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Lecture presented 2004 to Dentists
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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
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
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 %
Mucosal Diseases
White LesionsVesiculobullous and Desquamative LesionsViral DisordersAllergic DisordersImmunopathologic DisordersDermatologic DisordersInflammatory HyperplasiasMinor Salivary Gland Tumors
White LesionsDermatosesInflammatory/infectiousKeratotic lesions
Dermatoses
Lichen PlanusLupus ErythematosusAreata MigransSolar Cheilosis (Actinic Keratosis)
Lichen Planus
.1 – 4% of populationClinical types: reticular, erosive,
ulcerativeErosive lesions less common (.16-.56 of
LP lesions
Lichen Planus
.3-3% with neoplastic conversionFluctuation over timeGenerally seen in older adults but may
occur in children
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
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 )
Lichen Planus
Lichen Planus
Lichen Planus
Lichen Planus
Lichen Planus
Lichen Planus
Dermatoses
Areata Migrans (Geographic tongue, benign migratory glossitis
Prevalence 1-2%
Multiple ‘painless’ circinate erythematous patch with whitened border
Inflammatory/Infectious
Acute Pseudomembranous CandidiasisChemical injuriesVerruca Vulgaris: Condyloma
AccuminatumSyphilitic mucous patch
Patient CM
Lesions Associated with Whiteners
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
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%
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
Leukoplakia
Vesiculobullous LesionsViral disordersAllergic disordersImmunopathologic disordersDermatologic disorders
Viral DisordersPrimary Herpetic GingivostomatitisRecurrent Herpes LabialisIntraoral Recurrent Herpes SimplexPrimary V-Z DiseaseSecondary V-Z DiseaseHerpangina
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)
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
Primary Herpetic Gingivostomatitis
Primary Herpetic Gingivostomatitis
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
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
Patient M S
Severe right face pain and ‘cold’ sores
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
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
Allergic DisordersTreatment
Discontinuation / removal of offending drug• Risks/benefits • Consult with physician
Topical corticosteroids For anaphylactic – epinephrine,
corticosteroids, antihistamines
Immunopathologic Disorders
Recurrent Aphthous StomatitisBehcet’s SyndromePemphigus VulgarisBullous PemphigoldBenign Mucous Membrane Pemphigoid
(Circitricial Pemphigoid)
Aphthous Stomatitis
Clinical characteristics Minor, major, Herpetiform Simple versus complex
Causes Trauma, smoking cessation, emotional
stress, hormones, heredity, food hypersensitivity, immune dysregulation, infectious agents
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)
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
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
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)
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)
Cicatricial Pemphigoid
Diagnosis Clinical presentation Laboratory
• Possibly useful to rule out other conditions Biopsy
• Direct immunofluorescence (subepithelial immunoreactants)
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)
Patient F
Gingival Bleeding
Dermatologic DisordersErythema MultiformeStevens-Johnson SyndromeBullous Lichen PlanusErosive Lichen PlanusDermatitis HerpetiformisEpidemolysis Bullosa
Inflammatory Hyperplasias
FibromaPyogenic GranulomaHormonal TumorEpulis FissuratumInflammatory Papillary HyperplasiaPeripheral Giant Cell GranulomaMyxofibroma
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
Mesenchymal Tumors
LipomaMyomaNerve Tumors (Neurofibroma,
Schwannoma, Traumatic Neuroma)
Tissue Discoloration
NevusMelanotic MaculeMelanomaMucoceleBlack hairy tongueSalivary tumorOther
Mucocele
Descrete non-painful swelling
M=FChildren, adolescents,
young adultsLower labial mucosa,
soft palate, retromolar region, buccal mucosa
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
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
Drug Therapy Regimes
Established by the Scientific Literature
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
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
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
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
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)
Management of Lichen PlanusIFN-alpha creamTopical Psoralen +UVA radiation Ultraviolet irradiation without
photosensitizer (320-400nm for 5-10 minutes once a week)
Management of Lichen PlanusRetinoids
Systemic: etretinate (75mg/day) Topical: tretinoin Other: temarotene (800-4800mg/day)
Surgery Conventional Cryosurgery Laser surgery Excision and grafting
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)
Management of AphthousNo treatmentTreatment of associated disease (celiac
sprue, vitamin deficiencies)Topical medicationsSystemic medications Conversion of aphthous ulcer to woundPalliative treatment (pain)Biobehavioral intervention
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
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
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)
Management of AphthousOther
Biobehavioral• Reflexotherapy (Stomatol, 1991)• Relaxation/imagery training (Psychosom med,
1990) Resumption of smoking Smokeless tobacco (role of nicotine)
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)
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)
Management of HSV-1Benadryl elixir
12.5 mg/5 mls; 1 tsp 2 minutes before each meal)
Topical anesthetics Viscous xylocaine dyclone
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