red and white lesions of oral cavity

red and white lesions of oral cavity

1. RED AND WHITE LESIONS OF ORAL CAVITY BY Dr. REVATH VYAS PG III YEAR

2. Color of oral mucosa depends on… Orban’s Oral Histology & Embryology 11 th edition.

3. Hyper keratosis Acanthosis Intra and extracellular accumulation of fluid in the epithelium (i.e. Leukoedema ) Necrosis of the oral epithelium Microbes, particularly fungi, produce whitish pseudomembranes Reduced vascularity in the underlying lamina propria . Why abnormally white?

4. Why abnormally red ? Atrophic epithelium Reduction in the number of epithelial cells Increased vascularisation Blood vessel enlargement Presence of blood in the tissue Increased hemoconcentration Bengel, Veltman, Loevy, Taschini - Differential diagnosis of diseases of the oral mucosa Burket’s oral medicine – 10 th edn.

5. Causes of red lesions Crispian Scully - Oral & Maxillofacial Medicine; 2004.

6. CLASSIFICATIONS

7. CLASSFICATION ACCORDING TO Wood & Goaz , V edition

8. CLASSIFICATION ACORDING TO RAVI KIRAN ONGOLE 2 ND EDITION

9. CLASSFICATION ACCORDING TO BURKET’S 11 th edition

10. INFECTIOUS DISEASES ORAL CANDIDIASIS HAIRY LEUKOPLAKIA

11. ORAL CANDIDIASIS ( Candidosis , Moniliasis , Thrush) Opportunistic infection affecting the oral mucosa. Caused by the yeast candida albicans . Predisposing factors convert candida from the normal commensal flora (saprophytic stage) to a pathogenic organism (Parasitic stage ).

12. Etiology : Candida species responsible for candidal infections are c. albicans c. tropicalis and 80% of the species c. glabrata Yeasts penetration of epithelial cells is facilitated by their production of lipases

13. CLINICAL FINDINGS PSEUDOMEMBRANOUS CANDIDIASIS Acute form is recognized as classic candida infection Affects patients medicated with antibiotics, immunosuppressant drugs or a disease Oral lesions are soft, white, slightly elevated plaques occurring on the buccal mucosa, tongue, palate, gingiva and floor of the mouth. “ Curdly white” Plaques can be wiped away with guaze , leaves an inflamed, sometimes bleeding area. Clinical presentations of acute and chronic are indistinguishable. Chronic form associated with HIV infections and with steroid inhalers.

14. ERYTHEMATOUS CANDIDIASIS Previously referred as atrophic candidiasis (Antibiotic sore mouth or Antibiotic stomatitis) Occurs as a sequelae to a course of broad spectrum antibiotics, inhalation steroids smoking and diseases. Lesions appear red or erythematous May occur at any site Only variety of oral candidiasis, which is consistently painful.

15. CHRONIC PLAQUE-TYPE AND NODULAR CANDIDIASIS (Chronic Hyperplastic candidiasis ) Chronic-plaque type replaces candidal leukoplakia Characterized by a white plaque. Firm, white persistent plaques, usually on the lips, tongue and cheeks Chronic plaque-type and nodular candidiasis have been associated with malignant transformation.

16. CANDIDA – ASSOCIATED LESIONS I. DENTURE STOMATITIS Most prevalent site is palatal mucosa Classified into three different types Type I – Localized to minor erythematous sites Type II – affects a major part of the denture covered mucosa Type III – has a granular mucosa

17. II. ANGULAR CHEILITIS Characterized by erythema, fissuring, scaling Saliva tends to pool in, keeping the area moist & favoring yeast infection Candidal infection involving perioral skin - creates a clinical pattern CHEILOCANDIDIASIS

18. CHEILOCANDIDIASIS A diffuse form of chronic candidiasis characterized by pain , swelling, erythema with focal ulcerations, and crusting is called cheilocandidiasis . It represents a secondary candidal infection superimposed on areas of trauma from mechanical or solar factors .

19. Cheilocandidiasis and juvenile juxtavermilion candidiasis refer to more extensive and often desquamative lesions affecting the full width of the lip, even extending into adjacent lesions. They are associated with habitual lip sucking, prolonged dental appointments, sunlight, and chronic candida infection. Differential diagnoses of these lesion include perioral erythema and Id reaction (localized sterile vesiculopapular rash ).

20. Etiology Shafer, Hine, Levy. Textbook of Oral Pathology, 6th edn;2009.

21. III. MEDIAN RHOMBOID GLOSSITIS Characterized by a erythematous lesion in the centre of the posterior part of the dorsum of the tongue. Lesion has a oval configuration Resulting from atrophy of the filiform papillae and lobulated. Smokers, denture-wearers and patients using inhalation steroids have an increased risk Asymptomatic Management is restricted to a reduction in predisposing factors.

22. III. MEDIAN RHOMBOID GLOSSITIS Brocq : 1914 Prevalence: < 1% Males > Females

23. Synonyms Median candidiasis of the tongue Atypical/ paramedial rhomboid glossitis Central papillary atrophy Posterior lingual papillary atrophy Posterior midline atrophic candidiasis

24. Etiology Embryological Inflammatory Immunological Infectious Associated with: Tobacco smoking Denture wearing Trauma Int J Oral Surg 1984;13(5):411-415. Oral Surg Oral Med Oral Pathol 1996;81(4):379-80.

25. Med Oral Patol Oral Cir Bucal 2005;10:123-7.

26. Kissing lesion

27. Investigations Cytosmear Fungal culture Biopsy: Candidal hyphae > 85% of lesions

28. Management of median rhomboid glossitis Topical antifungal: clotrimazole troches fluconazole Topical corticosteroid: fluocinonide 0.05% clobetasol 0.05 % Bruch JM, Treister NS. Clinical Oral Medicine and Pathology.

29. SECONDARY ORAL CANDIDIASIS Accompanied by systemic mucocutaneous candidiasis and other immune deficiencies Chronic mucocutaneous candidiasis Also affect the skin, the nail bed, genital mucosa Face and scalp may be involved Occur as part of Endocrine disorders – Hyperparathyroidism and Addisons disease Myeloperoxidase deficiency Chediak – Higashi syndrome, Severe combined immunodeficiency syndrome characterized by a defect in the function of the cell-mediated immunity Thymoma is a neoplasm of thymic epithelial cells Chronic familial mucocutaneous candidiasis an inherited disorder, occurs early in life.

30. ORAL CANDIDIASIS ASSOCIATED WITH HIV 90% of AIDS patients have oral candidiasis Most common types Pseudomembranous candidiasis Erythematous Candidiasis Angular cheilitis and Chronic hyperplastic candidiasis

31. DIAGNOSIS AND LABORATORY FINDINGS Smear :- useful in Pseudomembranous oral candidiasis and angular cheilitis Swab :- Taken by rubbing cotton-tipped swabs over the lesional tissue. Imprint Culture : Sterile (plastic) foam pads submerged in sabouraud broth placed on the infected surface for 60 seconds. Cultivated at 37 o C. Result is expressed as colony forming units per cubicmillimeter . ( CFU/mm 3 ) Valuable in erythematous candidiasis and denture stomatitis . Salivary culture technique :- Used to get an adequate quantification of candida. Histopathological Examination :- Chronic plaque-type and nodular candidiasis, identify the presence of epithelial dysplasia.

32. Treatment of Denture stomatitis Eliminate predisposing factors Improve denture hygiene Denture should be stored in antimicrobial solutions Type III denture stomatitis treated with surgical excision

33. Treatment of Angular cheilitis Topical treatment with miconazole A mild steroid ointment suppress the inflammation A moisturizing cream prevent new fissure formation

34. Treatment of Median rhomboid glossitis Topical antifungal: clotrimazole troches fluconazole Topical corticosteroid: fluocinonide 0.05% clobetasol 0.05 % Bruch JM, Treister NS. Clinical Oral Medicine and Pathology.

35. ANTIFUNGALS Topical antifungals are usually the drug of choice for uncomplicated, localized candidiasis in patients with normal immune function. Systemic antifungals are usually indicated in cases of disseminated disease and/or in immunocompromised patients .

36. Dosage form/ strength Indication Miconazole cream 2% Angular cheilitis Clotrimazole cream 1% Angular cheilitis Ketoconazole cream 2% (Prescription) Angular cheilitis Nystatin ointment 100,000 units/gram (Prescription) Angular cheilitis Nystatin topical powder 100,000 units/gram (Prescription) Denture stomatitis Nystatin oral suspension 100,000 units/gram (Prescription) Intraoral candidiasis   Betamethasone dipropionate clotrimazole cream (Prescription) Chronic angular cheilitis Clotrimazole troches 10 mg (Prescription) Intraoral candidiasis Amphotericin B 100 mg/ml (Prescription)   Intraoral candidiasis

37. Generic name   Formulation Amphotericin B 100 mg/ml oral suspension Clotrimazole 10 mg troche Fluconazole 100 mg tablet 10 mg/ml oral suspension 40 mg/ml oral suspension Itraconazole   100 mg capsule 10 mg/ml oral suspension Ketoconazole 200 mg tablet Nystatin 100,000 units/ml oral suspension 200,000 units/ml pastille 500,000 units/ml tablet 100,000 units/ml vaginal tablet

38. ANTIFUNGALS Medication should be continued for at least 48 hours after the disappearance of clinical signs of candidiasis along with complete healing and the absence of mucosal erythema. Some sources recommend drug therapy should be continued for 10–14 days regardless of the disappearance of clinical signs of candidiasis .

39. SURGERY May be advised for hyperplastic and nodular types of candidiasis. (Cryotherapy , CO2 laser therapy, and cold-knife surgery). Small lesions may be allowed for primary healing Large lesions are closed by skin grafts after surgery. But there are chances of reccurrence . Long term and intermittent anti fungal therapy may lead to complete or partial resolution.

40. Prognosis Prognosis is good if predisposing factors are reduced or eliminated. Persistant chronic plaque-type and nodular candidiasis increased risk for malignant transformation. Patients with severe immunosuppression may encounter disseminating candidiasis with a fatal course.

41. HAIRY LEUKOPLAKIA Oral hairy Leukoplakia is a corrugated white lesion that usually occurs on the lateral or ventral surfaces of the tongue in patients with severe immunodeficiency Second most common HIV associated lesion Marker of disease activity associated with low CD4 + T-lymphocyte counts. Not pathognomonic for HIV since other immunodeficiencies , such as immunosuppressive drugs and cancer chemotherapy are also associated with HL. Also occur in patients undergoing prolonged steroid theropy . It was first reported by Greenspan and coworkers in 1984 in young homosexual males.

42. Epidemiology: Prevalence may be as high as 80% The prevalence in children is lower 2% More frequently encountered in men Correlation between smoking and HL has also been observed. Etiology and Pathogenesis: 1) Strongly associated with Epstein- Barrvirus with low levels of CD4 + T-lymphocytes 2) Antiviral medication, which prevents EBV replication, support the fact that EBV is an etiological factor.

43. Clinical Findings: Most commonly involves the lateral border of the tongue but may extend to the ventral or dorsal surfaces. Occasionally located on the buccal mucosa. Typical clinical appearance is vertical white folds oriented as a palisade along the borders of the tongue Lesions on the tongue are corrugated and have a shaggy or frayed appearance May also be displayed as white and somewhat elevated plaque, which cannot be scraped off It is often bilateral. Asymptomatic

44. Diagnosis: Diagnosis of HL based on clinical characteristics, a histopathologic examination and detection of EBV

45. Pathology : Histopathology of HL is characterized by a) Severe hyperkeratosis with an irregular surface b) Acanthosis with superficial edema c) corrugations and often thin tufts (“hairs”) may be seen projecting from the surface d) numerous koilocytic cells (virally affected “balloon” cells) in the spinous layer. e) Pyknotic nuclei

46. 2) Characteristic microscopic feature is homogenous viral nuclear inclusions with a residual rim of normal chromatin 3) Candida hyphae surrounded by polymorphonuclear granulocytes - common feature. 4) EBV can be detected by in-situ hybridization or by immunohistochemistry.

47. Differential Diagnosis It is important to differentiate HL from other clinically similar entities such as Hyperplastic candidiasis Idiopathic leukoplakia Leukoplakia induced by tongue chewing Tobacco associated leukoplakia Lichen planus Lupus Erythematosus White sponge nevus Verrucous Leukoplakia

48. Treatment and Prognosis No treatment is indicated Condition disappears when antiviral medications such as zidovudine , acyclovir, or ganacyclovir are used in the treatment of the HIV infection Topical application of podophyllin resin 25% solution (or) tretinoin short-term resolution of the lesions. HL is not related to increased risk of malignant transformation.

49. PREMALIGNANT LESIONS LEUKOPLAKIA ERYTHROPLAKIA OSMF

50. ORAL LEUKOPLAKIA A Keratotic plaque occurring on mucous membranes considered a premalignant lesion. Definition: WHO defined leukoplakia as “a white patch or plaque that cannot be characterised clinically or pathologically as any other disease” Oral leukoplakia is defined as a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion.

51. Etiology and Pathogenesis: Etiologic factors of Leukoplakia Tobacco products Ethanol Hot, Cold, Spicy and acidic foods and beverages Alcoholic mouth rinse Occlusal trauma Sharp edges of prostheses or teeth Actinic radiation Syphilis Presence of candida albicans Presence of viruses Leukoplakia commences as a protective reaction against a chronic irritant.

52. Epidemiology: Prevalence is 2.6% Over 50yrs of age In men Clinical Findings: Asymptomatic L ip vermilion, buccal mucosa, mandibular gingiva, tongue, floor of the mouth, hard palate, maxillary gingiva, Lip mucosa and soft palate. Borders may be distinct or indistinct, smoothly contoured or ragged. Solitary or multiple plaques scattered through the mouth Floor of the mouth and the lateral borders of the tongue are high-risk sites for malignant transformation

53. 6. It is divided into a. Homogenous type and b. Non-Homogenous type 7. Classification: Homogenous Leukoplakia White, well-demarcated plaque with an identical reaction pattern throughout the entire lesion. No red component A smooth thin surface to a leathery appearance with surface fissures as cracked mud. Asymptomatic

54. 2. Speckled Leukoplakia: Composed of white and red flecks of fine or coarse variety.

55. 3. Erythroleukoplakia : Combination of red and white patches, segregation of the red and white components.

56. 4. Verrucous leukoplakia:- Large white verrucous areas to small nodular structures. Verrucous , papillary (nodular) or exophytic components More aggressive proliferation pattern, recurrence rate are designated proliferative verrucous leukoplakia (PVL) PVL common in women lower gingiva is a predilection site. Malignant potential is high in PVL.

57. Diagnosis: The cause, such as a sharp tooth cusp or restoration, should be eliminated. If healing does not occur in 2 weeks, biopsy is essential. Pathology: Hyperkeratosis without any other features is compatible with homogenous oral leukoplakia. Histological features include hyperkeratosis, atrophy, hyperplasia with or without dysplasia. Carcinoma-in-situ or intraepithelial carcinoma Invasive squamous cell carcinoma

58. Leukoplakia may also be divided Reversible leukoplakia Irreversible leukoplakia Malignant potential: Ranges between 3% and 7%. Lesions in the floor of the mouth, ventral surface of the tongue, margins of the tongue and retromolar region have a higher risk.

59. High-Risk Leukoplakias Red component Raised component Presence in high-risk oval Tobacco and alcohol use Non smoker and un known etiology Non reversible type Microscopic atypia

60. Differential Diagnosis: The keratotic varieties considered in the differential diagnosis are Lichen planus Leukoedema Cheek-biting lesion Smokeless tobacco lesion Lupus erythematosus Hyperplastic or hypertrophic candidiasis Hairy leukoplakia Electrogalvanic or mercury contact allergy Verrucous or squamous cell carcinoma Verruca vulgaris White sponge nevus.

61. Management of Leukoplakia: Discontinue the habits Cold-knife surgical excision, laser surgery , widely used to eradicate leukoplakias Low-risk lesions – identify and eliminate the local and chronic causative irritants Chemoprevention in the form of topical bleomycin Systemically administered antioxidants such as retinoic acid, β carotene, and vitamins C & E have been administered Lesions are large and widespread – stripping procedures with free grafts. Reexamine every 3 months for the first year. Following 5 years of no relapse, self examination.

62. Recurrence after surgical treatment 10%–35% of cases. Nonsurgical advantages . Minimal adverse effects to patients Large area of the oral mucosa Patients with medical problems due to surgical risks. Easy application Relative low cost. 91

63. Carotenoids 1.Beta-Carotene Group of extremely hydrophobic molecules with little or no solubility in water. Betacarotene is a vitamin A precursor. Found in Dark green, orange or yellowish vegetables, such as spinach, carrots , sweet potato, mango, papaya, and oranges. 92 A Review of the Nonsurgical Treatment of Oral Leukoplakia International Journal of Dentistry 2010

64. Lycopene This is a fat-soluble red pigment F ruit vegetables ( tomatoes). Most efficient biological antioxidizing agent. Antioxidant It binds to chemical species that react with oxygen. Modify intercellular exchange junctions . This is considered to be an anticancer mechanism Lycopene inhibits human neoplastic cellular growth by interfering with growth factor receptor signaling. 93 A Review of the Nonsurgical Treatment of Oral Leukoplakia International Journal of Dentistry 2010

65. Vitamins L-Ascorbic Acid (Vitamin C). Citrous fruits as kiwi , strawberries , papaya, and mango. The current US recommanded dose is 100–120 mg/per day for adults. 140 mg/day smokers because they have low concentration of L-AA in serum leukocytes. 94 A Review of the Nonsurgical Treatment of Oral Leukoplakia International Journal of Dentistry 2010

66. α- Tocoferol (Vitamin E) α- Tocoferol (AT) is most active form of vitamin E. Plant oil, margarine, and green leaves. The recommended dose is 10 mg/day men 8 mg/day women. Absorption rate is reduced consumption exceeds 30mg/day. α- Tocoferol is an effective antioxidant at high levels of oxygen. Protects cell membrane from lipidic peroxidation . 95 A Review of the Nonsurgical Treatment of Oral Leukoplakia International Journal of Dentistry 2010

67. Retinoic Acid (Vitamin A) Retinoic acid is obtained from carotene and animal products such as meat, milk, and eggs. In the intestine retinoic acid is converted into retinal and retinol. Retinoids are transported by plasma proteins. Hepatic metabolization cytochrome P- 450. Hypervitaminosis  consumption exceeds storage capacity of liver 13-cRA was used for the first time against acne in 1969. 96 A Review of the Nonsurgical Treatment of Oral Leukoplakia International Journal of Dentistry 2010

68. Retinoids affect Keratin production Expression of growth factors and kinases Oncogenesis Apoptosis Production of the collagen matrix Immunologic and inflammatory response Cellular differentiation Embrionary morphogenesis and Carcinogenesis 97 A Review of the Nonsurgical Treatment of Oral Leukoplakia International Journal of Dentistry 2010

69. Fenretinide Fenretinide (4-HPR) or N-(4-hydroxyphenyl retinamide ) is a vitamin A analogue. Synthesized in United States 1960. Less toxic than many other vitamin A analogues. 98 A Review of the Nonsurgical Treatment of Oral Leukoplakia International Journal of Dentistry 2010

70. Photodynamic Therapy (PDT) is a noninvasive method for the treatment of premalignant lesions and head and neck Cancers photosensitising drug ( photosensitiser ), oxygen, and visible light 99 A Review of the Nonsurgical Treatment of Oral Leukoplakia International Journal of Dentistry 2010

71. ERYTHROPLAKIA Pre-malignant lesion Prevalence: 0.02 – 0.83% India: 0.2% Female: male = 1:1.04 Well-demarcated, fiery red patch

72. The word is an adaptation of the French term “ erythroplasie de Queyrat ” , which was originally used by Queyrat to describe a precancerous red lesion that develops on the glans penis . Oral erythroplakia is clinically and histopathologically similar to the genital process with a comparable premalignant tendency.. Oral Oncol 2005;41:551-61.

73. Definitions WHO 1978 Bright red velvety plaques which cannot be characterized clinically or pathologically as being due to any other condition. Axell et al 1984 Lesions of the oral mucosa that present as bright red patches or plaques that cannot be characterized clinically or pathologically as any other condition. Axell et al 1986 Lesions of the oral mucosa that present as red areas and cannot be diagnosed as any other definable lesion. Pindborg et al 1997 (WHO) A fiery red patch that cannot be characterized clinically or pathologically as any other definable lesion. Crit Rev Oral Biol Med 2003;14(1):47-62.

74. Provisional diagnosis A provisional diagnosis of oral erythroplakia is made when a lesion at clinical examination cannot be clearly diagnosed as any other disease of the oral mucosa with red appearance. Definitive diagnosis A definitive diagnosis of oral erythroplakia is made as a result of identification, and if possible elimination, of suspected etiological factors and, in the case of persistent lesions, histopathological examination. J Oral Pathol Med 1996;25:49-54.

75. Etiology and Pathogenesis : Etiology is uncertain, most cases are associated with heavy smoking. Majority of erythroplakias exhibit premalignant and malignant changes. EP is often regraded as the earliest sign of asymptomatic oral cancer. EP’s reddish color results from the absence of a surface keratin layer, connective tissue papillae project close to the surface, general failure of the epithelial cells to achieve significant maturation (keratinization)

76. Appears as a velvety red or granular red macule (patch) that may be slightly raised. Occurs predominantly in older men, in the 6 th and 7 th decades of life. More commonly seen on the floor of the mouth, the ventral tongue, the soft palate, and the tonsillar fauces , all prime areas for the development of carcinoma Multiple lesions may be present. Clinical features

77. 5) Commonly described as erythematous plaques with a soft velvety texture. 6) Asymptomatic 7) This painless lesion varies greatly in size, and borders may be well circumscribed or may blend imperceptibly with the surrounding normal mucosa. 8) Three different clinical appearances described by shear. a) the homogenous form, red in appearance b) patches of Erythroplakia and leukoplakia c) Speckled erythroplakia or granular erythroplakia

78. 9) Homogenous EP is generally much more aggressive than leukoplakia or speckled EP 10) The floor of the mouth is the most common site in men, mandibular gingival-alveolar mucosa – mandibular sulcus is most common site in women. 11) Retromolar region is the second most common site in both genders.

79. Most asymptomatic malignant erythroplakic lesions are small; 84% are ≤ 2 cm in diameter, and 42% are ≤ 1 cm. Burket’s Oral Medicine – 11 th edn.

80. Diagnosis: The provisional diagnosis is based on the clinical observation of a white or red patch. If trauma is suspected, sharp tooth cusp or restoration, should be eliminated. If healing doesn’t occur in 2 weeks, biopsy is essential. Histopathology: 80 to 90% of cases of erythroplakia are histopathologically show severe epithelial dysplasia, carcinoma-in-situ or invasive carcinoma Epithelial dysplasia is defined as a precancerous lesion of stratified squamous epithelium charaterized by cellular atypia and loss of normal maturation. Carcinoma in situ is defined as a lesion in which the full thickness of squamous epithelium shows the cellular features of carcinoma without stromal invasion

81. Criteria used for Diagnosing Epithelial Dysplasia

82. Differential Diagnosis: The lesions to be considered in the differential diagnosis of Erythroplakia are: Traumatic erythema Atrophic candidiasis Purpuric macule (early stage) Macular hemangioma Contact allergy Other infection Localized gingivitis Kaposis sarcoma (early stage)

83. Treatment and Prognosis: If a red lesion persists for more than 14 days biopsy is mandatory Epithelial dysplasia or carcinoma in situ warrants complete removal of the lesion Alcohol and smoking are well established risk factors - advice the patients to discontinue the habits. 4) Cold knife surgical excision, as well as laser surgery widely used to eradicate erythroplakias 5) Follow-up of Erythroplakia :- Reexamine the premalignant site irrespective of surgical excision every 3 months for the first year. Follow-up intervals may be extended to once every 6 months.

84. Management of oral Leukoplakia / Erythroplakia Adapted from vander waal et al

85. ORAL SUBMUCOUS FIBROSIS Chronic insidious disease caused by arecanut use, and is associated with both significant morbidity and an increased risk for malignancy. History: First described by schwartz in 1952 coined the term “ atrophia idiopathica ( trophica ) mucosae oris ” In 1953, Joshi from Mumbai redesignated the condition as oral submucous fibrosis.

86. Etiology and Pathogenesis: Arecoline a primary etiologic factor. Arecoline affecting the metabolism of collagen leads to an increased fibrosis. Evidence of a genetic predisposition.

87. Clinical Features: EARLY OSF (Prodromal Symptoms) Burning sensation in the mouth Ulcerations or generalized inflammation Excessive salivation Defective gustatory sensation Dryness of the mouth Appearance of small vesicles in the cheek and palate. Petechiae on the tongue, labial and buccal mucosa Pain where submucous fibrotic bands are developing

88. ADVANCED OSF : White marbling Fibrous bands appear beneath an atrophic epithelium In the buccal mucosa run in a vertical direction Circular band around the entire rima oris (mouth orifice) Impairment of tongue movement Difficulty in opening the mouth Inability to whistle or blow out a candle Difficulty in swallowing Increased fibrosis interferes with speech 25% patients exhibit oral leukoplakias .

89. Diagnosis: For the diagnosis of OSF a. Palpable fibrous bands b. Mucosal texture feels tough and leathery c. Blanching of mucosa d. Histo pathological features atrophic epithelium loss of rete ridges and juxta epithelial hyalinization of laminapropria

90. Pathology: Histo pathologic features of OSF are Fine fibrils of collagen Edema Hypertrophic fibroblasts Dilated and congested blood vessels Infiltration of neutrophilic and eosinophilic granulocytes Down-regulation of fibroblasts Epithelial atrophy Loss of rete pegs Early signs of hyalinization Epithelial dysplasia appears in 7-26% of OSF tissues.

91. Management: Elimination of the habit Management strategies are Nutritional support: high protein and calories, vitamin B complex and minerals Immunomodulatory drugs: Local and systemic application of glucocorticoids and placental extract Glucocorticoids act as immunosuppressive agents. Also prevent or suppress inflammatory reactions.

92. Physiotherapy: 1. Heat has been commonly used. In the form of hot rinses, lukewarm water, or short wave and microwave diathermy. 2. Microwave diathermy seems superior to short wave. Local Drug Delivery Local injections of dexamethasone, hyaluronidase and placental extract

93. 2 . Hyaluronidase Breaks down hyaluronic acid Lowers the viscosity of the intercellular cement substances Decreases collagen formation 3. Chymotrypsin , acts as a proteolytic and anti inflammatory agent.

94. Placental extracts: Local injections as well as parental form Placenta acts as a biogenous stimulator Other actions of placental extract are Anti-inflammatory Increase in blood circulation Arrest of tissue growth stagnation, metabolic degenerative conditions and lowered immunity response Used as a local nutrient.

95. Combined Therapy : Local injections of chymotrypsin, hyaluronidase and dexamethasone Combined therapy with nylidrin hydrochloride, vitamins D, E and B complex, iodine, placental extract, local and systemic corticosteroids and physiotherapy - success rate of 62% in OSMF

96. Surgical Management: Submucosal resection of fibrotic bands and replacement with a partial-thickness skin or mucosal graft Bilateral temporalis myotomy New treatment regimen composed of surgical excision of the fibrotic bands with submucosal placement of fresh human placental grafts, followed by local injections of dexamethasone for advanced cases .

97. IMMUNOPATHOLOGIC DISEASES ORAL LICHENPLANUS DRUG INDUCED LICHENOID REACTION LICHENOID REACTION OF GVHD LUPUS ERYTHEMATOSIS

98. ORAL LICHEN PLANUS INTRODUCTION: Chronic inflammatory disease that affects the skin and the mucous membrane. First described by Erasmus wilson in 1869. One of the most common oral diseases. The exact cause is unknown, but the immunologic system plays a leading role in the pathogenesis.

99. Oral Lichenoid reactions include the following disorders: Lichen planus Lichenoid contact reactions Lichenoid drug eruptions Lichenoid reactions of graft-versus-host disease (GVHD)

100. Etiology and Pathogenesis Is not known Immune system has a primary role supported by the subepithelial band formed infiltrate dominated by T-lymphocytes and macrophages and the degeneration of basal cells known as liquefaction degeneration. Autoreactive T-lymphocytes may be of primary importance for the development of oral lichen planus . Epidemiology: Prevalence is 0.5 – 2.2% Commonly seen in women than men. Mean age at the time of diagnosis is approximately 55 years.

101. Lavanya N, Jayanthi P, Rao UK, Ranganathan K . Oral lichen planus : An update on pathogenesis and treatment. J Oral Maxillofac Pathol 2011;15:127-32.

102. Clinical Findings: Cutaneous lesions encountered in 15% of patients with OLP. Classic appearance of skin lesions consists of pruritic erythematous to violaceous papules which are flat topped, small, angular only a few millimeters in diameter. Larger plaques, covered by a fine, glistening scale. Surface is covered by characteristic, very fine grayish-white lines, called wickham’s striae Occur in a bilaterally symmetrical pattern, on the flexor surfaces of the wrist and forearms, the inner aspect of the knees and thighs, and the trunk.

103. Primary symptom is a severe pruritis Trauma may aggravate the disease, referred to as a K oebner phenomenon. Most frequent extra oral mucosal site is the genital mucosa. Classic skin lesions described as P urplish P olygonal P lanar P ruritic P apules P laques

104. Oral Manifestations: Classically characterized by lesion consisting of radiating white or gray, velvety, thread – like papules in a linear, annular, or retiform arrangement A tiny white elevated dot present at the intersection of the white lines, known as the striae of wickham . OLP may contain both red and white components with different textures. Reticulum Papules Plaque-like Bullous Erythematous Ulcerative

105. Reticular form: Characterized by fine, white lines or striae Striae form a network also show annular (circular) patterns. A peripheral erythematous zone Most frequently observed bilaterally in the buccal mucosa.

106. Papular form: Present in the initial phase of the disease. Characterized by small white dots

107. Plaque form: Homogeneous well-demarcated white plaque, surrounded by striae . Similar to homogeneous oral leukoplakias Most often encountered in smokers

108. D) Bullous form: Unusual Clinically resemble erosive lichen planus

109. E) Erythematous (Atrophic) OLP: Characterized by homogeneous red area Present in the buccal mucosa or palate, striae are frequently seen in the periphery Exclusively affecting attached gingiva presents as desquamative gingivitis.

110. F ) Ulcerative form: Disabling form of OLP Fibrin-coated ulcers are surrounded by an erythematous zone frequently displaying radiating white striae Complains of a smarting sensation

111. Diagnosis Lichenoid contact reactions most often detected on the buccal mucosa and lateral border of the tongue. Oral Lichenoid drug eruptions - Patient’s drug history - Withdrawal of the drug causes resolution of the lesions Oral Graft Versus Host Disease - Lesion is usually generalized in GVHD - Frequently seen simultaneously with xerostomia , presence of localized skin involvement and liver dysfunction

112. Discoid Lupus Erythematosus - Striae in DLE are typically more prominent with a more marked hyperkeratinization may terminate against a sharp demarcation. Leukoplakia - Leukoplakia is not featured with papular or reticular elements. Mucous membrane pemphigoid - In pemphigoid lesions, the epithelium is easily detached from the connective tissue by a probe ( Nikolsky’s phenomenon) Erythema Multiforme - In EM, the lesions do not typically appear with reticular or papular elements.

113. Pathology Histopathologic features Areas of hyper para keratosis or hyper ortho keratosis Thickening of the granular cell layer Saw-toothed appearance to retepegs “Liquefaction degeneration” or necrosis of the basal cell layer. An eosinophilic band may be seen just beneath the basement membrane and represent fibrin covering the lamina propria . A dense subepithelial band-shaped infiltrate of lymphocytes and macrophages is also characteristic of the disease .

114. MANAGEMENT OF ORAL LICHEN PLANUS I PHARMACOLOGICAL MODALITIES CORTICOSTEROIDS Ability to modulate inflammation and immune response Topical midpotency corticosteroids triamcinolone acetonide , high-potency fluorinated corticosteroids fluocinonide acetonide , betamethasone and superpotent corticosteroids clobetasol are used Wide spread forms of OLP - potent and superpotent corticosteroids mouth washes and intralesional injections. Antifungal therapy Systemic corticosteroids for recalcitrant erosive or erythematous LP Systemic prednisolone (40-80mg for 5-7 days)

115. B. CALCINEURIN INHIBITORS Calcineurin is inhibited by Cyclosporine, tacrolimus and pimecrolimus . Cyclosporine An immunosuppressant used widely in post- allogenic organ transplant. Used as a mouthrinse or topically with adhesive bases in OLP Expensive Reserved for highly recalcitrant cases of OLP Causes gingival hyperplasia

116. 2. TACROLIMUS: Immunosuppressive agent for the treatment of atopic dermatitis Successfully used in recalcitrant OLP cases Has a potential cancer risk from the prolonged use Recommended for short periods. 3. PIMECROLIMUS: 1% topical cream used for OLP Has significant anti-inflammatory and immunomodulatory capabilities.

117. C. RETINOIDS Topical retionoids - tretinoin , isotretinoin and fenretinide Has immunomodulatory properties and effective in OLP Reversal of white striae Systemic retinoids used in severe lichen planus . D. DAPSONE Antibacterial agent Used in the treatment of leprosy Used for skin diseases (acts as an anti inflammatory agent) Common untoward effect is hemolysis.

118. E) MYCOPHENOLATES Used to treat psoriasis Mycophenolate mofetil is a immunosuppressive drug used in organ transplant To treat severe cases of OLP Expensive F) LOW-DOSE, LOW MOLECULAR WEIGHT HEPARIN (ENOXAPARIN) Devoid of anticoagulant properties inhibits T-lymphocyte heparanase activity Simple, effective and safe treatment for OLP Injected subcutaneously has no side effects.

119. G. EFALIZUMAB Is a recombinant humanized monoclonal antibody An immunosuppressant in the treatment of psoriasis Causes improvement in OLP Once a week as a subcutaneous injection.

120. II NON-PHARMACOLOGICAL MODALITIES PUVA THERAPY: Uses photochemotherapy with 8-methoxypsoralen and long wave ultraviolet light (PUVA) Methoxypsoralen is given orally, followed by administration of 2 hours of UV radiation intraorally in the affected sites. Successfully used in the treatment of severe cases of OLP. B. PHOTODYNAMIC THERAPY Uses a photosensitizing compound like methylene blue. It may reverse the hyper proliferation and inflammation of lichen planus .

121. C. LASER THERAPY: Surgical management using cryosurgery and different types of lasers have been tried. All types of laser destroy the superficial epithelium containing the target keratinocytes by protein denaturation. Effectiveness is yet to be proven.

122. Lavanya N, Jayanthi P, Rao UK, Ranganathan K . Oral lichen planus : An update on pathogenesis and treatment. J Oral Maxillofac Pathol 2011;15:127-32.

123. DRUG-INDUCED LICHENOID REACTIONS Lichenoid reactions and Lichen planus exhibit similar histopathologic features. Lichenoid reactions were differentiated from Lichen planus on the basis of The administration of a drug, contact with a metal, use of a food flavoring or systemic disease Resolution when the drug or other factor was eliminated Clinically , lichenoid reactions may exhibit the classic appearance of lichen planus , but atypical presentations are seen. LICHENOID REACTIONS

124. DRUG-INDUCED LICHENOID REACTIONS Clinically , there is often little to distinguish drug-induced lichenoid reactions from lichen planus . Lichenoid lesions that include the lip, symmetric in distribution and also involve skin are more likely to be drug-related. Histopathologically , Lichenoid drug eruptions may show a deep as well as superficial perivascular lymphocytic infiltrate rather than the classic band like infiltrate of lichenplanus . Drug-induced Lichenoid reactions may resolve promptly when the offending drug is eliminated.

125. Important causes of lichenoid reactions Gold therapy N onsteroidal anti-inflammatory drugs (NSAIDS), D iuretics O ther antihypertensives O ral hypoglycemic agents of the sulfonyl urea

126. Drugs and Materials implicated in Oral Lichenoid reactions Category Drugs or Materials Antimicrobials Dapsone Ketoconazole Para- aminosalicylic acid Sodium amino salicylate Streptomycin Sulfamethaxazole Tetracycline Antiparasitics Antimony compounds ( stibophen , stibocaptate ) Organic arsenicals Chloroquine Pyrimethamine Quinacrine Anti hypertensives ACE inhibitors Chlorothiazide Hydrochlorothiazide Labetalol Mecurial Diuretics Methyldopa Practolol

127. Antiarthritics Aurothioglucose Colloidal gold (Europe only) Gold sodium thiomalate , thiosulfate Anxiolytics Lorazepam NSAIDS Fenclofenac Ibuprofen Naproxen Phenylbutazene Oral hypoglycemic agents Chlorpropamide Tolazamide Tolbutamide Uricosuric agents Allopurinol Miscellaneous drugs Iodides Pencillamine Quinidine Sulfate Chemicals, dental restorative materials Substituted Paraphenylene-diamines used in color film developers, dental casting alloys and amalgam restorations

128. Etiology and Pathogenesis: Drugs and their metabolites act as haptens trigger a lichenoid reaction Pencillin and gold may bind directly to self- protiens , presented by antigen-presenting cells and perceived as foreign by specific T-lymphocytes, similar to a delayed hypersensitivity reaction. DILRs may result from poor drug metabolism

129. Clinical Findings: - Unilateral Ulcerative reaction pattern Oral lichen planus and lichenoid reactions should be considered , clinically indistinguishable. Lichenoid drug eruptions appear similar to Lichen ruber planus and may be severely pruritic .

130. Diagnosis: Oral lesions comprise a white reticulum (or) papules concurrently with erythematous and ulcerative lesions A correct diagnosis is easier when a patient develops DILR after starting a new drug. Management: Discontinuance of the drug and symptomatic treatment with topical steroids.

131. LICHENOID REACTIONS OF GRAFT VERSUS HOST DISEASE Complex multisystem immunologic phenomenon characterized by the interaction of immunocompetent cells from one individual (the donor) to a host (the recipient Etiology and Pathogenesis: Major cause is allogenic hematopoietic cell transplantation

132. Clinical Findings: Occur in both acute and chronic GVHD Lesions of GVHD are indistinguishable from the lesions of OLP. The lesions of GVHD associated with a more widespread involvement of the oral mucosa Involves the cheeks, tongue, lips and gingivae A fine reticular network of white striae that resembles OLP is seen Complain of a burning sensation of the oral mucosa. Xerostemia

133. Clinical Manifestations Skin lesions present with pruritic maculopapular and mobiliform rash, affecting the palms and soles Violaceous scaly papules and plaques, generalized erythroderma , bulla formation. A toxic epidermal necrolysis like epidermal desquamation may occur .

134. Diagnosis : Presence of systemic GVHD facilitates the diagnosis of oral mucosal changes of chronic oral GVHD Differential Diagnosis: The differential diagnosis of GVHD includes Candidiasis Toxic reactions to chemotherapeutic drugs Unusual viral infections (herpes virus, cytomegalovirus) Lichenoid drug eruptions

135. Management: Same as that of OLP, topical steroid preparations, fluocinonide and clobetasol gel. Patients with a history of oral GHVD should be examined for oral malignancies as part of the medical follow-up procedure.

136. ALLERGIC REACTIONS Lichenoid contact reactions Reactions to dentifrice and chlorhexidine

137. LICHENOID CONTACT REACTIONS Delayed hyper sensitivity reaction to constituents derived from dental materials likes mercury (Hg) Clinical Findings: Delayed hypersensitivity reaction to amalgam fillings. Same reaction patterns as seen in OLP Major clinical difference between OLP and LCR is the extensions of lesions Non symptomatic

138. Diagnosis: Replacement of the dental material may assist to discriminate between LCR and OLP. Management: Replacement of dental materials result in cure in 90% of the cases Lesions expected to heal within 1 to 2 months.

139. B. REACTIONS TO DENTIFRICE AND CHLORHEXIDINE Rare Allergic reactions include flavor additives such as carvone and cinnamon or preservatives Clinical manifestations – fiery red edematous gingiva, include both ulcerations and white lesions Involve other sites labial, buccal and tongue mucosa. Healing seen after withdrawal of the allergen – containing agent.

140. TOXIC REACTIONS Reactions to smokeless tobacco Smoker’s palate

141. A. Reactions to Smokeless Tobacco Smokeless tobacco divided into three different groups; chewing tobacco, moist snuff and dry snuff. Mildest form, the lesion noted as wrinkles at the site of application, high consumers may display a white and leathery lesion. Gingival retractions most common adverse reaction seen in smokeless tobacco habit. Smokeless tobacco products contain nitrosamines polycyclic hydrocarbons, aldehydes, heavy metals, and polonium 210

142. B. SMOKER’S PALATE Dark brown pigmentations of the oral mucosa and as white leathered lesions of the palate. Red dots can be observed representing orifices of accessory salivary glands. More prevalent in men Common in high consumers of pipe tobacco, cigarettes and Reverse smoking Etiology related to the high temperature.

143. REACTIONS TO MECHANICAL TRAUMA MORSICATIO FRICTIONAL KERATOSIS

144. A. MORSICATIO Habitual chewing Seen in the buccal and lip mucosa Three times more common in women Management is by assurance

145. FRICTIONAL KERATOSIS Characterized by a white lesion without any red elements Obesrved in areas subjected to increased friction

146. Etiology and Pathogenesis: Increased abrasion stimulates the epithelium to respond with an increased production of keratin. Regarded as a physiologic response to trauma Predisposing factors are smoking and alcohol Clinical Findings: Seen in edentulous areas of the alveolar ridge Asymptomatic Management: No surgical intervention Reduce predisposing factors.

147. OTHER RED AND WHITE LESIONS Benign Migratory Glossitis (Geographic Tongue) Leukoedema White sponge Nevus Hairy tongue

148. A. GEOGRAPHIC STOMATITIS 1831 – Rayer 1955 – Cooke : “erythema migrans ” Prevalence : 1 – 2.5% Age : 20-29 years Females > Males Hacettepe Diş Hekimliği Fakültesi Dergisi 2008;32(2):73-8. Pediatr Dentistry 1992;14(6):392-6.

149. Benign inflammatory condition of the mucosa with map-like areas of erythema which are not constant in size, shape or location. Oral Surg Oral Med Oral Pathol 1993;76(4):476-9.

150. Synonyms Erythema migrans Erythema circinata migrans Benign migratory glossitis Stomatitis areata migrans Annulus migrans Cooke’s disease Continental tongue M arginal exfoliative glossitis Transitory benign plaques of the tongue Wandering rash of the tongue Exfoliatio areata linguae Lingua geographica Am J Med 2002;113:751-5.

151. Etiopathogenesis Genetic (B15 , DR7, DRW6 and CW6) Nutritional deficiency Psychological disturbances Hormonal disturbances Allergies Associated with - Fissured tongue (50%) - Psoriasis (5%) - Reiter’s syndrome - Juvenile diabetes - Atopic dermatitis - Pityriasis rubra pilaris Pediatr Dentistry 1992;14(6):392-6.

152. Syndromes associated Reiter’s syndrome Robinow’s syndrome Aarskog syndrome Down’s syndrome Foetal hydantoin syndrome The Internet Journal of Family Practice 2011;9(2).

153. Geographic tongue

154. Geographic stomatitis Ectopic geographic tongue

155. Geographic lip Annulus migrans

156. Weathers et al (1974): All geographic lesions do not migrate erythema circinata persistans erythema circinata migrans Hacettepe Diş Hekimliği Fakültesi Dergisi 2008;32(2):73-8.

157. Classification (Hume) Type 1: Lesions on the dorsum, lateral borders and tip of tongue with possible extension to undersurface. Type 2: Geographic tongue , accompanied by geographic lesions elsewhere in the mouth . Type 3: Atypical tongue lesions whether or not accompanied by lesions elsewhere in the mouth. Type 4: Geographic lesions elsewhere in the mouth , without the presence of a geographic tongue. Hacettepe Diş Hekimliği Fakültesi Dergisi 2008;32(2):73-8.

158. Management No causal treatment May regress with time Benzydamine hydrochloride 0.15% spray or mouthwash ( Tantum ) Diphenhydramine HCl suspension (Benadryl®) Topical steroids Zinc Vitamin B Pediatr Dentistry 1992;14(6):392-6.

159. B. LEUKOEDEMA A white and veil-like alteration of the oral mucosa considered a normal variant. Etiology and Pathogenesis: Not clear

160. Clinical Findings: Bilaterally in the buccal mucosa Less clinically evident after stretching the mucosa Asymptomatic Diagnosis: Gentle stretching results in a temporary disappearance Management: 1. No treatment

161. C. WHITE SPONGE NEVUS First described by cannon in 1935 An autosomal dominant disorder Etiology and Pathogenesis: Mutations in genes coding for epithelial keratin Epidemiology: Rare disorder one in 200,000. May be present at birth or appear in child hood or young adult life .

162. Clinical Findings: A white lesion with an elevated and irregular surface comprising fissures or plaque formations Affected sites are the buccal mucosa Mucosa appears to be swollen much like a sponge or chamois leather. Asymptomatic Management: Asymptomatic, therefore no treatment Totally benign condition

163. D. HAIRY TONGUE Etiology and Pathogenesis: Unknown Predisposing factors neglected oral hygiene, shift in the microflora , antibiotics, immunosuppressive drugs, oral candidiasis, excessive alcohol consumption, oral inactivity and therapeutic radiation.

164. Clinical Findings: Impaired desquamation of the filiform papillae leads to the hairy-like clinical appearance Elongated papillae Lengths of more than 15mm have been reported in hairy tongue. Found in the posterior one third of the tongue. Colors from white to black Management: Reduction or elimination of predisposing factors removal of the elongated filiform papillae.

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