Oral submucous fibrosis: A report of two pediatric cases and a brief review

Abstract

Oral submucous fibrosis is a chronic debilitating disorder which is usually seen in adults with areca nut chewing habit. A rapid upsurge in the popularity of commercial areca nut products, especially among the younger generation, is a cause of grave concern, as satisfactory management is still lacking. Hereby, two pediatric cases of oral submucous fibrosis are reported.

Introduction

Oral submucous fibrosis (OSMF) is a chronic disorder characterized by progressive fibrosis of the lining mucosa of the upper digestive tract involving the oral cavity, oropharynx, and frequently the upper third of the esophagus, resulting in intolerance to spicy foods, a burning sensation in the mouth, xerostomia, and limitation of mouth opening, tongue mobility, swallowing, or phonation. 

It mostly occurs in Asian countries, where chewing betel quid (BQ; contains areca nut, tobacco, slaked lime, or other spices) and other commercial preparations of areca nut in attractive pouches is popular. Epidemiologic surveys in India show the rate of prevalence to be about 0.5%. Persons between 20 and 40 years of age are most commonly affected, with a female: male ratio of 3:1. Morbidity of OSMF among BQ users is about 3.2%  and it has a malignant transformation rate in the range of 7-13%. 

Histologically, OSMF shows the characteristic features of juxta-epithelial fibrosis, mostly along with atrophy of the overlying epithelium, accumulation of hyalinized collagen beneath the basement membrane, and a progressive loss of vascularity.  

The pathogenesis of the disease is not well established, but is believed to be multifactorial. Various mechanisms suggested include: 1) clonal selection of fibroblasts with a high amount of collagen production during long-term exposure to areca nut,  2) stabilization of collagen structure by catechin and tannins from BQ, 3) production of stable collagen (type I) by OSF fibroblasts, 4) increase in collagen cross-linking by up-regulation of lysyl oxidase, 5) deficient collagen phagocytosis, and 6) micronutrient and vitamin deficiencies.

Mainly adults are affected and it is uncommon in the pediatric age group. Only limited number of pediatric cases have been reported in the literature. A youngest case of 4-year-old girl has been reported in the literature.  Hereby, two cases of OSMF are reported, highlighting the potential danger of involvement of the pediatric age group from "Pouch Culture."

Case Reports

Case 1

A 10-year-old local factory worker boy reported with difficulty in opening mouth and taking spicy food for the last 3 months. Both his parents were laborers. He was reportedly chewing gutkha two to three times a day for the last 1 year, as his colleagues at the local factory encouraged him to take the habit. On examination, reduced inter-incisal distance (IID=1.5 cm), and generalized blanched oral mucosa involving the soft palate and the anterior faucial pillars were observed (Figure 1) and (Figure 2). On palpation, loss of normal resilience and pliability of the mucosa with dense fibrotic bands were observed in the buccal mucosa bilaterally. Routine hematological investigations were within the normal range except for the hemoglobin which was 9.1 gm%. A clinical diagnosis of OSMF was confirmed and the boy was prescribed oral iron supplementations, vitamin A, and zinc acetate after counseling to completely quit the habit, but unfortunately the patient failed to report for further follow-up.

Figure 1: Intraoral view showing difficulty in mouth opening with blanching of oral mucosa, generalized stains

Figure 2: Inter-incisal distance=1.5 mm

Case 2

A 12-year-old girl complained of burning sensation on having food for the last 3-4 years, which has aggravated recently. The girl's grandmother was a habitual pan masala chewer and unaware of the consequences, used to give her granddaughter a small amount of it almost daily since she was 5 years old. General physical examination revealed normal general condition.

On oral examination, generalized blanched mucosa was observed with loss of elasticity and presence of vertical fibrous bands bilaterally in the buccal mucosa. The uvula was shrunken and the tongue was atrophic. Few retained deciduous root stumps and generalized tobacco stains were observed on dental hard tissue examination (Figure 3). The IID was 1.9 cm (Figure 4). Routine hematological examination revealed nothing significant. A diagnosis of OSMF was established. Following the conservative line of treatment, biopsy was considered unnecessary as it adds to the discomfort for patient. Rebound fibrosis has also been reported in certain cases. The girl and her guardians were motivated to completely stop the habit and avoid spicy food. Oral prophylaxis and extraction of the retained root stumps was advised.

Figure 3: Shrunken uvula and generalized blanched mucosa

Figure 4: Pre-supplementation inter-incisal distance=1.9 mm


































The patient was administered vitamin A (25,000 IU OD) and zinc acetate syrup (5 ml bid) for 3 months. Warm saline rinses and mild mouth-opening exercises were advised along with regular check-up after 15 days followed by 1 month interval.

A relief from burning sensation was reported on the first recall visit itself, i.e. after 15 days. Mouth opening also improved slowly, and after the 3 months regimen, the IID was reported to be 2.5 cm (Figure 5). Only mild improvement was noticed in the blanching of the oral mucosa. The patient was further advised vitamin B complex supplements every alternate day for the next one month along with warm saline rinses and is under regular follow-up.

Figure 5: Post-supplementation inter-incisal distance=2.4 mm

Discussion

OSMF is regarded as a collagen metabolic disorder with an overall increased collagen production and decreased collagen degradation resulting in increased collagen deposition in the oral tissues, and fibrosis due to alkaloid exposure. 

The list of treatment modalities is extensive and includes the use of micronutrients and minerals, CO2 laser, pentoxifylline, lycopene, interferon gamma, turmeric, hyalase, chymotrypsin, and placental extracts. As fibrosis cannot be reversed when mouth opening is severely reduced, surgical interventions such as myotomy, coronoidectomy, and excision of the fibrotic bands have also been reported in the literature. Alternatively, procedures such as insertion of stent, physiotherapy, local heat therapy, and mouth-opening exercises with acrylic carrots and ice-cream sticks have been tried with variable success rates. 

Till today, no well-established treatment for OSMF exists and approaches using injections of steroids, chymotrypsin, hyaluronidase, or alcohol, and surgery using mucosal or non-vascularized split thickness grafts have not only been ineffective but have also often exacerbated the condition, with added scar tissue.  

Copper plays a pivotal role in the pathogenesis of OSMF. Copper released in high amounts from areca nut has been reported to up-regulate the enzyme lysyl oxidase in OSMF cases as copper is a ligand for the enzyme.  Zinc is an essential component of a large number of enzymes participating in the synthesis of carbohydrates, lipids, proteins, and nucleic acids, and also plays a central role in humoral and cellular immune system. Further, Di Silvestro et al. had reported that higher levels of dietary zinc reduce the bioavailability of copper at absorption stage. Vitamin A is an essential nutrient needed in small amounts by humans for normal functioning of the visual systems, growth and development, maintenance of epithelial integrity, and immune functions. So, based on the previous studies and our own institutional experience, a 3-month regimen of vitamin A and zinc acetate was prescribed with cessation of the habit and regular check-up. Improvement in burning sensation and an increase in mouth opening were observed after 3 months.

To conclude, the present drug treatments are empirical and symptomatic in nature. A combination of several drugs may play an important role in the treatment because it is a multifactorial disease. In the near future, younger ones may be affected more and an active preventive approach is required to limit the morbidity associated with the modern pouch culture.

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