Oral mucosal lesions

Discussion on various oral mucosal diseases from an oral and maxillofacial surgeon's point of view

1. Oral Mucosal Lesions Presented by: Dibya Falgoon Sarkar (Dept. of Oral & Maxillofacial Surgery)

2. Contents According to Burket oral mucosal lesions can be broadly classified into: Red and white lesions Pigmented lesions Ulcerative, vesiculous and bullous lesions

3. Red and white lesions Infectious diseases: Oral candidiasis Oral hairy leukoplakia Premalignant disorders: Oral leukoplakia and erythroplakia Oral submucous fibrosis Immunopathologic diseases: Oral lichen planus Lichenoid reactions Lupus erythematosus Toxic reactions: Tobacco pouch keratosis Nicotinic stomatitis Reactions to mechanical trauma: Morsicatio Frictional keratosis Others: Benign migratory glossitis Leukoedema White sponge nevus

4. Oral Candidiasis (Thrush) Usually caused by the normally present Candida albicans which becomes pathogenic because of altered host defense system. Systemic factors Local factors Diabetes , advanced systemic disease Use of dentures Xerostomia- Drugs or radiation Reduced vertical dimension Sjogren syndrome Overuse of antibiotic mouthrinses HIV infection & AIDS Lip-licking habit Systemic antibiotic, corticosteroid therapy

5. Classification of oral candidiasis Primary oral candidiasis Secondary oral candidiasis Pseudomembranous HIV-AIDS Erythematous Familial chronic mucocutaneous disease Chronic plaque like DiGeorge syndrome Denture stomatitis Candidiasis endocrinopathy syndrome Angular chelitis Median rhomboid glossitis Hyperplastic

6. Clinical presentations of oral candidiasis Angular cheilitis Median rhomboid glossitis Denture stomatitis Hyperplastic Pseudomembranous Erythematous

7. Differential diagnosis Leukoplakia - A leukoplakia will always remain adherent to the mucosa on rubbing. Candidiasis generally presents as pseudomembrane Oral lichen planus- Generally presents as a reticular striae (Wickham’s striae ) and is adherent on rubbling . Often presents with a burning sensation Secondary syphilis- Generally associated with a primary chancre over site of inoculation Chemical/ heat burns

8. Diagnosis and treatment Investigation- Tissue biopsy stained with PAS stain/ KOH mount, Fungal culture Treatment- (according to Marx & Stern) Mild forms : Clotrimazole oral solution 5ml 3-4times daily for 2 weeks Chronic well established : Nystatin oral suspension (1lacU/ml, 5ml, 4 times daily) along with Clotrimazole troches (10mg, 5times daily) Refractory forms : Fluconazoles (100mg capsules once daily, 2 weeks) 3. Disseminated forms: Amphotericin B i.v. with D5 solution at a rate of 0.2-0.7 mg/kg/day. But it can lead to nephrotoxicity

9. Oral hairy leukoplakia Oral hairy leukoplakia is the second most common HIV-associated oral mucosal lesion Associated with low CD4 T– lymphocyte count Etiology - Epstein-Barr virus Prevalance - Prior to HAART era it was around 25% In AIDS patients it is around 80% Male> Female Prevalent in smokers

10. Clinical features, Diagnosis, Treatment Site predilection- Lateral borders of tongue Vertical white folds which cannot be scraped off Asymptomatic condition Diagnosis- Biopsy Treatment- Antiviral medication

11. Premalignant disorders Premalignant lesions: Oral leukoplakia Erythroplakia Reverse smoker’s palate Premalignant conditions: Oral submucous fibrosis Oral lichen planus

12. Oral leukoplakia Oral leukoplakia is defined as a white plaque of questionable risk having excluded other known diseases or disorders that carry no risk for cancer Etiology : Smoking, use of tobacco products, alcohol abuse which cause genetic changes in the oral mucosa Prevalence- 2.6% Mean age- 30-50 years Sex predilection: Men > Women Found in all oral sites. High-risk sites for malignant transformation: Floor of Mouth Lateral borders of tongue

13. Types of oral leukoplakia Homogenous Nonhomogeneous White, well-demarcated plaque with identical pattern throughout the entire lesion Presents as patches /plaques intermingled with red elements Often termed as erythroleukoplakia / speckled leukoplakia Increased chances of malignant transformation

14. Classification and Staging of Oral L eukoplakia Van der Waal et al., Journal of Oral oncology (2000) L (size of leukoplakia ) L1: Size of single/ multiple leukoplakias together ≤ 2cm L2: Size of single/ multiple leukoplakias together 2-4cm L3: Size of single/ multiple leukoplakias together ≥4cm P (pathology) P0: No epithelial dysplasia P1: Distinct epithelial dysplasia present Staging: Stage I: L1Po Stage II: L2Po Stage III: L3Po or L1/L2P1 Stage IV: L3P1

15. Management of oral leukoplakia Prognosis of leukoplakia patients is decided by: Size of lesion Homogeneous/non-homogeneous pattern According to Burket , lesions <200sq.mm shows better prognosis Cryotherapy can be used by it has limitations with depth control L aser surgery and fulguration is widely used to eradicate leukoplakia and erythroplakia but tissue specimen for biopsy is not available. According to Marx & Stern, leukoplakias which are graded as moderately dysplastic/ carcinoma in-situ are managed with surgical excision with 1cm margin regardless of size

16. According to van der Waal et al Provisional clinical diagnosis of leukoplakia Elimination of possible cause (2-4 weeks observation) No possible cause (Definitive clinical diagnosis) Good response No response (Definitive clinical diagnosis) Biopsy Definable lesion Management accordingly No d efinable lesion Dysplasia/No dysplasia D efinable lesion Management accordingly Treatment/ Observation Follow-up

17. Proliferative verrucous leukoplakia PVL is a field cancer phenomenon by which clinically normal-appearing oral mucosa slowly transforms through advancing stages of clinical leukoplakia , verrucous hyperplasia/ carcinoma, and then into invasive SCC More common in older women(4:1) Lower gingiva is a predilection site Most patients (78 %) are usually non smokers High recurrence rate High malignant potential Increased correlation with oral Candida infection

18. Diagnostic work-up & Management of PVL Diagnosis mainly dependent on biopsy Principles of PVL excisions differ from other leukoplakias : Clear all peripheral margins Areas of excision often cover large surfaces and thus split-thickness skin graft may be necessary after excision Chemoprevention with fluconazole oral suspension and selenium (100microgram daily) Literature shows bad prognosis in laser treated PVL cases

19. Erythroplakia The term erythroplakia is used analogously to designate lesions of oral mucosa that present as red areas and cannot be diagnosed as any other definable lesions ( WHO, 1994 ) Rare premalignant lesion with a prevalence of 0.09% (Acc. to Shafer & Waldron) Age predilection: 6 th -7 th decades of life Male: Female - 1:1 Site: Common in soft palate, buccal mucosa and floor-of-mouth Aetiology: Same as those associated with squamous cell carcinoma

20. Erythroplakia Rare lesion with a malignant transformation rate of 26.3% (Acc. To Reddi & Shafer’s study) Treatment : Observation for 1-2 weeks following elimination of irritants. Complete excision of the lesion with clear margins down to the submucosal level is the treatment of choice Recurrence rate <5 % (Acc. To Burket ) Differential diagnosis of red lesions of oral mucosa: Mycotic infections Erythematous candidiasis Denture stomatitis Histoplasmosis Bacterial infections Tuberculosis Mucosal diseases Pemphigus, pemphigoid Atrophic lichen planus SLE Others Kaposi sarcoma Haemangioma Amelanotic melanoma

21. Oral submucous fibrosis Oral submucous fibrosis (OSF) is a collagen disorder commonly seen in the Indian subcontinent First described by Schwartz in 1952 Pindborg et al. found a prevalence of 0.2~0.5 % in India Sex predilection: 5% prevalence in women & 2% in men Areca nut (the fruit of the Areca catechu ) commonly known as betel nut or supari, plays a crucial dual role in the etiology of OSMF The attendant trismus is a result of juxtaepithelial hyalinization and secondary muscle involvement (i.e., muscular degeneration and fibrosis ) Malignant transformation has been noticed in 3-7.6% of cases

22. Pathogenesis of OSMF Areca nut Arecoline (5-7%) Tannins (11-26%) Alkaloids (0.15%-0.6%) Fibroblast proliferation Stimulates collagen synthesis Collagen fibrils resistant to collagenase

23. Clinical features and staging One of the following characteristic must be present : Palpable fibrous bands Mucosal texture feels tough and leathery Blanching of mucosa together with histologic features consistent with OSMF Differential diagnosis: Scleroderma (Widening of PDL spaces present along with skin manifestations)

24. According to Khanna-Andrade article Stage Clinical features Histology Group I The common initial symptom was a burning sensation in the mouth. Excessive salivation The mouth opening was normal in all cases. fine fibrillar collagen network was seen to be interspersed with marked edema . Blood vessels were dilated and congested epithelium was essentially normal and nonkeratinized , with occasionally some hy - perplasia Group II Interincisal openings of 26-35 mm. The soft palate and faucial pillars were the areas primarily affected. The buccal mucosa ap - peared mottled and marble-like Juxtaepithelial hyalini - zation was seen with the collagen present as thickened but separate bundles. Flattening or shortening of the epithelial rete pegs was evident with varying degrees of keratinization

25. Stage Clinical features Histology Group III: moderately advanced cases Trismus was evident, with an inter- incisal opening of 15-25 mm Vertical fibrous bands could be palpated in the premolar area. Juxtaepithelial hyalini - zation was present. Thickened collagen bundles were faintly discernible, separated by very slight, residual edema Muscle fibers were seen to be interspersed with thickened and dense collagen fibers . Group IVa Trismus was severe with an interincisal opening of 2-15 mm. The fauces was thickened, shortened, and firm to palpation, with the tonsils compressed between the fibrosed pillars. Shrunken uvula Collagen was hyalinized as a smooth sheet eliminating all evidence of individual bundles. Extensive fibrosis had obliterated the mucosal blood vessels and eliminated the melanocytes, a feature which explained the clinically observable loss of pigmentation Group IVb advanced cases with premalignant and malignant changes

26. Management of OSMF Actively discourage patients from consuming areca nut and other chronic irritants such as hot and spicy foods Well balanced diet with vitamin A & B-complex substitutes Wherever possible we extract the third molars Group I & II patients are put on conservative therapy and active physiotherapy Group III & IV patients are treated by surgical intervention

27. Conservative therapy in OSMF Physical therapy: Physical exercise Microwave diathermy Medical therapy: Modulators of inflammation: Corticosteroid Interferon gamma Placental extracts Modulators for vascularity: Pentoxiphylline Nylidrin Fibrinolysis: Hyaluronidase Collagenase Nutritional support and antioxidants: Beta-carotene Lycopene Vitamins Ayurvedic treatment: Turmeric Tea pigments

28. Conservative therapy in OSMF Corticosteroid therapy: Submucosal injections of triamcinolone acetonide (40 mg) injected into the faucial pillars, retromolar area, and buccal mucosa . On average, a dose of 150-200 mg of local submucosal corticosteroid injection was given in divided doses at 10-day intervals for a period of 2-3 months. Hyaluronidase(1500 I.U)- 0.5ml injected intralesionally twice a week for 10 days Placental extract ( Placentrex )- 2ml intralesional once a week along with iodine and vitamin B complex

29. Surgical management Rationale: Incision or surgical release of fibrous bands followed by forceful opening of mouth, and covering the surgical defects using various flaps and biosynthetic materials In some cases we may need temporalis myotomy and bilateral coronoidectomy Extraoral flaps Intraoral flaps Microvascular Alloplasts Split thickness skin grafts Tongue flap ALT flap Collagen membrane Temporalis muscle / fascia pedicled flap Palatal island flap Radial forearm free flap Artificial dermis Nasolabial flap Buccal fat pad Amnion graft

30. Review of literature Khanna & Andrade found disappointing results with split thickness skin grafting as they found marked shrinkage. They advocated bilateral palatal flaps . Borle & Borle also encountered disappointing results with skin grafts. They used tongue flaps . But OSF patients show tongue involvement in 38% cases and post op morbidities are more with tongue flaps Andrade et al. and Mehrotra et al. concluded that nasolabial flaps cannot extend adequately to cover the raw area and they also cause facial scars Yeh et al. used pedicled buccal fat pad as it provided excellent function without deteriorating esthetics

31. Verrucous carcinoma Verrucous carcinoma is a distinct low grade variant of squamous cell carcinoma of oral cavity (According to Oral & maxillofacial surgery clinics- 2006) First identified by Ackerman in 1948. Rare tumor representing 3-4% of all oral carcinomas Etiology - High incidence associated with use of tobacco products 16-51% of oral VCs are found in persons without tobacco habits HPV is thought to be one of the causative agent

32. Clinical presentation of verrucous carcinoma (VC) True VCs are slow-growing, painless, broad-based wart-like papillary lesion Site: buccal mucosa (60% cases), Gingiva (30%) Male predilection seen Age: Older than 50 years Shows high propensity of local invasion rather than metastatic spread Evidence of osseous invasion has been found I nflammatory regional lymph nodes may be seen in some cases

33. Treatment of Verrucous Carcinomas Excision to a depth of full thickness of mucosa is the treatment of choice for oral VCs According to Marx & Stern excisional depth: Buccal mucosa: U pto buccinator fascia Gingiva: Upto a supraperiosteal plane Posterior and floor of mouth lesions are excised with a 2cm margin Unlike squamous cell carcinomas VCs shows less radiosensitivity Transformation of VCs into SCCs have been seen after radiation therapy Recurrance rate: 26-57%

34. Oral lichen planus (OLP) Lichen planus is a T-cell mediated autoimmune interface disease in which the basal cell layer of mucosa and/or skin is attacked Prevalence varies from 0.5-2.2% Women more commonly affected Mean age at the time of diagnosis: Approx. 55yrs Premalignant condition Malignant transformation potential 0.3-3% Cutaneous lesions: 15% cases

35. Clinical types of OLP Reticular type: Characterised by Wickham’s striae of lacy, white interlacing lines Most common in buccal mucosa Asymptomatic Papular type : Clinically characterised by small white dots which intermingle with the reticular pattern Plaque type: Homogeneous well-demarcated white plaque, asymptomatic

36. Clinical types of OLP Erosive/atrophic type: Characterised by intense pain and mucosal inflammation Presents as desquamative gingivitis Ulcerative type: Most disabling form of OLP Fibrin coated ulcers surrounded by erythematous zones and white striae in periphery Bullous type: Presents as bullous lesions surrounded by W ickham’s striae

37. WHO diagnostic criteria for OLP (1978) Clinical criteria Presence of white papules, anular , reticular, plaque-like lesions, gray -white lines radiating from the papules Presence of a lace-like network of slightly raised gray -white lines (reticular type) Presence of atrophic lesions with/without erosions may also have bulla

38. WHO diagnostic criteria for OLP (1978) Histologic criteria Presence of thickened orthokeratinised / parakeratinised layers in sites that are normally keratinised Presence of Civatte bodies in basal layer, epithelium and superficial part of connective tissue Presence of a band-like zone of cellular infiltration in the superficial connective tissue, consisting mainly lymphocytes Signs of liquefaction degeneration in basal layer

39. Differential Diagnosis of OLP Papules/ reticular components have to be present in order to establish correct clinical diagnosis Differential diagnosis: Discoid lupus erythematosus: Presents with hyperkeratinisation, striae abruptly terminate against a sharp demarcation Pemphigus: Ulcerative type OLP have same presentation Leukoplakia Oral candidiasis

40. Management of OLP Reticular and plaque forms do not require treatment other than reassurance and follow-up Milder forms of erosive type are managed with topical corticosteroids like clobetasol propionate/1% triamcinolone paste Topical application of cyclosporine, tacrolimus and retinoids have been suggested as second-line of treatment Systematic corticosteroid therapy with oral prednisolone may be used in extensive cases. But steroids have their side-effects Short-term effects Long term effects Hypertension, hyperglycaemia, infections, peptic ulcer, hypernatremia Muscle wasting, delayed wound healing, osteoporosis, cataracts

41. Systemic corticosteroid therapy protocols Regimen I Regimen II Regimen IIIA Regimen IIIB Oral Prednisolone 1.5mg/kg/day for 2 weeks followed by tapering by 20mg/day each week until a 20mg /day dose is reached. The dose is followed for 1month followed by 10mg/day for 3 months, followed by 5mg every other day for 6 months Oral prednisolone 100-120 mg/ day for 2 weeks after which the drug is stopped abruptly Disadv : Frequent exacerbations Oral prednisolone 100-120 mg/ day for 2 weeks A tapering schedule reduces prednisone by 20mg/day each week until lowest possible level is reached without exacerbating the disease Resistant pemphigus cases Oral prednisolone 100-120 mg/ day for 2 weeks A tapering schedule reduces prednisone by 20mg/day each week until a level is reached at which the disease is exacerbated Combined with other immunosuppressive drugs to reduce side effects Preferred in Steven Johnson syndrome Useful in patients with life long steroid need Useful regimen in patients who cannot tolerate high dose steroids

42. Drug-induced Lichenoid Reactions Lichenoid reactions represent a family of lesions with different etiologies with a common clinical and histologic appearance Etiology and pathogenesis: DILRs resemble a delayed hypersensitivity reaction where the drugs and their metabolites have the capability to act as haptens and trigger lichenoid reactions Clinically appears similar to cutaneous LP and may be pruritic DILRs are not life-threatening like Toxic epidermal necrolysis Common drugs ACE inhibitors Antimalarials Penicillin group Gold and heavy metals Sulphonamides OHA and OCPs Rifampicin

43. Drug-induced Lichenoid Reactions Management of drug-induced lichenoid reactions: Discontinuation of the drug and symptomatic treatment with topical steroids Patients must be cautioned of future use of same drugs

44. Systemic Lupus Erythematous SLE is an autoimmune disorder in which antigen-antibody complexes become entrapped in the capillaries of most organs. These complexes initiate the complement cascade and inflammation Marked female predilection (90%) seen Peak incidences between 20-40 years Most characteristic signs- Malar butterfly rash Positive serum ANA test Pathogenesis: Development of autoantibodies against native double stranded DNA . There marked depletion of complement proteins

45. ACR diagnostic criteria for SLE Serositis Oral ulcers Arthritis Photosensitivity Blood disorders- Lymphopenia, leukopenia, thrombocytopenia Renal disorders- 0.5g/2h protonectin , cellular casts in urine Anti-nuclear antibody positivity Immunologic disorders Neurologic disorders- seizure, psychosis Malar rash Discoid rash At least 4 of these 11 criteria must be present before definitive diagnosis of SLE can be made along with a positive serum ANA test Oral ulcers are red shallow ulcers commonly found in palate and marginal gingiva

46. Differential diagnosis of SLE Erythema multiforme Discoid lupus erythematosus Rheumatoid arthritis Drug-induced lupus syndrome: Males are equally affected No neurologic/renal components Anti- native DNA antibodies not present Symptoms improve on stoppage of the drug

47. Treatment of SLE Mild forms of SLE are managed by supportive care. NSAIDS are given in mild flare-ups. Hydroxychloroquine 400mg orally is used to alleviate symptoms Severe forms with multi-organ involvement are managed with systemic prednisone( systemic corticosteroid therapy IIIA & IIIB) Mycophenolate and cyclophosphamide may be added to these regimen to reduce the steroid requirement.

48. Topical therapy for Oral lesions of SLE Drugs Direction for use 0.05% Clobetasol gel Place on affected area(s) 2 times/ day for 2 weeks Triamcinolone acetonide 5mg/ml Intralesional injection Topical clotrimazole troches (10mg) Dissolve in mouth 5 times/day for 10 days Chlorhexidine rinse (0.12%) Swish and spit 10ml twice daily until lesions resolve Adapted from Brennan et al.

49. Discoid lupus erythematosus Also known as chronic cutaneous lupus erythematosus Immune-based disease primarily targets skin and to lesser degree, mucosa. Lesions show similar characteristics and site predilection like that of SLE Differential diagnosis: SLE (No ANAs, hypocomplementia found) Psoriasis 3. Skin TB 4. Leprosy Treatment: Topical corticosteroids and preventive measures are taken in mild forms Severe forms are treated with systemic steroid regimens I & II

50. Nicotinic stomatitis/ Smoker’s palate S moker’s palate initially presents as erythematous irritation and later transforms into a whitish palatal mucosa reflecting a hyperkeratosis Reds dot can be observed representing inflamed orifices of accessory salivary gland ducts which can be enlarged and metplastic Etiology and pathogenesis: Seen in cigar and pipe smokers but not in cigarette smokers Caused due to a combined effect of heat and tobacco products, Not a premalignant lesion Treatment : Cessation of smoking

51. Leukoedema Leukoedema is a white and veil-like alteration of the oral mucosa Asymptomatic condition with no malignant potential Etiology is not clear Unlike leukoplakia , it is more diffuse and temporarily disappears on stretching Requires no treatment

52. White sponge nevus Rare autosomal dominant disorder Caused due to mutation of genes coding for epithelial keratin formation Clinical features: White lesions with elevated and irregular surface Commonly seen in buccal mucosa Histologically spinous epithelial cells show marked intracellular edema and are nondysplastic Management: Benign, asymptomatic

53. Benign Migratory Glossitis/ Geographic tongue Annular lesion affecting the dorsum and margins of tongue Unknown etiology, equal gender distribution Prevalence 1-2.5% of all oral lesions Clinical features: Circumferentially migrating lesions with erythematous areas of depapillated tongue Peripheral zones are white and elevated Aggravates in periods of stress Mostly asymptomatic Self healing lesions Symptomatic patients are given topical anesthetics

54. Pigmented lesions of oral mucosa Hairy tongue Malignant melanoma Haemochromatosis Peutz-Jegher’s syndrome Melasma Amalgam tattoos Endogenous pigmentation

55. Hairy tongue Etiology is unkown in most cases Probable causes are: Poor oral hygiene Use of antibiotics / immunosuppressant drugs Therapeutic radiation Excessive alcohol consumption Smoking habits Clinically presents as an impaired desquamation of the filiform papilla which leads to elongated papilla over dorsum of tongue Pigmentation mainly comes from the oral microflora Patients experience physical discomfort Treatment: Use of tongue scrappers

56. Malignant melanoma Melanomas comprise of a rare group of aggressive, malignant neoplasms which are mainly found in skin of white people Oral mucosal melanomas comprise of 0.2-8% of all melanomas diagnosed, commonly f ound in males more than 45 years age Metastasis is predominantly via haematogenous routes Site: Most common site is palate followed by the maxillary gingiva Nevus Melanoma Symmetry Asymmetry Borders regular Irregular borders Uniform color Color variegation Diameter static Diameter enlargement (>6mm) Color stable Evolution to darker pigment

57. Clinical types of Oral Melanomas Superficial spreading Most common between 40-60 years age Initiallly looks like a nevus but later develop irregular border and odd shape This radial growth pattern later changes Acral lentiginous Rarely found in oral cavity Characterised by a flat papular lesion with areas of nodularity (Vertical component Nodular melanoma Most common between 50-70 years of age Common in men Shows vertical growth Poor prognosis Occasionally present as a flesh colored mass,amelanotic melanoma

58. Breslow’s measurement of tumor thickness Thickness (mm) Risk of recurrence <0.76 Low risk 0.76-1.50 Low to intermediate risk 1.51-3.99 Intermediate to high risk >4.00 High risk Indicators of poor prognosis: Surface ulceration High mitotic index Absence of lymphocyte infiltrations Distant/ regional metastasis Five year survival rate in patients with metastatic melanoma is <15%

59. Treatment of oral melanomas According to Marx & Stern wide local excision with 3-5cm margins is the treatment of choice. Neck dissection is to be done in cases with cervical lymph node metastasis According to Burket adjuvant chemotherapy with alpha 2B interferon is approved in cutaneous melanoma cases with >4mm thickness Use of adjuvant radiotherapy is a matter of debate 8 years survival rate is about 20% Lungs is the most common site of metastasis followed by skin

60. Oral Mucosal Lesions- Part II Presented by: Dibya Falgoon Sarkar (Dept. of Oral & Maxillofacial Surgery)

61. Ulcerative, vesicular and bullous lesions Frequently used terms 1. Vesicles Small blisters containing clear fluid that are less than 1cm in diameter 2.Bullae Elevated blisters > 1cm in diameter 3. Erosions Red lesions caused by rupture of vesicles/bullae or by thinning of the skin 4. Ulcers A well-circumscribed, depressed lesion with an epithelial defect 5. Pustules Blisters containing yellowish purulent matter 6. Papules Lesions raised above skin/ mucosa < 1cm in diameter 7. Plaques Raised lesions > 1cm in diameter

62. We can broadly divide these type of lesions into: Acute multiple ulcers: Herpes simplex virus Varicella-zoster Erythema multiforme Stevens- Johnson syndrome & Lyell disease Necrotizing ulcerative gingivitis & periodontitis 2. Recurring oral ulcers: Recurrent apthous stomatis Behcet syndrome 3. Chronic multiple ulcers: Pemphigus vulgaris Pemphigoid 4.Single ulcers: mostly traumatic ulcers Ulcerative, vesicular and bullous lesions

63. Herpes simplex virus infections (HSV) HSV infections are caused by the Herpesviridae family. Spreads via airborne/ direct contact. In general, infections above the waist are caused by HSV-1 and below waist by HSV-2 Pathogenesis: Primary lesion is caused by inoculation of the virus in the oral mucosa, skin and eye with infected secretions The virus then travels along the sensory neurons and causes a chronic, latent infection in sensory ganglion Recurrent herpes occurs when HSV reactivates at latent sites and travels centripetally to the mucosa/ skin

64. Clinical manifestations of HSV infection Primary herpetic gingivostomatitis : Caused mostly in children and young adults Painful vesicular lesions on mucosal surfaces Febrile, cervical lymphadenopathy Lasts for 10 days and resolve on its own Herpetic whitlow: Occupational hazard among dentists Contracted from the infected patients in the finger pads Recurrent herpes: Seen over keratinised surfaces like palate and gingiva

65. Diagnosis & management of HSV Diagnosis: Immunoslot testing detects circulating viral antibodies Viral cultures and tissue biopsy are other alternatives Treatment: Self limiting disease which remains for 7-10 days Topical 5% Acyclovir cream is helpful reduce symptoms In extensive cases, oral Acyclovir 200mg five times for 10 days. Valacyclovir has more bioavailability Differential diagnosis 1.Erythema mutiforme 2.Erosive lichen planus 3. Apthous ulcer 4. Pempigus vulgaris

66. Herpes Zoster virus infection Primary infection with varicella zoster virus leads to varicella (chicken pox). Reactivation of latent virus in the dorsal root ganglia of cranial nerves lead to herpes zoster infection/shingles. Incidence: 1.5-3 cases per 1000 cases More common in older individuals (>75 years) Transmission usually by respiratory route. Incubation period: 1-2 weeks Postherpetic neuralgia is an uncommon sequelae seen in older individuals.

67. Pathogenesis of Shingles and Postherpetic Neuralgia

68. Clinical manifestations Primary VZV infection mostly occurs in first two decades of life as maculopapular rash. HZI of skin occurs in adults and start with prodromal symptoms like deep, burning skin sensation. Within 2-4 days vesicles are seen in a dermatomal pattern unilaterally Oral & maxillofacial manifestations: Most commonly affects the ophthalmic div. of trigeminal nerve Prodromal phase is characterised by burning mucosal pain This is followed by appearance of clusters of 1-5mm ulcers which heal within 14days

69. Diagnosis & Management of HZV infections Oral swab for viral isolation using cell culture is best way for confirming diagnosis. Real time PCR can also be used Treatment: Acyclovir (800mg five times a day) Valacyclovir (1000mg three times a days) Regimen shoud be started within 72hrs of onset Postherpetic neuralgia: First line of treatment is 5% lidocaine patch and topical capsaicin Second line of treatment is with pregabalin , opioid analgesics and TCAs Case reports suggest use of botulinum toxin in PHN Vaccination of older adults reduces incidence of HZ infections.

70. Ramsay-Hunt syndrome Uncommon complication of Herpes zoster infection Involves the geniculate ganglion Clinical features: Bell’s palsy, vesicles of external ear and loss of taste sensation in the anterior two thirds of tongue Herpes zoster infections are more common in immunocompromised individuals

71. Erythema multiforme (EM) Acute, self-limited, inflammatory mucocutaneous disease. Commonly manifests in skin, oral mucosa & genitalia Represents hypersensitivity reactions to medications or infectious agents( e.g : Pneumonia, HSV, mycoplasma) Two types: (Acc. To Burket ) Erythema multiforme minor- < 10 % of total body skin Erythema multiforme major- More extensive skin & mucosal involvement

72. Clinical findings EM generally affects individuals between 20-40 years Prodromal phase is characterised with fever, malaise and headache, cough, rhinorrhea Target/ iris lesions are pathognomonic of EM Oral cavity lesions shows painful erythematous ulcerations, lips show haemorrhagic crusting

73. Management of EM Mild oral EM can be managed with systemic/ topical analgesics for pain and supportive care since the disease is self-limiting More severe cases are manged with topical/ systemic corticosteroids Acyclovir may be added if HSV infection is suspected However, Marx & Stern contraindicates the use of steroids in EM minor as they are saying use of steroids increase the chance of infections

74. Stevens-Johnson Syndrome Also known as Erythema multiforme major Life threatening and debilitating hypersensitivity Characterised by an intense vasculitis due to a combined type III & IV hypersensitivity Age: Less than 15 years Clinical features: Triad of oral, ocular and genital lesions SJS has an explosive onset and progress very rapidly Treatment: Emergency condition, requires intense supportive care Fluid resuscitation is required to prevent dehydration Systemic corticosteroids(IV methylprednisolone 500mg) along antibiotics coverage and immunosuppressive drugs Silver diazine creams are applied locally, protection of eyes

75. Necrotising ulcerative gingivitis and periodontitis Represents an acute ulcerative-inflammatory condition of the gingiva and periodontium Associated with polymicrobial infections Strong association with immune suppression, diabetes, debilitation, smoking, stress, poor oral hygiene, local trauma, etc. Etiology : Fusospirochaetal microorganisms In presence of systemic illness NUG and NUP can progress into cancrum oris / noma

76. Seven stages of ANUG - Horning & Cohen Stages Stage I Necrosis of tip of papilla Stage II Necrosis of entire papilla Stage III Necrosis extending to marginal gingiva Stage IV Necrosis extending to attached gingiva Stage V Necrosis extending to labial & buccal mucosa Stage VI Necrosis exposing alveolar bone Stage VII Necrosis perforating skin of cheek

77. Clinical features Necrotising ulcerative gingivitis have a rapid onset. First symptoms are excessive salivation, metallic taste, sensitivity of gingiva. Disease rapidly progress into extremely painful punched-out ulcers which starts from interdental papilla. Differential diagnosis: Primary herpetic gingivostomatitis Desquamative gingivitis Mucous membrane pemphigoid Laboratory tests: Gingival sulcular secretion culture.

78. Treatment Management is directed toward supportive care, pain control and identification of predisposing factors. Definitive treatment consists of gentle debridement to remove plaque and debris under LA. Hydrogen peroxide is used for killing anaerobic microbes along with chlorhexidine mouth wash. Beta lactams and Metronidazole are antibiotics of choice Patients must be tested for HIV Once the acute phase is over we perform scaling and root planing for residual plaque removal. Periodontal surgery is needed to correct the periodontal defects.

79. Aphthous Stomatitis Also known as canker sores Pathogenesis: Believed to be due to an immune-based leukoclastic vasculitis Types Clinical findings Minor Most common, <1cm, lasts for 7-14 days, no scarring is seen, occurs over free oral mucosa Major >1cm, lasts for weeks, heals with scarring Herpetiform <1cm, >10 ulcers, dispersed widely over oral mucosa Severe Same as minor, but ulcers present continuously

80. Treatment of aphthous ulcers Minor aphthous ulcers are self-limiting and requires only reassurance of the patient. Major aphthous ulcers are treated with a combination of antibiotics and systemic steroids. Marx & Stern proposes three antibiotic regimens (2-6 months): Erythromycin 250mg orally 4 times daily Doxycycline 100mg orally once daily Tetranydril elixir/ Magic mouth wash (Tetracycline 250mg+ 12.5 mg Diphenhydramine HCl per 5ml of Kaopectate If these regimens fail we generally opt for systemic corticosteroid regimen with prednisone.

81. Behcet syndrome Triad of recurring oro -genital ulcers and eye involvement Occurs in young adults, male predilection seen Diagnostic criteria: Recurrent oral ulcers: Aphthous type ulcers which occur atleast 3 times in I year period Plus 2 of the following: Eye lesions: Uveitis, retinal vasculitis and hypopyon Skin lesions: Papulopustular genital lesions Positive pathergy test Treatment: Systemic corticosteroid regimen I or III with prednisone

82. Pemphigus vulgaris (PV) Pemphigus vulgaris falls in a group of autoimmune, potentially life-threatening disease. Characterized by blisters and erosions of skin and mucous membranes due to intraepithelial acantholysis. Etiology : Caused due to binding of IgG autoantibodies to desmoglein 3 & 1( transmembrane adhesion molecules) present o n desmosomes. Incidence: 0.1-0.5 cases per 1 lacs per year

83. Clinical manifestations of PV Classic lesion of PV consists of a thin-walled bulla arising on an otherwise normal skin / mucosa. These bullae rupture and continue to extend peripherally leaving areas of ulcerated mucosa and denuded skin ( Lutz sign). Nikolsky sign: Pressure application on an apparently normal area of skin results in formation of a new lesion. Oral lesions precede the lesions of skin Diagnosis: Direct immunofluorescence Indirect immunofluorescence Biopsies are best done on intact vesicles < 24hrs old

84. Differential diagnosis of PV Herpes simplex virus infections: Affects young children, acute onset Erythema multiforme : Acute nature, patient gives history of taking medications in most cases, target lesions are seen Recurrent aphthous stomatitis: Aphthous ulcers are round and symmetrical. They tend to heal and recur. But in pemphigus, the same lesions continue to extend peripherally in a chronic nature. Mucous membrane pemphigoid: Distinguished by indirect immunofluorescence

85. Treatment of Pemphigus vulgaris Most important aspect is early diagnosis of the disease when lower doses of medication can be used for shorter periods of time to control the disease. High doses of systemic corticosteroids (Prednisone) are given in dosages of 1-2mg/kg/day Adjuvant therapy to reduce the side-effects of steroids include azathioprine, mycophenolate, etc. Rituximab is presently used though there are reports of high infection rates.

86. Mucous Membrane Pemphigoid Chronic autoimmune subepithelial disease which primarily affects mucous membranes Age: More than 50 years Female:Male : 2:1 Etiology : Primary lesion of MMP occurs when autoantibodies directed against proteins in the basement membrane zone cause a subepithelial split and vesicle formation. Conjuctiva is the second most common site after oral cavity. Corneal damage, symblepheron and blindness are common ocular manifestations. Desquamative gingivitis is the most common oral lesion

87. Treatment of mucous membrane pemphigoid Patients with mild oral disease are treated with topical and intralesional steroids Ophthalmologists must be consulted for the management of ocular manifestation Systemic steroid therapy regimen I & III are used in severe cases Cicatricial pemphigoid with symblepheron

88. Management of patients on Corticosteroid therapy who require Major surgery Patients who regularly take corticosteroids develop adrenal insufficiency due to depression of HPA axis. According to Hupp, Ellis & Tucker: If the pateint is currently taking steroids: Use anxiety-reduction protocol. Monitoring of vitals before, during and after surgery. Instruct patient to double usual daily dose on day before, day of, and day after surgery. On second post op day advise the patient to return to usual dose.

89. Management of patients on Corticosteroid therapy who require Major surgery According to Hupp, Ellis & Tucker: 2. If the patient is not currently taking steroids but has received atleast 20mg of hydrocortisone or equivalent for >2 weeks in past one year, Use anxiety-reduction protocol Monitoring of vitals before, during and after surgery. Instruct the patient to take 60mg hydrocortisone on the day before and the morning of surgery On the first 2 post op days, the dose should be dropped to 40mg and dropped to 20mg for 3 days thereafter. The clinician can cease administration of supplemental steroids 6 days after surgery.

90. References Burket’s Oral Medicine Oral & Maxillofacial Pathology – Marx & Stern Oral & Maxillofacial Surgery Clinics of North America (2006 issue) Van der Waal et al., Journal of Oral oncology ( 2000) Khanna, Andrade: Oral submucous fibrosis : A new concept of management: Report of 100 cases; IJOMS 1995