly MMP-2), and chewing areca quid may also activate NF-κB expression, thereby further stimulating collagen fibroblasts. Flavonoids, catechin, tannin and possibly copper in betel nuts may cause collagen fibres to cross-link, making them less susceptible to collagenase degradation.