Vesiculo bullous diseases

VesiculoBullous Diseases

A vesiculobullous disease is a type of mucocutaneous disease that is characterized by vesicles and bullae (i.e. blisters).

Both vesicles and bullae are fluid-filled lesions, and they are distinguished by size (vesicles being less than 5-10 mm and bulla being larger than 5-10 mm)

Classification:-Viral diseases Herpes simplex infection Varicella-Zoster infection

Classification:-

Immunologic Disease Pemphigus Vulgaris Mucous membrane pemphigoid (MMP) Bullous Pemphigoid (BP) Dermatitis Herpetiformis Linear Immunoglobulin A disease (lAD)

Classification:-

Hereditary Disease Epidermolysis Bullosa Angina bullosa heamorrhagica

Herpes Simplex Infection Common vesicular eruption of skin and mucosa Forms:- HSV-1 1) Primary (Acute primary herpetic gingivostomatitis) 2) secondary or recurrent (Herpes Labialis / coldsores) HSV-2 (Genital Herpes)

Herpes Simplex InfectionPathogenesis:- Host(Seronegative) Direct Contact with HSV

Primary DiseaseGingivostomatitis

Secondary disease (lip, gingiva,palate) Host seropositiveLatent virus in Nerve Ganglia reactivation

Acute Primary Herpetic Gingivostomatitis Most common Viral Infection affecting mouth Usually seen in pre-school children , teenagers Clinical Features:- Prodromal features ( Headache, fever, malaise, lymphadenopathy, skin

rash) Oral and perioral vesicles appear & they rupture to form ulcers Oral ulcerations (typically all oral mucosa) Gingiva become boggy, ulcerated @ free margins, pain Course = 7-10days Lesions heal without scar formation

Viral DiseasesCase Presentation 1:- A child 10yrs old came to our clinic & presented with fever, sore throat,

headache, and vesicular eruptions in the oral cavity. On clinical examination his oral mucosa was bright red , sore , and he had marked gingivitis and his cervical lymph nodes were palpable

Viral DiseasesCase presentation 2:-A 2 yr old girl reports to you with a complaint of widespread oral ulcerations & gingival swelling with a history of fever & sore throat for 2 days

What is your DIAGNOSIS????How ill You MANAGE the patient????

Diagnosis:- History Clinical Examination Additional Investigations:- 1)Viral swab-culture EM, PCR 2)Vesicular fluid-tzank cells 3)Viral Antibody titers (IgM,IgG)

DIAGNOSIS“Primary Herpetic Gingivostomatitis”MANAGEMENTIn childhooda) Antipyretics paracetamolb) Analgesics paracetamolc) Local analgesics benzydamine HCL m/w or spray, lidocaine

gel 1-2%d) Fluidse) Antihistaminesf) Monitor temperature

MANAGEMENT In adultsa) Antipyretics (paracetamol or NSAIDS)b) Analgesicsc) Fluidsd) Acyclovir-200mg 5x daily for 5 days

Secondary Herpes Infection Reactivation of the latent herpes virus type 1 Precipitating factors :- Sunlight exposure Exposure to cold Trauma Stress Immunosuppression Pregnancy Other illness

Clinical Features Prodromal symptoms (Tingling & Burning) Mucocutaneous junction of the Lip Pururitis ,reddening , Vesiculation ,

Pustule , Ulcer Intraoral recurrences (Hard palate, gingiva) Self limited

Diagnosis:- History Clinical examination Occasionally identify by culture PCR Serology not helpfulManagement:- Acyclovir cream 5% 4 hourly Penciclovir cream 1% 2 hourly

Varicella Zoster Infection Childhood - Primary infection> Chicken Pox Adulthood – Secondary infection > ShinglesChicken Pox:-Common diseaseRoute of spread (direct contact, droplet infection)Clinical Features:-Prodromal features Oral vesicles or Ulcers typically on palateSkin Rash primarily involve trunk head and neckPruritic>papular>vesicular>pustular>crusts>trunk/face esp. affected/first sites

Investigations History Clinical Examination Virus identified by culture EM, PCR

Treatment Analgesics Antipyretics

Herpes Zoster(Shingles)Middle or Older AgePredisposing Factors (debilitating diseases immunosuppression , cancer )Clinical Features Vesicular Eruption in area of Distribution of sensory nerve Band like distribution of shingles on trunk(zoster, girdle) Trigeminal Nerve most commonly ophthalmic division involve-corneal

ulcerationC/f in the mouth:- Unilateral Vesicles breakdown to form ulcers

Ramsay hunt Syndrome:- Involvement of Facial in auditory nerve produce ramsay hunt syndroe Lower motor neuron facial palsy Otitis Externa Vesicles of ant 2/3rd tongue Vesicles or ulcers of soft palate

Investigations:- History Clinical Examination FBC Rarely-identify virus (e.g. culture, EM, PCR) Serology not helpfulTreatment:- Analgesics Antiviral agents Aciclovir , valaciclovir, famciclovir ,brivudin Aciclovir (800mg 5times/day for 7-10days) Tetracycline mouth washes (for oral lesions)

Viral Diseases

Case presentation A 65yr old male presented to clinic with tooth Ache for

2-3days after that vesicles appear on palate , accompanied by corneal ulceration. Similar vesicles are aslo present on skin and form firm crust.

Hereditary Diseases:-Epidermolysis BullosaA generalized desquamating condition of the skin & mucosa with associated scarring , contractures , & dental defects that occur in 3 main hereditary forms in children & one acquired form in adultsTypes:-Type Genetic Pattern Location of

separationDefective StructureHereditary

Simplex Autosomal dominant Intraepithelial Linking proteinsJunctional Autosomal recessive Lamina Lucida Anchoring proteinsDystrophic Autosomal

dominant/recessiveSublamina Densa Type 7 collagen

AcquiredAcquista None Sublamina Densa Type 7 collagen

Clinical Features:-Simplex Epidermolysis Bullosa Skin blisters at birth, mainly induced by friction. Oral involvement absent or mild. Teeth normal Site of Blister:- Basal cells Inheritance:- Mainlu autosomal dominant

Clinical Features:- Junctional epidermolysis bullosa Lethal form results in extensive skin & mucosal involvement , dental abnormalities & often with death in infancy. The nonlethal form produces widespread skin & variable mucosal

involvement Intraorally large fragile heamorragic blisters of palate Crusted granular heamorrahagic lesions present in perioral and perinasal

Clinical Features:-Dystrophic Epidermolysis Bullosa Dominant form is often mild. Recessive form is very severe with extensive blisters & scarring of skin, Loss of nails Severe oral mucosal blistering & scarring results in diminished opening Hypoplastic teeth Epidermolysis bullosa acquisita Trauma or friction induced blisters Intraoral blisters rare If present, they produce scarring & diminished oral opening

Management:- No specific TX available! Avoidance of trauma Prevention of infections Systemic use of phenytoin Corticosteroids (high doses ) Systemic use of phenytoin (Dilantin) Vitamin E Retinoids Dapsone Maintaninance of nutritional status is required in case of restricted oral

opening

Idiopathic oral blood blisters(Angina bullosa hemorrhagica) Formation of spontaneous blood filled bullae (blood blisters) of oral

mucosa Both GENDERS affectedClinical Features Sharp pricking sensation Most commonly on palate Bullae may be quite large 2-3cm Commonly occur when pt is eating

Mechanism:- Bleeding from the capillary bed below a basal zone that is for some

reason weakend Pt with thrombocytopenia may develop blood blistersDiagnosis:-HistoryFull blood count Clotting screenManagement:-Perforation of large intact blister is necessaryAntiseptic mouth washes (Chlorhexidine gluconate)Analgesic mouth washes (Benzydamine HCL)No preventive TX

What is an Immunologic Disease ?

A disease resulting from a disordered immune reaction in which antibodies are

produced against one's own tissues, as systemic lupus erythematosus or rheumatoid arthritis.

Immunologic Disease Pemphigus Vulgaris Immunobullous disorder Middle-age disease (40-60yr) Affects :- Skin & Mucous membrane 50% cases begin in mouth (First to SHOW last to GO) Characterized by :- 1)Intraepithelial Blister formation 2)Painful ulcers preceded by bulla 3)Bullae are fragile & breakdown rapidly to form CRUSTED, ERODED lesions 4)Ulcers range from small APTHOUS like to large MAP like lesions

Nikolsky’s Sign Gentle traction on clinically unaffected mucosa may produce stripping

of epithelium, a +ve nikolsky sign

Pathogenesis:- Circulating autoantibodies IgG

Reactive against epithelial desmosome-tonofilament complexes (Desmoglein 3)

result in dissolution or disruption of intercellular junctions & loss of cell to cell adhesion

Types:- Pemphigus Vulgaris Pemphigus Foliacues Pemphigus Erythematous Pemphigus Vegetans IgA type Drug Induced

Vulgaris/vegetans Affect the Whole Epithelium Erythematous/Foliaceus Upper Prickle cell layer

Intraoral Blisters

Diagnosis:- History Clinical examination Red painful ulcers Bullae formation +ve nikolsky’s sign small vesicles on soft palate, buccal mucosa, floor of the mouth Immunofluorescence (DIF) Fish-net appearance (IgG, C3 )(IDIF) +ve IgG 90%

ELISA

o

These changes are seen in the STRATUM SPINOSUM or THE PRICKLE CELL LAYER

The basal cells loose their intercellular bridges but they remain attach to the dermis, giving a TOMBSTONE appearance

The blister cavity contains acantholytic cells which often show degenerative changes

Tzank cells

Intraoral image:-

D/D MMP EM Erosive lichen planus Paraneoplastic pemphigus Apthous Ulcers

Management Systemic CorticosteroidsA) AzathioprineB) MethotrexateC) CyclophosphamideD) Cyclosporine

A) Other:-B) Mycophenolate mofetilC) Plasmapheresis In sick people,

plasma can contain antibodies that attack the immune system.

D) Levamisole (Discontinued)

E) ImmunoglobulinsF) High dose iv IgG) Infliximab

TX MonitoringWeight Blood pressure

TX MonitoringBlood glucose LFT’sFull blood count

TX MonitoringRenal function test Cataracts

Mucous membrane pemphigoid Chronic blistering disease Affects:- oral & ocular mucous membrane Adults and elderly (affect women more than men) Characterized by:- Sub-epithelial bulla formation intraoral intact bullae present on gingiva or soft palate ulcerated area of mucosa involve buccal, palatal or lip mucosa desquamative gingivitis lesions are chronic & persistent heal with a scar (cicatrix) particularly

lesions of eye

Usually Buccal mucosa Gingiva & soft palate

Types:- Cicatrical Pemphigoid Benign mucous membrane pemphigoid Ocular Pemphigus Childhood Pemphigoid Mucosal Pemphigoid Gingivosis

Risks include:- Symblephron, entropion, trichiasis

Pathogenesis:- Auto-Antibodies IgG

Target antigen BP 180 & laminin 5

Result in sub-epithelial clefting

D/D

Pemphigus vulgaris Erosive lichen planus If attatched gingiva involve then ; atrophic lichen planus , linear igA disease , contact allergy , DLE

Diagnosis History (Drug history, drug induced) Biopsy (Sub epithelial blister formation) Direct Immunofluorescence (linear IgG @ BM) Indirect Immunofluorescence (Pemphigoid antibodies)

Management Topical corticosteroids Systemic corticosteroids Azathriopine Dapsone (diaminodiphenylsulfone) 25 mg & 100 mg Tablets for

Oral Use High dose IV ig Referral for Eyes, skin, larynx, genitalia

Bullous Pemphigoid Sub epidermal blisters Elder 7th & 8th decade Involves Skin & mucous membrane Characterized by:- Skin lesions (Tense vesicles on trunk and limbs) preceded by

erythematous popular eruption Oral lesions (bullae & erosions mostly noted on attached gingiva) Other sites:- soft palate , buccal mucosa & floor of mouth

Diagnosis History Biopsy demonstrate IgG or c3 in a linear distribution Main target antigen BP 230 & BP 180 BP 230 & BP 180 Important proteins in maintaining the

structural integrity of the basement membrane i.e. in providing COHESION of the dermis to the epithelium

Management Systemic corticosteroidsPrednisolone 0.75-1mg/kg daily As soon as, control is reached tapering to maintenance dose of 8mg daily Topical CorticosteroidsAzathioprineCyclophosphamideMycophenolate also appear promising

Dermatitis Herpetiformis Cutaneous disease Young and middle age adults More common in males Associated with Gluten sensitive enteropathy –celiac disease Characterized by:- Cutaneous lesions:- Papular, erythematous, vesicular, intensely

pruritic (extensor surfaces of elbow, shoulder, sacrum, buttocks) Frequent involvement of scalp and face Oral cavity (uncommon vesicles and bullae that rupture leaving

superficial ulcers)

Pathogenesis:- Auto-Antibodies IgA

Binds with Epidermal transglutaminase

DiagnosisHistoryBiopsy (fluid filled sub epithelial bullaeDirect immunofluorescence – Granular deposits of IgA at BMSerology for Celiac disease- As the disease gets worse, more antibodies will be present. If a disease is suspected, the test may need to be repeated 10 days to 2 weeks after the first test.Full blood countLET’S may be abnormal

Management Dapsone 50 mg orally once a day continued on a life-long basis.

Dosage may be advanced to 300 mg/day. Dosage reduction to a minimum maintenance level as soon as possible is recommended.

Sulfoxone rapidly absorbed Sulfapyridine Gluten free diet

Linear IgA disease Rare bullous disease of skin 2 Types:- 1)Affecting children (chronic bullous disease of childhood) 2)Adults (Adult linear IgA disease) Characterized By:- Skin lesions Tense bullae on trunk, limbs or scalp (ROSETTES) Oral lesions Ulcerative or erosive similar to those seen in pemphigoid

Drug Induced Linear igA Vancomycin Diclofenac Captopril Cotrimoxazole Amiodarone Cyclosporine Glibencamide Lithium Penicillin Cefamandole Phenytoin Somatostatin Sodium hypochlorite (bleach)

Management Gluten free diet Topical corticosteroids Dapsone Sulfapyridine Referral regarding celiac disease