Oral Vesicular Bullous disorders O R A L B L I S T E R I N G D I S O R D E R S
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1 Oral Vesicular Bullous disorders O R A L B L I S T E R I N G D I S O R D E R S
2 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
3 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
4 Mechanisms of blistering Inherited mutational defects of basement membrane proteins Autoantibodies Cellular immune mediated disorders Metabolic disturbance Subepidermal edema Acute inflammatory process
5 Classification - Oral blistering lesions According to clinical course: o Acute lesions: Primary herpetic gingivostomatitis Herpes zoster Erythema multiforme
6 o Chronic lesions: Pemphigus Bullous pemhigoid Bullous lichen planus
7 According to etiology: o Hereditary/Inherited disorders: Epidermolysis bullosa Dyskeratosis congenita Familial benign chronic pemphigus
8 o Autoimmune/Immunological/immune mediated disorders: Erythema multiforme Pemphigus Bullous pemphigoid Bullous lichen planus Cicatricial pemphigoid Linear IgA disease Dermatitis herpeteformis
9 o Infectious disorders: Bacterial infections: Congenital syphilis Fungal infections: Id reaction
10 Viral infections: Primary herpetic gingivostomatitis Herpes zoster/ Chicken pox Herpangina Hand, Foot and Mouth disease
11 o Miscellaneous: Allergic stomatitis Oral submucous fibrosis Burns and scalds
12 According to histology: o Intraepithelial/ Suprabasal lesions: Pemphigus Familial benign chronic pemphigus Primary herpetic gingivostomatitis Herpes zoster Herpangina
13 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
14 o Both intraepithelial & subepithelial: Erythema multiforme Epidermolysis bullosa Paraneoplastic pemphigus
15 Classification Oral ulcerative lesions According to clinical course: o Acute lesions: ANUG Aphthous ulcers Herpetic gingivostomatitis
16 o Chronic lesions: Malignant ulcer Traumatic ulcer Tuberculous ulcer o Recurrent lesions: Aphthous ulcers RHL/RIH Cyclic neutropenia Behcet s syndrome
17 According to onset: o Primary lesions: Traumatic ulcers Malignant ulcers Tuberculous ulcers o Secondary lesions: Herpes zoster AHGS/ RHL/RIH Pemphigus
18 According to number: o Solitary ulcers: Traumatic ulcers Malignant ulcers Tuberculous ulcers Deep fungal ulcers
19 o Multiple ulcers: AHGS/ RHL/RIH Aphthous ulcers Pemphigus Erythema multiforme
20 According to etiology: o Traumatic ulcers: Physical TUGSE Traumatic ulcer Chemical Chemical burn Aspirin burn Thermal Pizza burn Electric burns
21 o Infectious ulcers: Bacterial Tuberculous ulcer Syphilitic ulcer Leprosy ANUG
22 Viral ulcers AHGS/ RHL Herpes zoster Herpangina Hand, foot & mouth disease
23 Fungal ulcers Candidiasis Mucormycosis Histoplasmosis Cryptococcosis Blastomycosis
24 o Autoimmune/ Immune mediated: Pemhigus Pemphigoid Erythema multiforme Lichen planus Discoid lupus erythematosus
25 o Nutritional deficiencies: Vitamin B complex Iron o Hematologic disorders: Leukemia Agranulocytosis Neutropenia/ cyclic
26 o Neoplastic ulcers: Squamous cell carcinoma Adenoid cystic/ adenocarcinoma Mucoepidermoid carcinoma Melanoma lymphoma
27 o Preneoplastic ulcers: Lichen planus Oral submucous fibrosis Discoid lupus erythematosus o Miscellaneous Allergic stomatitis
28 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
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36 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
37 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
38 Recurrent herpes labialis Cold sore, Fever blister Predisposing factors: trauma, fever, stress, menstruation, immunosuppression,sunburn, cold Tingling and burning, vesicles, clusters
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41 Recurrent intraoral herpes Vesicles, clusters keratinised mucosa Ulcers
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44 Diagnosis Cytology Viral isolation
45 Treatment Acyclovir, Valacyclovir Famciclovir, Penciclovir Docosanol
46 Herpangina Coxsackie A4 Incubation period: fever, malaise Sore throat, dysphagia Vesicles, rupture into ulcers
47 Occurs in epidemics Milder Pharynx, posterior oral cavity Gingivitis absent Smaller lesions
48 Diagnosis / treatment Cytology Self limiting Rest, fluid, electrolyte balance Topical anesthetics
49 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
50 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
51 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
52 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
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63 Diagnosis Cytology- Tzanck smear Serology: rising antibody titer Viral isolation
64 Treatment Acyclovir- 800mg 5 /day, Valacyclovir, Famciclovir Corticosteroids? Intralesional steroids+ local anesthetics Topical capsaicin Tricyclic antidepressants, Gabapentin Chemical/surgical neurolysis
65 DISEASE CLINICAL FEATURES CAUSE SIGNIFICANCE Primary herpetic gingivost omatitis Multiple painful oral ulcers preceded by vesicles; may have similar perioral and skin lesions, fever and gingivitis is usually present; usually affects children below 5 years of age Herpes simplex virus type 1 (occasionally type 2) Self limited, heals in about 2 weeks, reactivation of latent virus results in secondary infections; circulating antibodies provide only partial immunity
66 DISEASE CLINICAL FEATURES CAUSE SIGNIFICANCE Secondary herpes simplex infection Multiple small ulcers preceded by vesicle; prodromal symptoms of tingling; burning or pain; most common on lip; intraorally on palate and attached gingiva; adults and young adults usually affected; very common; called herpetic whitlow when occurs on fingers Herpes simplex virus - represents reactivation of latent virus and not reinfection; commonly precipitated by stress, sunlight, cold temperature, low resistance and immunodeficien cy Self limited, heals in about 2 weeks, without scar; lesions infectious during vesicular stage, patient must be cautioned against autoinoculation; herpes type 1 infections have not been linked convincingly to oral cancer; any site affected in AIDS patients
67 DISEASE CLINICAL FEATURES CAUSE SIGNIFICANCE Varicella Painful pruritic vesicles and ulcers in all stages on trunk and face; few oral lesions; common childhood disease Varicella virus zoster Self limited, recovery uneventful in several weeks Herpes Zoster Unilateral multiple ulcers preceded by vesicles distributed along a sensory nerve course; very painful; usually on trunk, head and neck; rare intraorally; adults Varicella zoster virus- Reactivation of latent virus Self-limited, but may have a prolonged, painful course; seen in debilitation, trauma, neoplasia and immunodeficiency
68 DISEASE CLINICAL FEATURES CAUSE SIGNIFICANCE Hand foot mouth disease Painful ulcers preceded by vesicle on hands, feet and oral mucosa; usually children; rare Coxsackie viruses Self limited, recovery uneventful in about 2 weeks Herpangina Multiple painful ulcers in posterior oral cavity and pharynx; lesions preceded by vesicles; children most commonly affected; seasonal occurrence; rare Coxsackie viruses Self limited, recovery uneventful in less than a week
69 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
70 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
71 Variants: Steven Johnson syndrome Toxic epidermal necrolysis
72 Etiology: Hypersensitivity reaction An immune mediated disease- deposition of immune complexes in the superficial microvasculature of skin & mucosa Idiopathic- no obvious detectable cause
73 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
74 Benign, malignant tumors Radiotherapy Crohn s disease, sarcoidosis Stress, emotional factors
75 Clinical features: Clinical features: Children & young adults years, men Acute, explosive onset Prodromal symptoms- fever, malaise, headache, sore throat, rhinorrhoea, cough
76 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
77 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
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82 Stevens Johnson syndrome (SJS)/ Toxic epidermal necrolysis (TEN): Medications, mycoplasma pneumoniae Severe lesions- erosions, bullae, ulcers, crusted lips Chest> extremities- atypical targets
83 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
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85 Differential diagnosis: Primary herpetic gingivostomatitis Pemphigus Paraneoplastic pemphigus Pemphigoid Aphthous stomatitis
86 Diagnosis: History Clinical findings Biopsy
87 Management: Self limiting Mild- supportive ie topical anesthetics, soft, liquid diet, rehydration Moderate/severe- systemic corticosteroids mg/d prednisone, methylprednisolone
88 Prophylactic Acyclovir- 400mg BID, Valacyclovir- 500mg BID Azathioprine, Dapsone mg/d SJS/TEN- burn centers- removal of necrotic skin with grafting
89 Pemphigus Autoimmune, chronic, life threatening mucocutaneous diesease Types: Pemphigus vulgaris Pemphigus vegetans Pemphigus erythematosus Pemphigus foliaceous Paraneoplastic pemphigus Drug related pemphigus
90 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
91 Clinical features: Adults years, no sex predilection Pemphigus vulgaris most common- 80% Thin walled bullae- break rapidly Extend peripherally- large denuded areas of skin, mucosa
92 Nikolsky s sign- positive Asboe Hansen sign- positive Upper layer of the skin, mucosa pulling away from the basal layer
93 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
94 Differential diagnosis: Primary herpetic gingivostomatitis Erythema multiforme Pemphigoid Lichen planus Aphthous stomatitis
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103 Diagnosis: History Clinical findings Cytology-Tzanck smear- acantholytic cells Biopsy- intraepithelial split Immunofluorescence Direct- positive, intercellular Indirect- positive, circulating autoantibodies
104 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
105 Paraneoplastic pemphigus Severe variant, associated with an underlying neoplasm- Non -Hodgkin s lymphoma Chronic lymphocytic leukemia Thymoma Castleman disease Waldenstrom macroglobulinemia
106 Clinical features Adults 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
107 Diagnosis/ Management History Clinical features Biopsy Treat underlying disease Corticosteroids+ azathioprine, methotrexate, cyclophosphamide Fatal
108 Drug induced pemphigus Penicillamine, penicillin, phenobarbital, ACE inhibitors- captopril, NSAID s Discontinuation of drug- spontaneous recovery
109 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
110 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
111 Can occur in association with Multiple sclerosis Malignancy Drug therapy- diuretics
112 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
113 Oral findings % Vesicles, bullae- small, form slowly, less painful Desquamative gingivitis
114 Differential diagnosis Pemphigus Mucous membrane pemphigoid Lichen planus- bullous, erosive
115 Diagnosis History Clinical features Biopsy Immunofluorescence Direct- positive, basement membrane Indirect- not reliable
116 Management Corticosteroids systemic, topical Steroid sparing agents- azathioprine, cyclophosphamide, mycophenolate Dapsone, tetracycline, doxycycline, minocycline + niacinamide
117 Mucous membrane pemphigoid Cicatricial pemphigoid A chronic, autoimmune disorder Autoantibodies directed against basement membranesubepithelial vesicle formation Primarily affects mucous membrane Association with underlying malignancy?
118 Clinical features Adults, > 50 years Women> men Any mucosa, oral mucosa, conjunctiva, laryngeal, genital, oesophagal, skin
119 Oral findings 90% Desquamative gingivitis Vesicles, bullae- intact Erosions, ulcerations Spread slowly, self limiting
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121 Diagnosis History Clinical features Biopsy Immunofluorescence Direct- positive, basement membrane
122 Management Corticosteroids- topical, intralesional, systemic Soft splint covering gingiva to hold medicament Tetracycline, doxycycline, minocycline Dapsone, immunosuppressants
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124 Linear IgA disease Etiology Unknown Drug induced Associated with hematologic malignancies, dermatmyositis
125 Clinical features Pruritic papules and blisters- skin, elbows, knees Oral mucosa, conjunctiva
126 Oral findings 70% Similar to MMP Vesicles, bullae, erosins, ulcerations of oral mucosa Desquamative gingivitis
127 Diagnosis History Clinical features Biopsy Immunofluorescence Direct- positive, basement membrane (IgA) Indirect- usually negative
128 Management Corticosteroids- topical, systemic Dapsone, sulfapyridine, tetracycline+ niacinamide Immunosuppressants
129 Epidermolysis bullosa aquisita
130 Chronic bullous disease of childhood
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