Oral Ulceration and Vesiculobullous Diseases

Dr. Rima Safadi 2010

Ulcer Definition:
Localized defect in the surface epithelium exposing an inflamed connective tissue base  Most common lesion of the oral mucosa  May be a manifestation of many disease entities Erosion: is a superficial ulcer

Causes of oral ulceration
Infective Traumatic Idiopathic Associated with systemic diseases Associated with dermatologic diseases Neoplastic Keep them in mind when thinking of D/D of an ulcer

Traumatic Ulceration
Mechanical Chemical Thermal Factitious Radiation Eosinophilic ulcer (traumatic granuloma)

Mechanical Ulceration
 Three criteria for diagnosis
1. Define a cause 2. Fit size, shape and location of ulcer 3. Healing within 10 days of cause removal

 Chronic ulcers may look like neoplasms
 Deep crater like ulcer with rolled everted margins and induration

 When is biopsy indicated?

Chronic Traumatic Ulcer

Chemical Ulceration
 Materials used in dental practice  Self treatment of oral complaints, the use
of aspirin, undiluted mouth washes  Reaction varies in severity: edema to necrosis

Aspirin burn

Chemical burn

Hydrogen peroxide burn

Formocresol burn

Anesthetic necrosis

Thermal Ulcerations
 Hot food or drink

Factitious ulcers

Factitious ulcers

 Damage to the epithelium  Damage to blood vessels: atrophic and necrotic
epithelium  Damage to lymphatics: edema

 Thin atrophic epithelium prone to traumatic

 Differentiate radiation ulcers (painful) from
neoplastic ulcers


RAD mucositis

Eosinophic ulcer (traumatic ulcerative granuloma)
 Etiology: trauma and
crush to muscles

 Clinical appearance

 Histopathologic features
 Sheets of histiocytes and some eosinophils

 No relation to eosinophilic
granuloma of bone  treatment

Recurrent aphthous stomatitis
 “idiopathic” or immune
mediated  Frequent recurrences

 3 types: minor major and

 Clinical features:
 Prodromal symptoms 1-2 days before  Tingling sensation  Red macule

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

Minor aphthous ulceration
 80% of RAS  Affect non keratinized    
mucosa 1-5 in no Less than 10 mm No scarring Recur in 1-4 months

Minor RAS

Major aphthous ulceration
 Larger >10 mm  Location: any where in  
the mouth Number 1-10 Healing duration 4-6 weeks Nature: with scar Recur in less than 1 month Deeper with rolled margins D/D of OSCC

 

Major RAS-scarring

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

Etiology of RAS
 Most likely immune mediated Box 12.1  Co factors

Etiology of RAS (pathogenesis)
 Immune mediated cytotoxic damage to
oral epithelium  Cross reactivity between bacterial products (streptococcal) and epithelial antigens (HSP)  T cell mediated cytotoxicity
 CD4 + predominate the pre ulcerative phase  CD8+ cytotoxic predominate ulcerative phase

Etiology of RAS associated factors
 Hereditary predisposition
 45% has family history

 Trauma
 May influence the site

 Emotional stress
 Precipitating factor  Biting of the mucosa

 Cigarette smoking, reverse relation

Etiology of RAS associated factors
 Infective agents?
 Hypersensitivity to Strep sanguis??? or cross reactivity?  Adenovirus?  Varicella-zoster and CMV??  Rise of IgM at times of recurrences

RAS associated factors
 Allergic disorders:
 Food allergy  The presence of raised IgE

 Hematological disorders
 In 20% of patients:  Iron, folic acid, B12 deficiency, Causal role?

 Gastrointestinal diseases,
 Celiac disease (gluten hypersensitivity)  2-4%  Minor type  Ulcerative colitis and Crohn`s disease

Etiology of RAS associated factors
 Hormonal disturbance:
 Puberty, menstruation  Pregnancy?  No consistent association

 Infiltration by lymphocytes  Damage to the epithelium and more
infiltration  Decrease in lymphocytes upon healing  Epithelial infiltrate is T cell cytotoxic followed by CD4 in healing phase

Behcet disease (syndrome)
 RAS and at least 2 of the following
    Genital ulcers Eye lesions Skin lesions Pathergy test: rapid inflammation due to minor trauma

 Genetic predisposition
 HLA- B51

 Immune mediated mucosal damage  Vasculitis
 Hyper reactivity of PMN

Vesiculbullous diseases
 Meaning of the name  Collection of clear fluid within or below the
epithelium  Classification:
 Intraepithelial  Subepithelial

 Intraepithelial vesiculobullous:
 Acantholytic: pemphigus, breakdown of intercellular attachment  Non acantholytic: herpetic infection, death of cells

Vesiculbullous diseases
 History is important
 duration, recurrence  skin, eye, genital lesions  medications, systemic manifestations

 Vulgaris is the most common type  Female more than male  Ethnic groups: Ashkenazi Jews

 Autoimmue: auto antibodies against
epithelial desmosomes

 Pathogenesis: auto Ab against
 Desmoglein 3  Desmoglein 1 and 3 in skin and oral  Activation of proteinases

Pemphigus Vulgaris

Pemphigus Vulgaris

Pemphigus vulgaris
 Bullous eruptions: skin and mucous membranes  intraepithelial  Oral mucosa is almost always involved  Fragile bullae  Any part of the oral mucosa may be involved,
soft palate, buccal mucosa and lips
 Desquamative gingivitis

Pemphigus Vulgaris Nikolsky sign

Pemphigus vulgaris
 Direct immunofluorescence:
 biopsy from perilesional tissue

 Indirect immunoflourescence
    Disease monitoring Autoantibodies to desmosomes Titer correlates with severity Not present in early stages? Or all patients

Pemphigus Vulgaris

Pemphigus vulgaris
Histopathology  Intra epithelial separation  Little subepithelial inflammation  Tzanck cells

Pemphigus Vulgaris

 Other forms of pemphigus include:  P. vegetans  Drug induced  paraneoplastic


 Mouthrinse
 Triamcinolone acetonide

 Ointment
 Triamcinolone acetonide  Fluocinonide (Lidex)  Clobetasol


 Systemic Steroids
 Prednisone  Contraindicated in certain systemic diseases

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

Erythema Multiforme
 Wide range of clinical presentation  Maculopapular, vesiculobullous, target  Orally:lips and anterior parts


Erythema Multiforme
 Sudden onset  Skin and mucous membranes
 Pathogenesis is not clear
 Hypersensitivity rxn, type 3 hypersensitivity  And consequenses
 Ag - Ab complexes have been detected in EM and HSV infn

 Precipitating factors include
 Drugs: sulphonamides, penicillins  Viral infections: herpes simplex infection  Spontaneously

Erythema Multiforme clinical features
   
Young adults Male >female Prodrome +,Recurrent Severity varies:  Oral lesions with or without skin lesions  Skin lesions alone

 Severe form: Steven Johnson syndrome: skin,
mucosal surfaces and conjunctival lesions

 Subside in 10-14 days

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

Erythema Multiforme
 Microscopic features: not diagnostic  Diagnosis is primarily clinical  Treatment and prognosis
    Remove causative drugs, if any Topical and systemic corticosteroids May be recurrent May benefit from prophylactic acyclovir

Erythema Multiforme

 Autimmune disease
 Auto antibodies to hemidesmosomes and basement membrane

 Separation is subepithelial  Several different Ag are recognized

 2 clinical groups:  Mucous membrane pemphigoid
 Mainly mucosal

 Bullous pemphigoid
 Mainly skin

 Etiology: antibodies against BP Ag2  Women>men  Tense bullae

Oral Lesions of Mucous Membrane Pemphigoid
 Heal with scarring (cicatritial)
 90% involve gingiva,
 “Chronic desquamative gingivitis” may be the only oral manifestation

 Nikolsky sign



 Extraoral lesions
 Conjunctiva: may cause blindness  Nasal, pharyngeal, vaginal mucosa  Skin


Bullous Pemphigoid


 Subepithelial vesicle
    No subepithelial inflammation first Later, inflammation and perivascular infiltrate Eosinophils are involved Release of proteases

Diagnosis:  Direct immunofluorescence  Indirect immunoF using modern techniques

Immunofluorescence Essential for Diagnosis

 Treatment: topical and/or systemic
corticosteroids  Prognosis: good, but monitor eye lesions

Dermatitis Herpetiformis
 Autoimmune disease  Subepithelial blistering  Primarly skin disease, oral manifestation
 Small erythema to wide necrosis

 90% associated with gluten

Dermatitis Herpetiformis
 Biopsy shows: granular accumulation of

 Immunofluerescence shows:
IgA deposition at the tips of CT papilla

 Pathogenesis: activation of complement
system and neutrophil chemotaxis

Linear IgA Disease
 Rare autoimmune disease of skin and
occasionally oral.

 Histopathology: subepithelial seperation  D/D: dermatitis herpetiformis and MMP  Immunofluorescence: linear IGA along
basement memnrane.  Gluten hypersensitivity in 30%

Epidermolysis Bullosa
 Complex group of syndromes  Gene mutations coding for keratins in
basal layer or collagens  Keratin: intraepithelial bullae  Basement membrane structure: subepithelial bullae

 SIMPLEX: localized skin lesions; oral lesions,
good prognosis

 DYSTROPHIC DOMINANT: nails; oral lesions;
scarring; fair prognosis

 DYSTROPHIC RECESSIVE: severe skin and
oral lesions, scarring, abnormal teeth, poor prognosis

 JUNCTIONAL: severe skin and oral lesions,

Epidermolysis Bullosa
 Clinically: at birth  Extreme fragility of skin  Heal slowly with scarring  Several types are incompatible with life

Restricted mouth opening Rampant caries

 Treatment
 Avoid trauma  Antibiotics, corticosteroids  Prognosis  Simplex: good  Recessive & Junctional: fatal

Epidermolysis Bullosa Aquisita
 Autoimmune disease  Linear deposition of IgG and C3 in the
basement membrane zone

Angina Bullosa Haemorrhagica (oral blood blister)
 Spontaneous blood filled

  
 

bullae Middle aged or elderly Soft palate, solitary Cause is unknown, trauma? Histology: subepithelial seperation Immunofluorescence: negative

Erosive lichen planus

Differential diagnosis of subepithelial blistering
 Pemphigoid  Bullous lichen planus  Linear IgA disease  Dermatitis herpitiformis  Epidermolysis bullosa (both forms)  Erythema multiforme  Angina bullosa hemorrhagica

Differential diagnosis of desquamative gingivitis
 1. mucous membrane pemphigoid  2. pemphigus vulgaris  3. erosive lichen planus  4. allergic reaction  5. drug induced

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