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

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

Thin atrophic epithelium prone to traumatic

ulcers

Differentiate radiation ulcers (painful) from

neoplastic ulcers

SCC

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

herpetiform

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

Histopathology
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

Pathogenesis
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

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

Pemphigus
Autoimmue: auto antibodies against
epithelial desmosomes

Pemphigus
Pathogenesis: auto Ab against
desmosomes
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

TREATMENT OF NON-MICROBIAL MUCOSITIS WITH CORTICOSTEROIDS

Mouthrinse
Triamcinolone acetonide

Ointment
Triamcinolone acetonide Fluocinonide (Lidex) Clobetasol

TREATMENT OF NON-MICROBIAL MUCOSITIS WITH CORTICOSTEROIDS

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

Target

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

ERYTHEMA MULTIFORME
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

Pemphigoid
Autimmune disease
Auto antibodies to hemidesmosomes and basement membrane

Separation is subepithelial Several different Ag are recognized

Pemphigoid
2 clinical groups: Mucous membrane pemphigoid
Mainly mucosal

Bullous pemphigoid
Mainly skin

MUCOUS MEMBRANE (CICATRICIAL) PEMPHIGOID

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

MMP

MMP

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

MMP

Bullous Pemphigoid

MUCOUS MEMBRANE PEMPHIGOID: MICROSCOPIC

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

MUCOUS MEMBRANE PEMPHIGOID

Diagnosis: Direct immunofluorescence Indirect immunoF using modern techniques

Immunofluorescence Essential for Diagnosis

MUCOUS MEMBRANE PEMPHIGOID

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

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

90% associated with gluten

hypersensitivity

Dermatitis Herpetiformis
Biopsy shows: granular accumulation of
neutrophils

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

TYPES OF EPIDERMOLYSIS BULLOSA

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

EPIDERMOLYSIS BULLOSA
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