oral ulceration and vesiculobullous diseases1and 2

Oral Ulceration and Oral Ulceration and Vesiculobullous DiseasesVesiculobullous Diseases

Dr. Rima SafadiDr. Rima Safadi

20102010

Ulcer Definition:Ulcer Definition:

Localized defect in the surface epithelium Localized defect in the surface epithelium exposing an inflamed connective tissue baseexposing an inflamed connective tissue base

Most common lesion of the oral mucosaMost common lesion of the oral mucosa May be a manifestation of many disease entitiesMay be a manifestation of many disease entities

Erosion: is a superficial ulcerErosion: is a superficial ulcer

Causes of oral ulcerationCauses of oral ulceration

InfectiveInfectiveTraumaticTraumaticIdiopathicIdiopathicAssociated with systemic diseasesAssociated with systemic diseasesAssociated with dermatologic diseasesAssociated with dermatologic diseasesNeoplastic Neoplastic

Keep them in mind when thinking of D/D of an Keep them in mind when thinking of D/D of an ulcerulcer

Traumatic Ulceration Traumatic Ulceration

MechanicalMechanical

ChemicalChemical

ThermalThermal

FactitiousFactitious

RadiationRadiation

Eosinophilic ulcer (traumatic granuloma)Eosinophilic ulcer (traumatic granuloma)

Mechanical UlcerationMechanical Ulceration

Three criteria for diagnosisThree criteria for diagnosis1.1. Define a causeDefine a cause2.2. Fit size, shape and location of ulcerFit size, shape and location of ulcer3.3. Healing within 10 days of cause removalHealing within 10 days of cause removal

Chronic ulcers may look like neoplasmsChronic ulcers may look like neoplasms Deep crater like ulcer with rolled everted Deep crater like ulcer with rolled everted

margins and indurationmargins and induration When is biopsy indicated?When is biopsy indicated?

Chronic Traumatic UlcerChronic Traumatic Ulcer

Chemical UlcerationChemical Ulceration

Materials used in dental practiceMaterials used in dental practice Self treatment of oral complaints, the use Self treatment of oral complaints, the use

of aspirin, undiluted mouth washesof aspirin, undiluted mouth washes Reaction varies in severity: edema to Reaction varies in severity: edema to

necrosisnecrosis

Aspirin burnAspirin burn

Chemical burnChemical burn

Hydrogen peroxide burnHydrogen peroxide burn

Formocresol burnFormocresol burn

Anesthetic necrosisAnesthetic necrosis

Thermal UlcerationsThermal Ulcerations

Hot food or drinkHot food or drink

Factitious ulcersFactitious ulcers

RadiotherapyRadiotherapy

Damage to the epitheliumDamage to the epithelium Damage to blood vessels: atrophic and necrotic Damage to blood vessels: atrophic and necrotic

epitheliumepithelium Damage to lymphatics: edemaDamage to lymphatics: edema

Thin atrophic epithelium prone to traumatic Thin atrophic epithelium prone to traumatic ulcersulcers

Differentiate radiation ulcers (painful) from Differentiate radiation ulcers (painful) from neoplastic ulcersneoplastic ulcers

SCC

RAD mucositis

Eosinophic ulcer (traumatic Eosinophic ulcer (traumatic ulcerative granuloma)ulcerative granuloma)

Etiology: trauma and crush Etiology: trauma and crush to to musclesmuscles

Clinical appearanceClinical appearance

Histopathologic featuresHistopathologic features Sheets of histiocytes and Sheets of histiocytes and

some eosinophilssome eosinophils No relation to eosinophilic No relation to eosinophilic

granuloma of bonegranuloma of bone treatmenttreatment

Recurrent aphthous stomatitisRecurrent aphthous stomatitis

““idiopathic” or immune idiopathic” or immune mediatedmediated

Frequent recurrencesFrequent recurrences

3 types: minor major and 3 types: minor major and herpetiformherpetiform

Clinical features:Clinical features: Prodromal symptoms 1-2 Prodromal symptoms 1-2

days beforedays before Tingling sensationTingling sensation Red maculeRed macule

Study table 12.2 in your book: clinical Study table 12.2 in your book: clinical features of recurrent aphthous stomatitisfeatures of recurrent aphthous stomatitis

Minor aphthous ulcerationMinor aphthous ulceration

80% of RAS80% of RAS Affect Affect nonnon keratinized keratinized

mucosamucosa 1-5 in no1-5 in no Less than 10 mmLess than 10 mm No scarringNo scarring Recur in 1-4 monthsRecur in 1-4 months

Minor RASMinor RAS

Major aphthous ulcerationMajor aphthous ulceration

Larger >10 mmLarger >10 mm Location: Location: any where any where in in

the mouththe mouth Number 1-10Number 1-10 Healing duration 4-6 Healing duration 4-6

weeks weeks Nature: with scarNature: with scar Recur in less than 1 Recur in less than 1

monthmonth Deeper with rolled Deeper with rolled

margins D/D of OSCCmargins D/D of OSCC

Major RAS-scarringMajor RAS-scarring

Herpetiform UlcerationHerpetiform Ulceration

Least common, older age groupLeast common, older age group 1-2 mm 1-2 mm On any part of the mucosaOn any part of the mucosa No: hundredsNo: hundreds Heal in 2-3 weeks according to the sizeHeal in 2-3 weeks according to the size Scarring may occurScarring may occur Associated with Associated with severe discomfort-older severe discomfort-older

age groupage group

Etiology of RASEtiology of RAS

Most likely immune mediated Box 12.1Most likely immune mediated Box 12.1 Co factorsCo factors

Etiology of RAS (pathogenesis)Etiology of RAS (pathogenesis)

Immune mediated Immune mediated cytotoxic damage cytotoxic damage to to oral epitheliumoral epithelium

Cross reactivity Cross reactivity between bacterial between bacterial products (streptococcal) and epithelial products (streptococcal) and epithelial antigens (HSP)antigens (HSP)

T cell mediated cytotoxicityT cell mediated cytotoxicity CD4 + predominate the pre ulcerative phaseCD4 + predominate the pre ulcerative phase CD8+ cytotoxic predominate ulcerative phaseCD8+ cytotoxic predominate ulcerative phase

Etiology of RASEtiology of RASassociated factorsassociated factors

Hereditary predispositionHereditary predisposition 45% has family history45% has family history

TraumaTrauma May influence the siteMay influence the site

Emotional stressEmotional stress Precipitating factorPrecipitating factor Biting of the mucosaBiting of the mucosa

Cigarette smoking, reverse relationCigarette smoking, reverse relation


Infective agents?Infective agents? Hypersensitivity to Strep sanguis???Hypersensitivity to Strep sanguis???

or cross reactivityor cross reactivity?? Adenovirus?Adenovirus? Varicella-zoster and CMV??Varicella-zoster and CMV??

Rise of IgM at times of recurrencesRise of IgM at times of recurrences

RAS RAS associated factorsassociated factors Allergic disorders:Allergic disorders:

Food allergyFood allergy The presence of raised IgEThe presence of raised IgE

Hematological disordersHematological disorders In 20% of patients: In 20% of patients:

Iron, folic acid, B12 deficiency, Causal role?Iron, folic acid, B12 deficiency, Causal role?

Gastrointestinal diseases, Gastrointestinal diseases, Celiac disease (gluten hypersensitivity)Celiac disease (gluten hypersensitivity)

2-4%2-4% Minor typeMinor type

Ulcerative colitis and Crohn`s diseaseUlcerative colitis and Crohn`s disease


Hormonal disturbance:Hormonal disturbance: Puberty, menstruationPuberty, menstruation Pregnancy?Pregnancy?

No consistent associationNo consistent association

HistopathologyHistopathology

Infiltration by lymphocytesInfiltration by lymphocytes Damage to the epithelium and more Damage to the epithelium and more

infiltrationinfiltration Decrease in lymphocytes upon healingDecrease in lymphocytes upon healing Epithelial infiltrate is Epithelial infiltrate is T cell cytotoxic T cell cytotoxic

followed by CD4 in healing phasefollowed by CD4 in healing phase

Behcet disease (syndrome)Behcet disease (syndrome)

RAS and at least 2 of the followingRAS and at least 2 of the following Genital ulcersGenital ulcers Eye lesionsEye lesions Skin lesionsSkin lesions Pathergy test: Pathergy test: rapid inflammation due to minor rapid inflammation due to minor

traumatrauma

Pathogenesis Pathogenesis

Genetic predispositionGenetic predisposition HLA- B51HLA- B51

Immune mediated mucosal damageImmune mediated mucosal damage

VasculitisVasculitis Hyper reactivity of PMNHyper reactivity of PMN

Vesiculbullous diseasesVesiculbullous diseases

Meaning of the nameMeaning of the name Collection of clear fluid within or below the Collection of clear fluid within or below the

epitheliumepithelium Classification:Classification:

Intraepithelial Intraepithelial SubepithelialSubepithelial

Intraepithelial vesiculobullous: Intraepithelial vesiculobullous: Acantholytic: pemphigus, breakdown of intercellular Acantholytic: pemphigus, breakdown of intercellular

attachmentattachment Non acantholytic: herpetic infection, death of cellsNon acantholytic: herpetic infection, death of cells

Vesiculbullous diseasesVesiculbullous diseases

History is importantHistory is important duration, recurrenceduration, recurrence skin, eye, genital lesionsskin, eye, genital lesions medications, systemic manifestationsmedications, systemic manifestations

PemphigusPemphigus

Vulgaris is the most common typeVulgaris is the most common type Female more than maleFemale more than male Ethnic groups: Ashkenazi JewsEthnic groups: Ashkenazi Jews

PemphigusPemphigus Autoimmue: auto antibodies against Autoimmue: auto antibodies against

epithelial desmosomesepithelial desmosomes

PemphigusPemphigus

Pathogenesis: auto Ab against Pathogenesis: auto Ab against desmosomes desmosomes Desmoglein 3Desmoglein 3 Desmoglein 1 and 3 in skin and oralDesmoglein 1 and 3 in skin and oral

Activation of proteinasesActivation of proteinases

Pemphigus VulgarisPemphigus Vulgaris

Pemphigus vulgarisPemphigus vulgaris

Bullous eruptions: skin and mucous membranesBullous eruptions: skin and mucous membranes

intraepithelialintraepithelial Oral mucosa is Oral mucosa is almost alwaysalmost always involved involved Fragile bullaeFragile bullae Any part of the oral mucosa may be involved, Any part of the oral mucosa may be involved,

soft palate, buccal mucosa and lipssoft palate, buccal mucosa and lips Desquamative gingivitis Desquamative gingivitis

Pemphigus VulgarisPemphigus Vulgaris Nikolsky sign Nikolsky sign


Direct immunofluorescence: Direct immunofluorescence: biopsy from biopsy from perilesional tissueperilesional tissue

Indirect immunoflourescenceIndirect immunoflourescence Disease monitoringDisease monitoring Autoantibodies to desmosomesAutoantibodies to desmosomes Titer correlates with severityTiter correlates with severity Not present in early stages? Or all patientsNot present in early stages? Or all patients


Histopathology Histopathology Intra epithelial Intra epithelial

separationseparation Little subepithelial Little subepithelial

inflammationinflammation Tzanck cellsTzanck cells

Other forms of pemphigus include:Other forms of pemphigus include: P. vegetansP. vegetans Drug inducedDrug induced paraneoplasticparaneoplastic

TREATMENT OF NON-MICROBIAL TREATMENT OF NON-MICROBIAL MUCOSITIS WITH CORTICOSTEROIDSMUCOSITIS WITH CORTICOSTEROIDS


MouthrinseMouthrinse Triamcinolone acetonideTriamcinolone acetonide

OintmentOintment Triamcinolone acetonideTriamcinolone acetonide Fluocinonide (Lidex)Fluocinonide (Lidex) ClobetasolClobetasol



Systemic SteroidsSystemic Steroids PrednisonePrednisone Contraindicated in certain systemic diseasesContraindicated in certain systemic diseases

Intralesional SteroidsIntralesional Steroids Triamcinolone acetonide, inject 10-40 mgTriamcinolone acetonide, inject 10-40 mg Anesthetize area before injection of steroidAnesthetize area before injection of steroid

Erythema MultiformeErythema Multiforme Wide range of clinical presentationWide range of clinical presentation Maculopapular, vesiculobullous, targetMaculopapular, vesiculobullous, target Orally:lips and anterior partsOrally:lips and anterior parts

Target

Erythema MultiformeErythema Multiforme Sudden onsetSudden onset Skin and mucous membranesSkin and mucous membranes

Pathogenesis is Pathogenesis is not clearnot clear Hypersensitivity rxn, type 3 hypersensitivityHypersensitivity rxn, type 3 hypersensitivity

And consequensesAnd consequenses

Ag - Ab complexes have been detected in EM and HSV infnAg - Ab complexes have been detected in EM and HSV infn

PrecipitatingPrecipitating factors include factors include Drugs: sulphonamides, penicillinsDrugs: sulphonamides, penicillins Viral infections: herpes simplex infectionViral infections: herpes simplex infection Spontaneously Spontaneously

Erythema MultiformeErythema Multiformeclinical featuresclinical features

Young adultsYoung adults Male >femaleMale >female Prodrome +,-Prodrome +,- RecurrentRecurrentSeverity varies:Severity varies: Oral lesions with or without skin lesionsOral lesions with or without skin lesions Skin lesions aloneSkin lesions alone

Subside in 10-14 daysSubside in 10-14 days Severe form: Severe form: Steven Johnson syndromeSteven Johnson syndrome: skin, : skin,

mucosal surfaces and conjunctival lesionsmucosal surfaces and conjunctival lesions

ERYTHEMA MULTIFORMEERYTHEMA MULTIFORMEERYTHEMA MULTIFORMEERYTHEMA MULTIFORME

Stevens-Johnson Syndrome:Stevens-Johnson Syndrome: A more severe form of erythema multiforme A more severe form of erythema multiforme Lesions involve skin, conjunctiva, oral Lesions involve skin, conjunctiva, oral

mucosa, genital mucosamucosa, genital mucosa

Erythema MultiformeErythema Multiforme

Microscopic features: Microscopic features: not diagnosticnot diagnostic Diagnosis is primarily Diagnosis is primarily clinicalclinical Treatment and prognosisTreatment and prognosis

Remove causative drugs, if anyRemove causative drugs, if any Topical and systemic corticosteroidsTopical and systemic corticosteroids May be recurrentMay be recurrent May benefit from prophylactic acyclovirMay benefit from prophylactic acyclovir

Erythema MultiformeErythema Multiforme

PemphigoidPemphigoid

Autimmune diseaseAutimmune disease Auto antibodies to Auto antibodies to hemihemidesmosomes and desmosomes and

basement membranebasement membrane

Separation is Separation is subepithelialsubepithelial Several different Ag are recognized Several different Ag are recognized

PemphigoidPemphigoid

2 clinical groups:2 clinical groups: Mucous membrane pemphigoidMucous membrane pemphigoid

Mainly mucosalMainly mucosal

Bullous pemphigoidBullous pemphigoid Mainly skinMainly skin

MUCOUS MEMBRANE MUCOUS MEMBRANE (CICATRICIAL) PEMPHIGOID(CICATRICIAL) PEMPHIGOID

MUCOUS MEMBRANE MUCOUS MEMBRANE (CICATRICIAL) PEMPHIGOID(CICATRICIAL) PEMPHIGOID

Etiology: antibodies against Etiology: antibodies against BP Ag2BP Ag2

Women>menWomen>men

Tense bullaeTense bullae

Oral Lesions of Mucous Oral Lesions of Mucous Membrane PemphigoidMembrane Pemphigoid

Heal with scarring (cicatritial)Heal with scarring (cicatritial)

90% involve gingiva, 90% involve gingiva, ““Chronic desquamative gingivitis” may Chronic desquamative gingivitis” may

be the only oral manifestationbe the only oral manifestation

Nikolsky signNikolsky sign

MMPMMP

Extraoral lesionsExtraoral lesions Conjunctiva: may cause blindnessConjunctiva: may cause blindness

Nasal, pharyngeal, vaginal mucosaNasal, pharyngeal, vaginal mucosa

SkinSkin

MMPMMP

Bullous PemphigoidBullous Pemphigoid

MUCOUS MEMBRANE PEMPHIGOID: MUCOUS MEMBRANE PEMPHIGOID: MICROSCOPICMICROSCOPIC

MUCOUS MEMBRANE PEMPHIGOID: MUCOUS MEMBRANE PEMPHIGOID: MICROSCOPICMICROSCOPIC

Subepithelial Subepithelial vesiclevesicle No subepithelial inflammation firstNo subepithelial inflammation first Later, inflammation and perivascular infiltrateLater, inflammation and perivascular infiltrate Eosinophils are involvedEosinophils are involved Release of proteasesRelease of proteases

MUCOUS MEMBRANE PEMPHIGOIDMUCOUS MEMBRANE PEMPHIGOID

Diagnosis: Diagnosis: Direct immunofluorescenceDirect immunofluorescence Indirect immunoF using modern Indirect immunoF using modern

techniquestechniques

ImmunofluorescenceImmunofluorescenceEssential for DiagnosisEssential for Diagnosis

MUCOUS MEMBRANE MUCOUS MEMBRANE PEMPHIGOIDPEMPHIGOID

Treatment: topical and/or systemic Treatment: topical and/or systemic corticosteroidscorticosteroids

Prognosis: good, but monitor eye lesionsPrognosis: good, but monitor eye lesions

Dermatitis HerpetiformisDermatitis Herpetiformis

Autoimmune diseaseAutoimmune disease Subepithelial Subepithelial blisteringblistering Primarly skin disease, oral manifestation Primarly skin disease, oral manifestation

variablevariable Small erythema to wide necrosisSmall erythema to wide necrosis

90% associated with gluten 90% associated with gluten hypersensitivityhypersensitivity

Dermatitis HerpetiformisDermatitis Herpetiformis

BiopsyBiopsy shows: shows: granular accumulation of granular accumulation of neutrophilsneutrophils

ImmunofluerescenceImmunofluerescence shows: shows:

IgAIgA deposition at the deposition at the tipstips of CT papilla of CT papilla

PathogenesisPathogenesis: activation of complement : activation of complement system and neutrophil chemotaxissystem and neutrophil chemotaxis

Linear IgA DiseaseLinear IgA Disease

Rare autoimmune disease of skin and Rare autoimmune disease of skin and occasionally oral.occasionally oral.

Histopathology: Histopathology: subepithelial seperationsubepithelial seperation D/D: dermatitis herpetiformis and MMPD/D: dermatitis herpetiformis and MMP Immunofluorescence: linear IGA along Immunofluorescence: linear IGA along

basement memnrane.basement memnrane. Gluten hypersensitivity in 30%Gluten hypersensitivity in 30%

Epidermolysis BullosaEpidermolysis Bullosa Complex group of syndromesComplex group of syndromes GeneGene mutations coding for keratins in mutations coding for keratins in

basal layer or collagensbasal layer or collagens

KeratinKeratin: intraepithelial bullae: intraepithelial bullae Basement membrane structureBasement membrane structure: :

subepithelial bullaesubepithelial bullae

TYPES OF EPIDERMOLYSIS TYPES OF EPIDERMOLYSIS BULLOSABULLOSA

TYPES OF EPIDERMOLYSIS TYPES OF EPIDERMOLYSIS BULLOSABULLOSA

SIMPLEX:SIMPLEX: localized skin lesions; oral lesions, localized skin lesions; oral lesions, good good prognosisprognosis

DYSTROPHIC DOMINANTDYSTROPHIC DOMINANT: nails; oral lesions; scarring; : nails; oral lesions; scarring; fair fair prognosisprognosis

DYSTROPHIC RECESSIVEDYSTROPHIC RECESSIVE: severe skin and oral : severe skin and oral lesions, scarring, abnormal teeth, lesions, scarring, abnormal teeth, poor poor prognosisprognosis

JUNCTIONAL: severe skin and oral lesions, abnormal JUNCTIONAL: severe skin and oral lesions, abnormal teeth, fatalteeth, fatal

Epidermolysis BullosaEpidermolysis Bullosa

Clinically: at birthClinically: at birth Extreme fragility of skinExtreme fragility of skin Heal slowly with scarringHeal slowly with scarring Several types are incompatible with lifeSeveral types are incompatible with life

Restricted mouth openingRestricted mouth openingRampant cariesRampant caries

EPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSA

TreatmentTreatment Avoid traumaAvoid trauma Antibiotics, corticosteroidsAntibiotics, corticosteroids PrognosisPrognosis

Simplex: goodSimplex: goodRecessive & Junctional: fatalRecessive & Junctional: fatal

Epidermolysis Bullosa AquisitaEpidermolysis Bullosa Aquisita

Autoimmune diseaseAutoimmune disease Linear deposition of IgG and C3 in the Linear deposition of IgG and C3 in the

basement membranebasement membrane zone zone

Angina Bullosa HaemorrhagicaAngina Bullosa Haemorrhagica(oral blood blister)(oral blood blister)

Spontaneous blood filled Spontaneous blood filled bullae bullae

Middle aged or elderlyMiddle aged or elderly Soft palate, solitarySoft palate, solitary Cause is unknown, Cause is unknown,

trauma?trauma? Histology: Histology: subepithelial subepithelial

seperationseperation Immunofluorescence: Immunofluorescence:

negativenegative

Erosive lichen planusErosive lichen planus

Differential diagnosis of Differential diagnosis of subepithelial blisteringsubepithelial blistering

PemphigoidPemphigoid Bullous lichen planusBullous lichen planus Linear IgA diseaseLinear IgA disease Dermatitis herpitiformisDermatitis herpitiformis Epidermolysis bullosa (both forms)Epidermolysis bullosa (both forms) Erythema multiformeErythema multiforme Angina bullosa hemorrhagicaAngina bullosa hemorrhagica

Differential diagnosis of Differential diagnosis of desquamative gingivitisdesquamative gingivitis

1. mucous membrane pemphigoid1. mucous membrane pemphigoid 2. pemphigus vulgaris2. pemphigus vulgaris 3. erosive lichen planus3. erosive lichen planus 4. allergic reaction4. allergic reaction 5. drug induced5. drug induced

oral ulceration and vesiculobullous diseases1and 2

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