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Mucosal Disease

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Lecture presented 2004 to Dentists

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Page 1: Mucosal Disease
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Oral Pathology Reading List

Pindborg: Atlas of diseases of the oral Mucosa Shafer: A textbook of oral pathology Batsakis: Tumors of the head and neck Bhaskar: Synopsis of oral pathology Neville: Oral and Maxillofacial pathology Millard: 2nd world workshop on oral medicine

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State of the Research

Few studies assessing mucosal disease in native populations (Canada and US)

Mucosal lesions potentially increasing in prevalence *

Problems identified in school children included**:

**Oral mucosa lesions in Mazahua Indian adolescents; Banderas et al: Acta Odontol Latinoam, 1999

* Dental health findings in a Native American settlement; Staley et al: Iowa Dent J, 1993

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State of the Research

Pigmented lesions 47.6%Lingual anomalies 17.4%Developmental tooth alter 6.9%Gingival inflammatory

hyperplasia, ankilosis of tongue, lichen planus, focal epithelial hyperplasia and double lip 24 %

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Mucosal Diseases

White LesionsVesiculobullous and Desquamative LesionsViral DisordersAllergic DisordersImmunopathologic DisordersDermatologic DisordersInflammatory HyperplasiasMinor Salivary Gland Tumors

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White LesionsDermatosesInflammatory/infectiousKeratotic lesions

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Dermatoses

Lichen PlanusLupus ErythematosusAreata MigransSolar Cheilosis (Actinic Keratosis)

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Lichen Planus

.1 – 4% of populationClinical types: reticular, erosive,

ulcerativeErosive lesions less common (.16-.56 of

LP lesions

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Lichen Planus

.3-3% with neoplastic conversionFluctuation over timeGenerally seen in older adults but may

occur in children

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Lichen Planus

Erosive lesions and systemic disorders Malignancies Gastrointestinal disease Primary biliary cirrhosis Chronic active hepatitis (Hepatitis C) Ulceratiave colitis Diabetes mellitus Autoimmune disease Drug reactions GVHD

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Lichen Planus

Clinical presentation Symptoms Location

• Buccal mucosa, dorsal tongue, gingiva, lips, floor of the mouth, soft palate, lateral tongue

Tissue quality• Keratotic (papular, plaque-like, linear, reticular,

annular• Vesiculo-bullous (atrophic, erosive )

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Lichen Planus

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Lichen Planus

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Lichen Planus

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Lichen Planus

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Lichen Planus

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Lichen Planus

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Dermatoses

Areata Migrans (Geographic tongue, benign migratory glossitis

Prevalence 1-2%

Multiple ‘painless’ circinate erythematous patch with whitened border

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Inflammatory/Infectious

Acute Pseudomembranous CandidiasisChemical injuriesVerruca Vulgaris: Condyloma

AccuminatumSyphilitic mucous patch

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Patient CM

Lesions Associated with Whiteners

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Keratotic Lesions

PapillomaBenign Keratosis: Verruciform

Hyperkeratosis; Linea alba; Cheek biting; Hairy tongue

Epithelial Atypia; Carcinoma-in-Situ; And Squamous cell carcinoma

Nicotinic Stomatitis; Tobacco Keratosis; Verrucous carcinoma

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Sensitivity and specificity of OraScan toluidine blue mouthrinse in the detection of oral cancer and precancer. J Oral Pathol Med 1996

N = 145 Asian patientsReady to use kit: OroScanOral carcinomas = 100% sensitivityOral dysplasias 79% sensitivitySpecificity 62%

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Concomitant Leukoplakia in patients with oral squamous cell carcinoma. Oral diseases. 1999

N = 100 patients with oral squamous cell carcinoma

47% with concomitant leukoplakia 36% with leukoplakia adjacent to site11% with leukoplakia distant to siteConclusion: early detection and

management of oral leukoplakia may be preventative

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Leukoplakia

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Vesiculobullous LesionsViral disordersAllergic disordersImmunopathologic disordersDermatologic disorders

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Viral DisordersPrimary Herpetic GingivostomatitisRecurrent Herpes LabialisIntraoral Recurrent Herpes SimplexPrimary V-Z DiseaseSecondary V-Z DiseaseHerpangina

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Primary Herpetic Gingivostomatitis

Fever and lymphadenopathyMultiple painful erythematous ulcerationsLocalized to the cheek, tongue, lips, palate,

and importantly – attached gingivaBilateralConfirm with viral culture Acyclovir elixir, famcyclovir* and valacyclovir

(*may reduce latent infection with simplex 1)

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A prospective study of new infections with herpes simplex virus Type 1 and 2. Chiron HSV Vaccine Study Group. N Engl J Med 1999 4;341(19):1432

2393 sexually active HSV-2 seronegative persons monitored for evidence of new HSV infection

40% of new HSV-2 and 2/3 of new HSV-1 are asymptomatic.

In sexually active adults new HSV-1genital infections as common as oropharyngeal HSV-1 infections

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Primary Herpetic Gingivostomatitis

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Primary Herpetic Gingivostomatitis

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Viral DisordersIntraoral Recurrent Herpes Simplex

Clinical Characteristics• Initial burning sensation• Multiple punctate ulcers which coalesce• Localized to the attached gingiva in a well

defined area• Moderate to severe pain• 10-14 day duration with complete

resolution/recrudesemce

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The probability of in vivo reactivation of herpes simplex virus type 1 increases with the number of latently infected neurons in the ganglia; J virol 1998

Animal study: miceThe number of animals that

experienced virus reactivation was positively correlated with the number of latently infected neurons in the ganglia

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Patient M S

Severe right face pain and ‘cold’ sores

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Vericella Zoster (Shingles)

UnilateralClusters of vesiclesDyesthesia initially then severe pain7-10 day course with scarring – lesions

persisting for up to 5 weeksConcern re osteonecrosis and tooth

devitalizationPost-herpetic neuralgia

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Allergic DisordersStomatitis Venenata (contact)Stomatitis Medicamentosa (drug)

Erythema multiforme Anaphylactic stomatitis Intraoral fixed drug reactions Lichenoid drug reactions Lupus erythematosus like reactions Pemphigus-like drug reactions Non-specific vesiculoulcerative lesions

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Allergic DisordersTreatment

Discontinuation / removal of offending drug• Risks/benefits • Consult with physician

Topical corticosteroids For anaphylactic – epinephrine,

corticosteroids, antihistamines

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Immunopathologic Disorders

Recurrent Aphthous StomatitisBehcet’s SyndromePemphigus VulgarisBullous PemphigoldBenign Mucous Membrane Pemphigoid

(Circitricial Pemphigoid)

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Aphthous Stomatitis

Clinical characteristics Minor, major, Herpetiform Simple versus complex

Causes Trauma, smoking cessation, emotional

stress, hormones, heredity, food hypersensitivity, immune dysregulation, infectious agents

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Aphthous Stomatitis

Associated systemic disorders Behcet’s disease MAGIC syndrome FAPA syndrome Cyclic neurtropenia HIV, Reiter’s syndrome Hematinic deficiencies Celiac disease (sprue, gluten-sensitivity) Inflammatory bowel disease, Chohn’s disease)

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Behcet’s Syndrome

Clinical characteristics Deep ulcerative lesions (25-75% cases);

long lasting Soft palate, oropharynx Ocular (90%) and genital lesions Arthritis (knees,wrists, elbows, ankles) Central nervous system Vasculitis multisystem abnormality

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Behcet’s Syndrome

Etiology Immunodysregulation related to triggers:

environmental antigens (strep, virus, pesticides, heavy metals

Genetic vulnerability (mucocutaneous associated with HLA-b12 and frequently seen in USA; Ocular in Japan and middle eastern countries

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Behcet’s Syndrome

Diagnosis Oral ulcers 3x in prior year + Two of the following:

• Recurrent genital ulceration• Ocular lesions• Cutaneous lesions or positive pathergy

test following injection of inert substance (skin hyperreactivity)

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Cicatricial Pemphigoid

BMMP, Mucous Membrane Pemphigoid, Desquamative gingivitis

Etiology: unknownClinical features

Older adults; females > males Oral sites but can involve nasal, esophageal,

laryngeal, vaginal mucosa Initial vesicles/bullae which rupture and result in

generalized denuded mucosa with pain Occular involvement (inflammation and scarring)

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Cicatricial Pemphigoid

Diagnosis Clinical presentation Laboratory

• Possibly useful to rule out other conditions Biopsy

• Direct immunofluorescence (subepithelial immunoreactants)

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Cicatricial Pemphigoid

Differential diagnosis Linear IgA Disease

• Deposition of IgA along the basement membrane zone

Epidermolysis Bullosa Acquista• Antibodies directed against type VII collagen• Localized on the floor of the Bulla (versus the

roof)

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Patient F

Gingival Bleeding

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Dermatologic DisordersErythema MultiformeStevens-Johnson SyndromeBullous Lichen PlanusErosive Lichen PlanusDermatitis HerpetiformisEpidemolysis Bullosa

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Inflammatory Hyperplasias

FibromaPyogenic GranulomaHormonal TumorEpulis FissuratumInflammatory Papillary HyperplasiaPeripheral Giant Cell GranulomaMyxofibroma

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Minor Salivary Gland Tumors

Epithelial Adenomas (Pleomorphic, Monomorphic) Mucoepidermoid Tumor Acinic Cell Tumor Carcinoma

• Adenoid Cystic Carcinoma• Adenocarcinoma• Epidermoid Carcinoma• Carcinoma in Pleomorphic Adenoma

Nonepithelial TumorsOther

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Mesenchymal Tumors

LipomaMyomaNerve Tumors (Neurofibroma,

Schwannoma, Traumatic Neuroma)

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Tissue Discoloration

NevusMelanotic MaculeMelanomaMucoceleBlack hairy tongueSalivary tumorOther

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Mucocele

Descrete non-painful swelling

M=FChildren, adolescents,

young adultsLower labial mucosa,

soft palate, retromolar region, buccal mucosa

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Oral MelanomaOccur on the palate and gingiva 80%Adults; Men>womenEarly recognition improves prognosisClinical features

Brownish/black discoloration Normal surface texture or uleration (but without

rolled borders or induration) Slight swelling Regional nodal involvement Metastases to liver or lung

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Vegetable and fruit consumption and cancer rusk. Int-J-Cancer. 48:350, 1991

Integrated series of case control studiesMultivariate relative risks computedStrength of patterns interpreted as

suggesting that green vegetable intake is with substantial reduction of risk for common epithelial cancers

Fruit has a favourable effect on upper digestive cancers

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Drug Therapy Regimes

Established by the Scientific Literature

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Management of Lichen PlanusTo treat or not to treat

Spontaneous remission 6.5% (Silverman/OOO 1988)

Malignant transformations (2.3%) Will therapy alter conversion to malignancy Generally for asymptomatic lesions – no

treatment is necessary

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Management of Lichen PlanusIf closely associated with an amalgam:

removal of offending restorationDental prophylaxis (Holstrom OOO,

1990)If lichenoid drug reaction: cessation of

offending medication

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Management of Lichen Planus

Immunomodulators Corticosteroids: topicals, intra-lesional,

systemic (40-60 x 7-10 days, tapered dose) Cytotoxics: Azathioprine (Immuran 50-

100mg) Immunosuppressants: Cyclosporin (rinse

500mg/5mls tid) Immunostimulants: Levamisole

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Management of Lichen Planus

Medication combinations• levamisole and prednisolone (Lev 50mg

tid/prednisolone 5mg tid x 3 days)• Dexamethasone-cyclophosmphamide

pulse therapy ( 100 mg dexamethasone x 3 days and 500 mg cyclophosphamide x 1 day repeating every 4 weeks), used for pemphigus

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Management of Lichen PlanusAnti-microbials

Antibiotics: Doxycycline, Acromysin Antifungals

• Clotrimazole • Griseofulvin 250mg bid 8-10 days (if candida interaction)

Anti-malarials: Dapsone (50mg/day) Anti-virals: interferon beta or alfa-2b Anti-malarial: Hydroxychloroquine sulfate

(plaquenil) 200-400mg daily (may require 3-6 months)

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Management of Lichen PlanusIFN-alpha creamTopical Psoralen +UVA radiation Ultraviolet irradiation without

photosensitizer (320-400nm for 5-10 minutes once a week)

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Management of Lichen PlanusRetinoids

Systemic: etretinate (75mg/day) Topical: tretinoin Other: temarotene (800-4800mg/day)

Surgery Conventional Cryosurgery Laser surgery Excision and grafting

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Management of Lichen PlanusPain control

Benadryl syrup (50/50) with Maalox OTC or prescribed medication

Biobehavioral intervention Stress reduction Reduction in physical activity Management of anxiety and depression (if

confounding presentation)

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Management of AphthousNo treatmentTreatment of associated disease (celiac

sprue, vitamin deficiencies)Topical medicationsSystemic medications Conversion of aphthous ulcer to woundPalliative treatment (pain)Biobehavioral intervention

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Management of AphthousTopical approaches

Corticosteroids• Kenalog in Orabase .1%, Lidex in orobase• Decadron elixir 0.5mg/5mls• Clobetasol propionate (with or without vehicle)• Aqueous hydrocortisone mouthwash

Antibacterials• Tetracycline rinses (125mg/5mls)• Listerine / Peridex • Mouthrinse with triclosan

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Management of AphthousTopical approaches

Sodium Lauryl sulfate in toothpaste Sulcralfate (not efficacious) Laser ablation Silver nitrate Amlexanox oral paste (Aphthasol) Benadryl elixir (12.5mg/5mls) or syrup (with

kaopectate)/ Rothwell’s solution 5% 5-aminosalicylic acid as a cream Bioadhesive patches

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Management of AphthousSystemic approaches

Naturopathic preparations• Longo vital ® (6 herbs)• Zinc supplementation• Lactobacillus acidophilus preps(Bacid, Lactinex)

Immunomodifiers• Corticosteroid

– Prednisolone – pulse / prednisone 40-60mg with 7 day taper

• Azelastine (azelastine hydrochloride)• Thalidomide (50-300mg/day) (also for Bechet’s)

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Management of AphthousOther

Biobehavioral• Reflexotherapy (Stomatol, 1991)• Relaxation/imagery training (Psychosom med,

1990) Resumption of smoking Smokeless tobacco (role of nicotine)

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Management of CandidaAntifungals

Nystatin (Mycostatin oral suspension, 100,000units/ml; 5 mls 4-5x/day

Clotrimazole (Mycelex 10mg; 5x/day Miconazole Ketoconazole (Nizoral 200mg; 1 tab/day

x10d) Diflucan 100mg (2tabs initially – 1 tab/day x

14days)

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Management of HSV-1Acyclovir (Zovirax 200mg; 1cap qid x 2 weeks)Valacyclovir / famciclovir ( pharmacokinetics

different; Prophylaxis pre dental treatment – 500mg bid 1 day pre proc x 14 days)

Foscarnet (resistant to acyclovir with HIV)Immunoglobulin (may permit higher levels of

latent infection and in vivo reactivation)Interferon (potential protective effect)Medicinal Plants (Thai, Turkish, Brazilian,

Indonesian, South American)

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Management of HSV-1Benadryl elixir

12.5 mg/5 mls; 1 tsp 2 minutes before each meal)

Topical anesthetics Viscous xylocaine dyclone

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Management of HSV-1Systemic support therapy (fluids, rest,

proteins, vitamin and mineral food supplements)

Narcotics Vicodin ( 1 tab qid prn pain) Lortab 5-10mg Demerol 50 mg Percodan