Oral submucous fibrosis

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Oral submucous fibrosis
Other namesOSMF or OSF
Specialty Oral medicine and Dentistry and Oral Pathology

Oral submucous fibrosis (OSF) is a chronic, complex, premalignant (1% transformation risk) condition of the oral cavity, characterized by juxta-epithelial inflammatory reaction and progressive fibrosis of the submucosal tissues (the lamina propria and deeper connective tissues). As the disease progresses, the oral mucosa becomes fibrotic to the point that the person is unable to open the mouth. [1] [2] The condition is remotely linked to oral cancers and is associated with the chewing of areca nut and/or its byproducts, commonly practiced in South and South-East Asian countries. [3] The incidence of OSF has also increased in western countries due to changing habits and population migration. [4]

Contents

Definitions

Symptoms

In the initial phase of the disease, the mucosa feels leathery with palpable fibrotic bands. The oral mucosa loses resiliency in the advanced stage and becomes blanched and stiff. This blanched and stiff mucosa is considered to lead to a progressive reduction in mouth opening but seems to be an oversimplification of the pathology. The degree of mouth opening is also determined by the severity of oral symptoms, such as recurring or persistent glossitis and stomatitis, a fact that many researchers ignore. This phenomenon is explained by the term Reflectory Trismus, where the above symptoms dictate the degree of mouth opening through activation of the 5th and 9th cranial nerves. However, muscle damage and fibrosis play a larger contributory role. [9] The condition is believed to begin in the posterior part of the oral cavity and gradually spread outward. The premise posterior to the anterior progression of oral submucous fibrosis has been recently rebutted based on several reports stating that the disease may be restricted to the anterior part of the oral cavity without involvement of posterior parts; the sites are dictated by the manner of use anterior areas of the oral cavity when spitting and posterior when swallowed. [10]

Other features of the disease include:

Cause

Pathogenesis

"Exposure to areca nut (Areca catechu) containing products with or without tobacco (ANCP/T) is currently believed to lead to OSF in individuals with genetic immunologic or nutritional predisposition to the disease.". [11] On the other hand, reduced CD1a+ Langerhans cells and CD207+ dendritic cells indicate evolving immunosuppression in OSF and its progression to OSCC. [12]

This hypersensitivity reaction results in a juxta-epithelial inflammation that leads to increased fibroblastic activity and decreased breakdown of fibers. The fibroblasts are phenotypically modified, and the fibers they form are more stable, produce thicker bundles that progressively become less elastic. once the original loosely arranged fibrous tissue is replaced by the ongoing fibrosis, the movability of the oral tissues is reduced, there is loss of flexibility and reduced opening of the mouth. These collagen fibers are non degradable and the phagocytic activity is minimized. The role of pure capsaicin in the etiology and pathogenesis of oral submucous fibrosis has been debunked, as its has been shown to have antifibrotic and anticancer effects. [13] Mosqueda-Solís in their Systematic review have shown anticancer activity of capsaicin on oral cancer. [14] It has been shown by computational biology, capsaicin hinders the collagen fibre formation. [13] Moreover, capsaicin has been shown to cause the degradation of collagen I by activation of MMP1 through TRPV1 channels. [15]

According to a 2015 cross-sectional study, the time taken for return of salivary pH to baseline levels after chewing areca-nut-containing mixtures is significantly longer in habitual users with OSF when compared to unaffected users. [11] Prolonged alkaline pH induces death of the fetal fibroblast type and replacement by a profibrotic fibroblast. [11] The patterns of intraoral fibrotic bands produced by alkaline chemical injury mimic those produced by areca nut chewing. [16] Sharma et al. have equated the pathogenesis of OSF to an over-healing wound, to explain its evolution as well as malignant transformation. [16] [17] Given that OSF is an overhealing wound, Choudhari et al. have recently implicated that factor XIIIa (the last factor in the coagulation pathway) plays a critical role in the development of fibrosis in OSF and that there is a strong correlation between factor XIIIa and increasing grades of OSF in their study. [18] Incidentally, Sharma et al. in 2018 had already proposed an important role of factor XIIIa in the pathogenesis of OSF, by promoting the generation of fibrin degradation products (FDP). [16] Literature is replete with patients with OSF having FDPs in their blood, and this can be considered as a proof for the role of factor XIIIa in the pathogenesis of OSF. [16]

Increased mechanical stiffness through YAP/TAZ pathway accelerates the malignant transformation of OSF. [19] The atrophic epithelium in OSF has been attributed to the senescence of the basal stem cell layer and the development of hyperplastic epithelium through senescence escape. [17] [20] The role of senescence in pathogenesis of oral submucous fibrosis has been supported by further research. [21] [22] [23]

Diagnosis

Classification

Oral submucous fibrosis is clinically divided into three stages: [24]

Khanna and Andrade in 1995 developed a group classification system for the surgical management of trismus: [25]

Treatment

Biopsy screening, although necessary, is not mandatory; most dentists can visually examine the area and proceed with the proper course of treatment.[ citation needed ]

Treatment includes:

Treatment also includes following:

The treatment of patients with oral submucous fibrosis depends on the degree of clinical involvement. [33] 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. Severe oral submucous fibrosis is irreversible. Moderate oral submucous fibrosis is reversible with cessation of habit and mouth opening exercise. Current modern day medical treatments can make the mouth opening to normal minimum levels of 30 mm mouth opening with proper treatment.

Research

Scientists have proven that intralesional injection of autologous bone marrow stem cells is a safe and effective treatment modality in oral submucosal fibrosis. It has been shown autologous bone marrow stem cell injections induces angiogenesis in the lesion area, which in turn decreases the extent of fibrosis, thereby leading to significant increase in mouth opening. [34] [35]

Epidemiology

The incidence of the disease is higher in people from certain parts of the world including South and South East Asian, South Africa and the Middle Eastern countries. [36] In 1996, the number of cases were estimated around 2.5 million worldwide but there is no population-base data as it is not notifiable disease. In India, the prevalence is estimated 0.2–2.3% in males and 1.2–4.6% in females; with age range of 11 to 60 years. It is widely reported in South Asian diaspora in Europe, North America and South Africa. [37]

History

In 1952, T. Sheikh coined the term distrophica idiopathica mucosa oris to describe an oral fibrosing disease he discovered in five Indian women from Kenya. [38] S. G. Joshi subsequently coined the termed oral submucous fibrosis (OSF) for the condition in 1953. [39]

See also

Related Research Articles

<span class="mw-page-title-main">Areca nut</span> Fruit of the areca palm chewed as a stimulant

The areca nut or betel nut is the fruit of the areca palm. The palm is originally native to the Philippines, but was carried widely through the tropics by the Austronesian migrations and trade since at least 1500 BCE due to its use in betel nut chewing. It is widespread in cultivation and is considered naturalized in much of the tropical Pacific, South Asia, Southeast Asia, and parts of east Africa. It is not to be confused with betel leaves that are often used to wrap it. The practice of betel nut chewing, often together with other herbs as a stimulant drug, dates back thousands of years, and continues to the present day in many countries.

<span class="mw-page-title-main">Trismus</span> Condition of limited jaw mobility

Trismus is a condition of restricted opening of the mouth. The term was initially used in the setting of tetanus. Trismus may be caused by spasm of the muscles of mastication or a variety of other causes. Temporary trismus occurs much more frequently than permanent trismus. It is known to interfere with eating, speaking, and maintaining proper oral hygiene. This interference, specifically with an inability to swallow properly, results in an increased risk of aspiration. In some instances, trismus presents with altered facial appearance. The condition may be distressing and painful. Examination and treatments requiring access to the oral cavity can be limited, or in some cases impossible, due to the nature of the condition itself.

<span class="mw-page-title-main">Mouth ulcer</span> Sore on the mucous membrane of the oral cavity

A mouth ulcer (aphtha), or sometimes called a Canker sore, is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause. Rarely, a mouth ulcer that does not heal may be a sign of oral cancer. These ulcers may form individually or multiple ulcers may appear at once. Once formed, an ulcer may be maintained by inflammation and/or secondary infection.

<span class="mw-page-title-main">Oral cancer</span> Cancer of the lining of the lips, mouth, or upper throat

Oral cancer, also known as oral cavity cancer, tongue cancer or mouth cancer, is a cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless red or white patch, that thickens, gets ulcerated and continues to grow. When on the lips, it commonly looks like a persistent crusting ulcer that does not heal, and slowly grows. Other symptoms may include difficult or painful swallowing, new lumps or bumps in the neck, a swelling in the mouth, or a feeling of numbness in the mouth or lips.

<span class="mw-page-title-main">Leukoplakia</span> Medical condition

Oral leukoplakia is a potentially malignant disorder affecting the oral mucosa. It is defined as "essentially an oral mucosal white/gray lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a gray patch or plaque that develops in the oral cavity and is strongly associated with smoking. Leukoplakia is a firmly attached white patch on a mucous membrane which is associated with increased risk of cancer. The edges of the lesion are typically abrupt and the lesion changes with time. Advanced forms may develop red patches. There are generally no other symptoms. It usually occurs within the mouth, although sometimes mucosa in other parts of the gastrointestinal tract, urinary tract, or genitals may be affected.

<span class="mw-page-title-main">Lichen planus</span> Human chronic inflammatory disease

Lichen planus (LP) is a chronic inflammatory and autoimmune disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, but is named for its appearance. It is characterized by polygonal, flat-topped, violaceous papules and plaques with overlying, reticulated, fine white scale, commonly affecting dorsal hands, flexural wrists and forearms, trunk, anterior lower legs and oral mucosa. The hue may be gray-brown in people with darker skin. Although there is a broad clinical range of LP manifestations, the skin and oral cavity remain as the major sites of involvement. The cause is unknown, but it is thought to be the result of an autoimmune process with an unknown initial trigger. There is no cure, but many different medications and procedures have been used in efforts to control the symptoms.

<span class="mw-page-title-main">Fibrosis</span> Excess connective tissue in healing

Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue.

<span class="mw-page-title-main">Pulmonary fibrosis</span> Disease that causes scarring of the lungs

Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failure, pneumothorax, and lung cancer.

<i>Areca catechu</i> Species of palm

Areca catechu is a species of palm native to the Philippines cultivated for areca nuts. It was carried widely through the tropics by the Austronesian migrations and trade since at least 1500 BCE due to its use in betel nut chewing. It is widespread in cultivation and is considered naturalized in Malaysia, Indonesia, New Guinea, Taiwan, Madagascar, Cambodia, Laos, Myanmar, Thailand, Vietnam, southern China, India, Nepal, Bangladesh, the Maldives, Sri Lanka, parts of the Pacific Islands, and also in the West Indies.

<span class="mw-page-title-main">Precancerous condition</span> Condition or cell change indicating increased cancer risk

A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased risk of developing into cancer. Some of the most common precancerous conditions include certain colon polyps, which can progress into colon cancer, monoclonal gammopathy of undetermined significance, which can progress into multiple myeloma or myelodysplastic syndrome. and cervical dysplasia, which can progress into cervical cancer. Bronchial premalignant lesions can progress to squamous cell carcinoma of the lung.

The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed lamina propria. The oral cavity has sometimes been described as a mirror that reflects the health of the individual. Changes indicative of disease are seen as alterations in the oral mucosa lining the mouth, which can reveal systemic conditions, such as diabetes or vitamin deficiency, or the local effects of chronic tobacco or alcohol use. The oral mucosa tends to heal faster and with less scar formation compared to the skin. The underlying mechanism remains unknown, but research suggests that extracellular vesicles might be involved.

<span class="mw-page-title-main">Arecoline</span> Stimulant alkaloid

Arecoline is a nicotinic acid-based mild parasympathomimetic stimulant alkaloid found in the areca nut, the fruit of the areca palm. It is an odourless oily liquid. It can bring a sense of enhanced alertness and energy along with mild feelings of euphoria and relaxation.

<span class="mw-page-title-main">Verrucous carcinoma</span> Medical condition

Verrucous carcinoma (VC) is an uncommon variant of squamous cell carcinoma. This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dipper's cancer".

<span class="mw-page-title-main">Acinic cell carcinoma</span> Medical condition

Acinic cell carcinoma is a malignant tumor representing 2% of all salivary tumors. 90% of the time found in the parotid gland, 10% intraorally on buccal mucosa or palate. The disease presents as a slow growing mass, associated with pain or tenderness in 50% of the cases. Often appears pseudoencapsulated.

Giant-cell fibroma is a benign localized fibrous mass. It often mimics other fibroepithelial growths and can be distinguished by its histopathology. The exact cause of giant-cell fibromas is unknown however there is no evidence to show that it can be caused by irritation. Giant-cell fibromas can be removed by surgical incision, electrosurgery, or laser excision.

Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic cardiac muscle is stiffer and less compliant and is seen in the progression to heart failure. The description below focuses on a specific mechanism of valvular pathology but there are other causes of valve pathology and fibrosis of the cardiac muscle.

<span class="mw-page-title-main">Gingival enlargement</span> Increase in size of the gums

Gingival enlargement is an increase in the size of the gingiva (gums). It is a common feature of gingival disease. Gingival enlargement can be caused by a number of factors, including inflammatory conditions and the side effects of certain medications. The treatment is based on the cause. A closely related term is epulis, denoting a localized tumor on the gingiva.

<span class="mw-page-title-main">Desmoplasia</span> Growth of fibrous or connective tissue

In medicine, desmoplasia is the growth of fibrous connective tissue. It is also called a desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.

Oral pigmentation is asymptomatic and does not usually cause any alteration to the texture or thickness of the affected area. The colour can be uniform or speckled and can appear solitary or as multiple lesions. Depending on the site, depth, and quantity of pigment, the appearance can vary considerably.

Smokeless tobacco keratosis (STK) is a condition which develops on the oral mucosa in response to smokeless tobacco use. Generally it appears as a white patch, located at the point where the tobacco is held in the mouth. The condition usually disappears once the tobacco habit is stopped. It is associated with slightly increased risk of mouth cancer.

References

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  30. ↑ Haque MF, Meghji S, Nazir R, Harris M (January 2001). "Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis". Journal of Oral Pathology & Medicine. 30 (1): 12–21. doi:10.1034/j.1600-0714.2001.300103.x. PMID   11140895.
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  34. ↑ Sankaranarayanan S, Padmanaban J, Ramachandran CR, Manjunath S, Baskar S, Senthil Kumar R, et al. (June 2008). Autologous Bone Marrow stem cells for treatment of Oral Sub-Mucous Fibrosis - a case report. Sixth Annual Meeting of International Society for Stem Cell Research (ISSCR). Philadelphia.
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  36. ↑ Oral Submucous Fibrosis at eMedicine
  37. ↑ Rao NR, Villa A, More CB, Jayasinghe RD, Kerr AR, Johnson NW (2020-01-01). "Oral submucous fibrosis: A contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management". Journal of Otolaryngology - Head & Neck Surgery. 49 (1): 3. doi: 10.1186/s40463-020-0399-7 . ISSN   1916-0216. PMC   6951010 . PMID   31915073.
  38. ↑ Hetland G, Johnson E, Lyberg T, Bernardshaw S, Tryggestad AM, Grinde B (October 2008). "Effects of the medicinal mushroom Agaricus blazei Murill on immunity, infection and cancer". Scandinavian Journal of Immunology. 68 (4): 363–370. doi: 10.1111/j.1365-3083.2008.02156.x . PMID   18782264.
  39. ↑ Joshi SG (1952). "Fibrosis of the palate and pillars". Indian Journal of Otolaryngology. 4 (1): 1–4.
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