Oral Ulceration and Vesiculobullous Diseases1and 2
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Transcript of Oral Ulceration and Vesiculobullous Diseases1and 2
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Oral Ulceration and Oral Ulceration and Vesiculobullous DiseasesVesiculobullous Diseases
Dr. Rima SafadiDr. Rima Safadi
20102010
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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
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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
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Traumatic Ulceration Traumatic Ulceration
MechanicalMechanical
ChemicalChemical
ThermalThermal
FactitiousFactitious
RadiationRadiation
Eosinophilic ulcer (traumatic granuloma)Eosinophilic ulcer (traumatic granuloma)
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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?
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Chronic Traumatic UlcerChronic Traumatic Ulcer
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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
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Aspirin burnAspirin burn
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Chemical burnChemical burn
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Hydrogen peroxide burnHydrogen peroxide burn
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Formocresol burnFormocresol burn
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Anesthetic necrosisAnesthetic necrosis
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Thermal UlcerationsThermal Ulcerations
Hot food or drinkHot food or drink
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Factitious ulcersFactitious ulcers
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Factitious ulcersFactitious ulcers
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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
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SCC
RAD mucositis
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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
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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
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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
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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
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Minor RASMinor RAS
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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
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Major RAS-scarringMajor RAS-scarring
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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
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Etiology of RASEtiology of RAS
Most likely immune mediated Box 12.1Most likely immune mediated Box 12.1 Co factorsCo factors
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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
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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
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Etiology of RASEtiology of RASassociated factorsassociated factors
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
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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
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Etiology of RASEtiology of RASassociated factorsassociated factors
Hormonal disturbance:Hormonal disturbance: Puberty, menstruationPuberty, menstruation Pregnancy?Pregnancy?
No consistent associationNo consistent association
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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
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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
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Pathogenesis Pathogenesis
Genetic predispositionGenetic predisposition HLA- B51HLA- B51
Immune mediated mucosal damageImmune mediated mucosal damage
VasculitisVasculitis Hyper reactivity of PMNHyper reactivity of PMN
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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
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Vesiculbullous diseasesVesiculbullous diseases
History is importantHistory is important duration, recurrenceduration, recurrence skin, eye, genital lesionsskin, eye, genital lesions medications, systemic manifestationsmedications, systemic manifestations
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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
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PemphigusPemphigus Autoimmue: auto antibodies against Autoimmue: auto antibodies against
epithelial desmosomesepithelial desmosomes
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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
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Pemphigus VulgarisPemphigus Vulgaris
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Pemphigus VulgarisPemphigus Vulgaris
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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
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Pemphigus VulgarisPemphigus Vulgaris Nikolsky sign Nikolsky sign
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Pemphigus vulgarisPemphigus vulgaris
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
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Pemphigus VulgarisPemphigus Vulgaris
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Pemphigus vulgarisPemphigus vulgaris
Histopathology Histopathology Intra epithelial Intra epithelial
separationseparation Little subepithelial Little subepithelial
inflammationinflammation Tzanck cellsTzanck cells
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Pemphigus VulgarisPemphigus Vulgaris
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Other forms of pemphigus include:Other forms of pemphigus include: P. vegetansP. vegetans Drug inducedDrug induced paraneoplasticparaneoplastic
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TREATMENT OF NON-MICROBIAL TREATMENT OF NON-MICROBIAL MUCOSITIS WITH CORTICOSTEROIDSMUCOSITIS WITH CORTICOSTEROIDS
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
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TREATMENT OF NON-MICROBIAL TREATMENT OF NON-MICROBIAL MUCOSITIS WITH CORTICOSTEROIDSMUCOSITIS WITH CORTICOSTEROIDS
TREATMENT OF NON-MICROBIAL TREATMENT OF NON-MICROBIAL MUCOSITIS WITH CORTICOSTEROIDSMUCOSITIS WITH CORTICOSTEROIDS
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
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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
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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
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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
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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
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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
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Erythema MultiformeErythema Multiforme
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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
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PemphigoidPemphigoid
2 clinical groups:2 clinical groups: Mucous membrane pemphigoidMucous membrane pemphigoid
Mainly mucosalMainly mucosal
Bullous pemphigoidBullous pemphigoid Mainly skinMainly skin
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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
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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
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MMPMMP
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MMPMMP
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Extraoral lesionsExtraoral lesions Conjunctiva: may cause blindnessConjunctiva: may cause blindness
Nasal, pharyngeal, vaginal mucosaNasal, pharyngeal, vaginal mucosa
SkinSkin
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MMPMMP
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Bullous PemphigoidBullous Pemphigoid
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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
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MUCOUS MEMBRANE PEMPHIGOIDMUCOUS MEMBRANE PEMPHIGOID
Diagnosis: Diagnosis: Direct immunofluorescenceDirect immunofluorescence Indirect immunoF using modern Indirect immunoF using modern
techniquestechniques
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ImmunofluorescenceImmunofluorescenceEssential for DiagnosisEssential for Diagnosis
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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
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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
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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
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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%
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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
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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
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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
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Restricted mouth openingRestricted mouth openingRampant cariesRampant caries
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EPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSA
TreatmentTreatment Avoid traumaAvoid trauma Antibiotics, corticosteroidsAntibiotics, corticosteroids PrognosisPrognosis
Simplex: goodSimplex: goodRecessive & Junctional: fatalRecessive & Junctional: fatal
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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
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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
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Erosive lichen planusErosive lichen planus
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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
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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
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