Oral Vesicular Bullous

disorders

ORAL BLISTERING DISORDERS

 Definitions

• Blister: Accumulation of fluid either within or below

the epidermis and mucous membrane

• Vesicle: Elevated blister containing clear fluid that is

lesser than 1 cm in diameter

• Bulla: Elevated blister containing clear fluid that is

greater than 1 cm in diameter
 Ulcer: A lesion of the skin or of a mucous membrane,
that is accompanied by formation of pus and
necrosis of surrounding tissue, usually resulting from
inflammation or ischemia

 A break in skin or mucous membrane with loss of

surface tissue, disintegration and necrosis of
epithelial tissue, and often pus
 Mechanisms of blistering

 Inherited mutational defects of basement

membrane proteins
 Autoantibodies
 Cellular immune mediated disorders
 Metabolic disturbance
 Subepidermal edema
 Acute inflammatory process
 Classification - Oral blistering lesions

According to clinical course:

o Acute lesions:
 Primary herpetic gingivostomatitis
 Herpes zoster
 Erythema multiforme
o Chronic lesions:
 Pemphigus
 Bullous pemhigoid
 Bullous lichen planus
According to etiology:
o Hereditary/Inherited disorders:
 Epidermolysis bullosa
 Dyskeratosis congenita
 Familial benign chronic pemphigus
o Autoimmune/Immunological/immune mediated
disorders:
• Erythema multiforme
• Pemphigus
• Bullous pemphigoid
• Bullous lichen planus
• Cicatricial pemphigoid
• Linear IgA disease
• Dermatitis herpeteformis
o Infectious disorders:

 Bacterial infections:
 Congenital syphilis

 Fungal infections:
 Id reaction
 Viral infections:
 Primary herpetic gingivostomatitis
 Herpes zoster/ Chicken pox
 Herpangina
 Hand, Foot and Mouth disease
o Miscellaneous:
 Allergic stomatitis
 Oral submucous fibrosis
 Burns and scalds
According to histology:
o Intraepithelial/ Suprabasal lesions:
 Pemphigus
 Familial benign chronic pemphigus
 Primary herpetic gingivostomatitis
 Herpes zoster
 Herpangina
o Subepithelial lesions:
 Bullous pemphigoid
 Cicatricial pemphigoid
 Bullous lichen planus
 Linear IgA disease
 Bullous systemic lupus erythematosus
 Angina bullosa hemorrhagica
 Epidermolysis bullosa acquisita
 Chronic bullous disease of childhood
o Both intraepithelial & subepithelial:
 Erythema multiforme
 Epidermolysis bullosa
 Paraneoplastic pemphigus
 Classification – Oral ulcerative lesions

According to clinical course:

o Acute lesions:
• ANUG
• Aphthous ulcers
• Herpetic gingivostomatitis
o Chronic lesions:
• Malignant ulcer
• Traumatic ulcer
• Tuberculous ulcer

o Recurrent lesions:
• Aphthous ulcers
• RHL/RIH
• Cyclic neutropenia
• Behcet’s syndrome
According to onset:
o Primary lesions:
• Traumatic ulcers
• Malignant ulcers
• Tuberculous ulcers
o Secondary lesions:
• Herpes zoster
• AHGS/ RHL/RIH
• Pemphigus
According to number:
o Solitary ulcers:
• Traumatic ulcers
• Malignant ulcers
• Tuberculous ulcers
• Deep fungal ulcers
o Multiple ulcers:
• AHGS/ RHL/RIH
• Aphthous ulcers
• Pemphigus
• Erythema multiforme
According to etiology:
o Traumatic ulcers:
 Physical
• TUGSE
• Traumatic ulcer
 Chemical
• Chemical burn
• Aspirin burn
 Thermal
• Pizza burn
• Electric burns
o Infectious ulcers:
 Bacterial
 Tuberculous ulcer
 Syphilitic ulcer
 Leprosy
 ANUG
 Viral ulcers
• AHGS/ RHL
• Herpes zoster
• Herpangina
• Hand, foot & mouth disease
 Fungal ulcers
• Candidiasis
• Mucormycosis
• Histoplasmosis
• Cryptococcosis
• Blastomycosis
o Autoimmune/ Immune mediated:
• Pemhigus
• Pemphigoid
• Erythema multiforme
• Lichen planus
• Discoid lupus erythematosus
o Nutritional deficiencies:
• Vitamin B complex
• Iron

o Hematologic disorders:
• Leukemia
• Agranulocytosis
• Neutropenia/ cyclic
o Neoplastic ulcers:
• Squamous cell carcinoma
• Adenoid cystic/ adenocarcinoma
• Mucoepidermoid carcinoma
• Melanoma
• lymphoma
o Preneoplastic ulcers:
• Lichen planus
• Oral submucous fibrosis
• Discoid lupus erythematosus

o Miscellaneous
• Allergic stomatitis
 Primary herpetic gingivostomatitis

 Incubation period: 2-12 days

 Prodromal symptoms: fever, malaise, headache,
nausea, vomiting
 Vesicles, thin-walled, surrounded by an
inflammatory base, rupture quickly, shallow, round,
discrete ulcers
 Generalized, acute desquamative gingivitis
 Lymphadenitis
 Diagnosis

 Cytology- Tzanck smear: multinucleated giant cells,

ballooning degeneration of nucleus
 Biopsy
 Serology: rising antibody titer
 Viral isolation- culture, PCR
 Immunpmorphological tests: direct fluorescent
assay, indirect immunofluorescence
 Treatment

 Self limiting
 Rest, fluid, electrolyte balance
 Antipyeretics
 Topical anesthetic: dyclonine HCL 0.5%,
diphenhydramine HCL 5mg/ml,
 Antiviral drugs: Acyclovir- 15mg/kg, Valacyclovir,
Famciclovir
 Recurrent herpes labialis

 Cold sore, Fever blister

 Predisposing factors: trauma, fever, stress,
menstruation, immunosuppression,sunburn, cold
 Tingling and burning, vesicles, clusters
 Recurrent intraoral herpes

 Vesicles, clusters
 keratinised mucosa
 Ulcers
 Diagnosis

 Cytology

 Viral isolation
 Treatment

 Acyclovir, Valacyclovir
 Famciclovir, Penciclovir
 Docosanol
 Herpangina

 Coxsackie A4
 Incubation period: fever, malaise
 Sore throat, dysphagia
 Vesicles, rupture into ulcers
 Occurs in epidemics
 Milder
 Pharynx, posterior oral cavity
 Gingivitis absent
 Smaller lesions
 Diagnosis / treatment

 Cytology
 Self limiting
 Rest, fluid, electrolyte balance
 Topical anesthetics
 Hand, foot and mouth disease

 Coxsackie A 16
 Fever, macules, papules, vesicles- hands and feet
 Oral vesicles, ulcers
 CNS involvement, myocarditis, pulmonary edema
 Treatment: supportive
 Herpes zoster

• Varicella Zoster virus- reactivation

• Oral lesions: Trigeminal N- branches 2, 3
• Prodromal symptoms: shooting pain, burning
sensation
• Vesicles, rupture into ulcers
• Unilateral
• Pulpal necrosis, internal root resorption
• Osteonecrosis, exfoliation of teeth
 Post herpetic neuralgia

 Pain persisting for over a month after the

mucocutaneous lesions have healed

 > 60 years of age, < cell mediated immunity

 Pain, paresthesia, hyperesthesia, sensory deficit

 Ramsay Hunt syndrome

 Herpes zoster of geniculate ganglion

 Bell’s palsy, unilateral vesicles of external ear, oral
vesicles, loss of taste sensation
 Tinnitus, vertigo, hearing deficits
 Diagnosis

 Cytology- Tzanck smear

 Serology: rising antibody titer
 Viral isolation
 Treatment

 Acyclovir- 800mg 5 /day, Valacyclovir, Famciclovir

 Corticosteroids?
 Intralesional steroids+ local anesthetics
 Topical capsaicin
 Tricyclic antidepressants, Gabapentin
 Chemical/surgical neurolysis
DISEASE CLINICAL FEATURES CAUSE SIGNIFICANCE

Primary Multiple painful oral Herpes Self –limited, heals

herpetic ulcers preceded by simplex virus in about 2 weeks,
gingivost vesicles; may have type 1 reactivation of
omatitis similar perioral and (occasionally latent virus results
skin lesions, fever and type 2) in secondary
gingivitis is usually infections;
present; usually affects circulating
children below 5 years antibodies provide
of age only partial
immunity
DISEASE CLINICAL FEATURES CAUSE SIGNIFICANCE
Secondary Multiple small ulcers Herpes simplex Self –limited, heals in
herpes preceded by vesicle; virus - about 2 weeks, without
simplex prodromal represents scar; lesions infectious
infection symptoms of reactivation of during vesicular stage,
tingling; burning or latent virus and patient must be
pain; most common not reinfection; cautioned against
on lip; intraorally on commonly autoinoculation;
palate and attached precipitated by herpes type 1
gingiva; adults and stress, sunlight, infections have not
young adults usually cold been linked
affected; very temperature, convincingly to oral
common; called low resistance cancer; any site
herpetic whitlow and affected in AIDS
when occurs on immunodeficien patients
fingers cy
DISEASE CLINICAL FEATURES CAUSE SIGNIFICANCE
Varicella Painful pruritic Varicella zoster Self –limited, recovery
vesicles and ulcers in virus uneventful in several
all stages on trunk weeks
and face; few oral
lesions; common
childhood disease

Herpes Unilateral multiple Varicella zoster Self-limited, but may

Zoster ulcers preceded by virus- have a prolonged,
vesicles distributed Reactivation of painful course; seen in
along a sensory latent virus debilitation, trauma,
nerve course; very neoplasia and
painful; usually on immunodeficiency
trunk, head and
neck; rare intraorally;
adults
DISEASE CLINICAL FEATURES CAUSE SIGNIFICANCE
Hand – foot Painful ulcers Coxsackie Self –limited, recovery
– mouth preceded by vesicle viruses uneventful in about 2
disease on hands, feet and weeks
oral mucosa;
usually children;
rare

Herpangina Multiple painful Coxsackie Self –limited, recovery

ulcers in posterior viruses uneventful in less than
oral cavity and a week
pharynx; lesions
preceded by
vesicles; children
most commonly
affected; seasonal
occurrence; rare
 ID reaction

 Also called Monilids

 Secondary skin response to candida infection
characterized by a localised or generalised sterile
vesiculopapular rash
 An allergic response to Candida antigens
 Resolves with treatment of candidiasis
 Patches of erythema periorally with oral
candidiasis
 Erythema multiforme

Acute, self limiting, inflammatory mucocutaneous

disease
Types:
 Minor- < 10% skin involvement, minimal or no
mucosal involvement
 Major – extensive skin involvement, mucosal
involvement
 Recurrent
 Chronic
Variants:
 Steven Johnson syndrome
 Toxic epidermal necrolysis
Etiology:
 Hypersensitivity reaction
 An immune mediated disease- deposition of immune
complexes in the superficial microvasculature of skin
& mucosa
 Idiopathic- no obvious detectable cause
Predisposing factors:
• Infections:
• Viral -Herpes simplex infection
• Bacterial- Tuberculosis, Mycoplasma pneumoniae
• Fungal- Histoplasmosis
• Protozoal infections
• Drugs: NSAID’s, anticonvulsants, sulfonamides,
barbiturates, penicillin, salicylates, carbamazepine,
antiretrovirals, lamotrigine, azithromycin
 Benign, malignant tumors
 Radiotherapy
 Crohn’s disease, sarcoidosis
 Stress, emotional factors
 Clinical features:

Clinical features:
 Children & young adults-20- 40 years, men
 Acute, explosive onset
 Prodromal symptoms- fever, malaise, headache, sore
throat, rhinorrhoea, cough
 Skin lesions- macules, papules, vesicles, bullae
extremities, face, neck, elbows, knees
 “Typical Target/Iris lesions”- central blister, necrosis
surrounded by edema and concentric rings of
erythema
 “Atypical target lesions”
 Oral findings:

45%
• Erythema, erosions, bullae, ulcerations, extensive
areas of inflammation, denudation
• Lips, buccal mucosa, tongue, labial mucosa
• Difficulty eating, drinking, swallowing
• Drooling blood tinged saliva
• Hemorrhagic crusting of lips
• May be the sole manifestation of the disease
Stevens Johnson syndrome (SJS)/ Toxic epidermal
necrolysis (TEN):
 Medications, mycoplasma pneumoniae
 Severe lesions- erosions, bullae, ulcers, crusted lips
 Chest> extremities- “atypical targets”
 Eyes, genitalia, mouth, skin
 Extensive oral ulceration with hemorrhagic crusting
of lip
 TEN more severe variant of SJS- sloughing of skin &
mucosa in large sheets, older people, females
 Secondary infection, fluid & electrolyte imbalance,
involvement of lungs, liver, kidneys
Differential diagnosis:
 Primary herpetic gingivostomatitis
 Pemphigus
 Paraneoplastic pemphigus
 Pemphigoid
 Aphthous stomatitis
Diagnosis:
 History
 Clinical findings
 Biopsy
Management:
Self limiting
 Mild- supportive ie topical anesthetics, soft, liquid
diet, rehydration

 Moderate/severe- systemic corticosteroids

30-50 mg/d prednisone, methylprednisolone

 Prophylactic Acyclovir- 400mg BID, Valacyclovir-
500mg BID

 Azathioprine, Dapsone- 100-150 mg/d

 SJS/TEN- burn centers- removal of necrotic skin

with grafting
 Pemphigus

 Autoimmune, chronic, life threatening

mucocutaneous diesease
Types:
 Pemphigus vulgaris
 Pemphigus vegetans
 Pemphigus erythematosus
 Pemphigus foliaceous
 Paraneoplastic pemphigus
 Drug related pemphigus
Etiology:
 Autoantibodies directed against intercellular
cementing substance (epidermal cell surface
glycoproteins- desmoglein 1 & 3)

 Loss of cell adherence

 Split develops within the epitelium- blister formation

Clinical features:
 Adults- 50-60 years, no sex predilection
 Pemphigus vulgaris most common- 80%
 Thin walled bullae- break rapidly
 Extend peripherally- large denuded areas of skin,
mucosa
 Nikolsky’s sign- positive
 Asboe Hansen sign- positive
Upper layer of the skin, mucosa pulling away from the
basal layer
Oral findings:
 90% affected, in 60% - first sign of the disease
 Buccal mucosa, palate, gingiva, tongue
 Bulla on a non inflamed base- rapidly break
 Shallow, irregular, large ulcers- edges extend
peripherally- large denuded areas involving most
of the mucosa, co existing candidiasis
 Desquamative gingivitis-sole manifestation
Differential diagnosis:
 Primary herpetic gingivostomatitis
 Erythema multiforme
 Pemphigoid
 Lichen planus
 Aphthous stomatitis
Diagnosis:
 History
 Clinical findings
 Cytology-Tzanck smear- acantholytic cells
 Biopsy- intraepithelial split
 Immunofluorescence
Direct- positive, intercellular
Indirect- positive, circulating autoantibodies
Management:
 Corticosteroids- systemic, topical
1-2 mg/kg/d
 Steroid sparing drugs- cyclosporine,
cyclophosphamide, azathioprine
 Parenteral gold therapy, dapsone, etretinate,
chlorambucil, levamisol, methotrexate
 Plasmapheresis
 PUVA therapy
 Paraneoplastic pemphigus

Severe variant, associated with an underlying

neoplasm-
 Non -Hodgkin’s lymphoma
 Chronic lymphocytic leukemia
 Thymoma
 Castleman disease
 Waldenstrom macroglobulinemia
 Clinical features

 Adults- 60-70 years, both sexes

 Severe, rapid blistering of skin, mucosa
 Pulmonary involvement, conjunctiva, vagina

 Oral lesions- common

 Large, necrotic, painful, inflamed lesions on lips,
tongue, soft palate
 Diagnosis/ Management

• History
• Clinical features
• Biopsy

• Treat underlying disease

• Corticosteroids+ azathioprine, methotrexate,
cyclophosphamide
• Fatal
 Drug induced pemphigus

 Penicillamine, penicillin, phenobarbital, ACE

inhibitors- captopril, NSAID’s

 Discontinuation of drug- spontaneous recovery

 Subepithelial bullous dermatoses

Group of autoimmune, blistering disorders

characterized by a weakened basement membrane
 Bullous pemphigoid
 Mucous membrane pemphigoid
 Linear IgA disease
 Epidermolysis bullosa aquisita
 Chronic bullous disease of childhood
 Bullous pemphigoid
Etiology

A chronic, autoimmune disorder

Caused by binding of autoantibodies to antigens (BP
antigens- BP 180 & BP 230) in the lamina lucida of
the basement membrane on the hemidesmosomes of
epithelial basal cells- damage to basement
membrane- subepithelial vesicle formation
Can occur in association with
 Multiple sclerosis
 Malignancy
 Drug therapy- diuretics
 Clinical features

 Adults, > 60 years

 Macules, papules
 Blister on an inflamed base- scalp, arms, legs, axilla,
groin
 Do not extend at the periphery
 Pruritis
 Self limiting
 Oral findings

 30- 50 %
 Vesicles, bullae- small, form slowly, less painful
 Desquamative gingivitis
 Differential diagnosis

 Pemphigus
 Mucous membrane pemphigoid
 Lichen planus- bullous, erosive
 Diagnosis

 History
 Clinical features
 Biopsy
 Immunofluorescence
Direct- positive, basement membrane
Indirect- not reliable
 Management

 Corticosteroids – systemic, topical

 Steroid sparing agents- azathioprine,

cyclophosphamide, mycophenolate

 Dapsone, tetracycline, doxycycline, minocycline +

niacinamide
 Mucous membrane pemphigoid
Cicatricial pemphigoid

A chronic, autoimmune disorder

Autoantibodies directed against basement membrane-

subepithelial vesicle formation

Primarily affects mucous membrane

Association with underlying malignancy?

 Clinical features

 Adults, > 50 years

 Women> men
 Any mucosa, oral mucosa, conjunctiva, laryngeal,
genital, oesophagal, skin
 Oral findings

 90%
 Desquamative gingivitis
 Vesicles, bullae- intact
 Erosions, ulcerations
 Spread slowly, self limiting
 Diagnosis

 History
 Clinical features
 Biopsy
 Immunofluorescence
Direct- positive, basement membrane
 Management

 Corticosteroids- topical, intralesional, systemic

 Soft splint covering gingiva to hold medicament
 Tetracycline, doxycycline, minocycline
 Dapsone , immunosuppressants
 Linear IgA disease
Etiology

 Unknown
 Drug induced
 Associated with hematologic malignancies,
dermatmyositis
 Clinical features

 Pruritic papules and blisters- skin, elbows, knees

 Oral mucosa, conjunctiva
 Oral findings

 70%
 Similar to MMP
 Vesicles, bullae, erosins, ulcerations of oral mucosa
 Desquamative gingivitis
 Diagnosis

 History
 Clinical features
 Biopsy
 Immunofluorescence
Direct- positive, basement membrane (IgA)
Indirect- usually negative
 Management

 Corticosteroids- topical, systemic

 Dapsone, sulfapyridine, tetracycline+ niacinamide
 Immunosuppressants
Epidermolysis bullosa aquisita
Chronic bullous disease of childhood