intraepidermal immunobullous diseases

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INTRAEPIDERMAL IMMUNOBULLOUS DISEASES : 

INTRAEPIDERMAL IMMUNOBULLOUS DISEASES By: Dr. Deepak Kumar

IMMUNOBULLOUS DISEASES : 

IMMUNOBULLOUS DISEASES INTRAEPIDERMAL PEMPHIGUS Group SUBEPIDERMAL BULLOUS PEMPHIGOID MUCOUS MEMBRANE PEMPHIGOID PEMPHGOID GESTATIONIS LINEAR IgA DISEASE BULLOUS SLE DERMATITIS HERPETIFORMIS EPIDERMOLYSIS BULLOSA ACQUISITA

INTRAEPIDERMAL IMMUNOBULLOUS DISEASES : 

INTRAEPIDERMAL IMMUNOBULLOUS DISEASES Autoantibodies against cell-cell adhesion molecule Immune complexes deposited b/w keratinocytes Cells separate from each other Blisters within the Epidermis

Types of pemphigus : 

Types of pemphigus Pemphigus Vulgaris Pemphigus Vegetans Pemphigus Foliaceus P. Herpetiformis P. Erythemetosus Induced Pemphigus Intercellular IgA Dermatosis Paraneoplastic Pemphigus

Intercellular adhesion : 

Intercellular adhesion Adherens Junction Desmosomes Cadherins Desmogleins Desmocollins Submembranous Plaque Plakophilin Plakoglobin Desmoplakin

Desmosomes : 

Desmosomes

Pemphigus Vulgaris : 

Pemphigus Vulgaris 70% of all pemphigus patients. Both sexes Middle age More common in Jews and people of Mediterranean descent. HLA-DRB1

pathogenesis : 

pathogenesis Pemphigus vulgaris antigen Desmoglein 3(Dsg3) Antibodies IgG4

Clinical features : 

Clinical features Oral lesions 50–70% of patients

Clinical features : 

Clinical features Cutaneous lesions Flaccid blisters Erosions heal without scaring

diagnosis : 

diagnosis

histopathology : 

histopathology Acantholysis Clefts and blisters Row of tombstones

TZANCK PREPARATION : 

TZANCK PREPARATION ACANTHOLYTIC ,FREE FLOATING CELLS

ELECTRON MICROSCOPY : 

ELECTRON MICROSCOPY Widening of intercellular space Cytokeratin tonofilaments retract around the nucleus Desmosomal plaques disappear Attachment of basal cells to BM is not affected

immunofluorescence : 

immunofluorescence

Pemphigus vegetans : 

Pemphigus vegetans Rare variant of pemphigus vulgaris Disease starts -- earlier age Oral mucosa involvement -- almost invariable Lesions -- primarily flexural Two subtypes Neumann pemphigus vegetans Hallopeau pemphigus vegetans

PEMPHIGUS VEGETANS : 

PEMPHIGUS VEGETANS NEUMANN TYPE Vesicles and bullae rupture to form hypertrophic granulating erosions Vegetating masses exuding serum and pus HALLOPEAU TYPE Pustules characterize early lesions progress to vegetating plaques

Clinical features : 

Clinical features

HISTOPATHOLOGY : 

HISTOPATHOLOGY The vegetating lesions are hyperkeratotic, papillomatous and acanthotic Eosinophilic microabscesses – common in Hallopeau type Dermis infiltrated lymphos, eosinophils & some neutros Direct IMF: show IgG

Differential diagnosis of pemphigus vulgaris : 

Differential diagnosis of pemphigus vulgaris Oral lesions Acute herpetic stomatitis Erythema multiforme Aphthous ulcers Bullous lichen planus

Acute Herpetic Stomatitis : 

Acute Herpetic Stomatitis

Erythema Multiforme : 

Erythema Multiforme

Aphthous Ulcers : 

Aphthous Ulcers

ORAL LICHEN PLANUS : 

ORAL LICHEN PLANUS

Differential diagnosis of pemphigus vulgaris : 

Differential diagnosis of pemphigus vulgaris Cutaneous lesions Bullous pemphigoid Dermatitis herpetiformis Hailey – Hailey disease Darier’s disease Grover’s disease

Bullous pemphigoid : 

Bullous pemphigoid

Dermatitis herpetiformis : 

Dermatitis herpetiformis

Darier's disease : 

Darier's disease

Grover's disease : 

Grover's disease

Hailey - Hailey disease : 

Hailey - Hailey disease

treatment : 

treatment Topical therapy Systemic therapy

Topical therapy : 

Topical therapy Potent topical or intralesional steroids Good oral hygiene Potassium permanganate and topical antiseptics Oral Antifungal

Systemic therapy : 

Systemic therapy Prednisolone 1.0–1.5 mg/kg/day in combination with topical. High dose Prednisolone 120–240 mg/day for severe pemphigus Azathioprine 2.5 mg/kg/day Combination more effective Oral and Intramuscular Gold Tetracycline in combination Dapsone

Systemic therapy : 

Systemic therapy Cyclophosphamide 1–3 mg/kg/day in combination Ciclosporin 5mg/kg/day Mycophenolate mofetil 2 g/day as steroid sparing Plasmapheresis reduces the titres of autoantibody by 15% Methotrexate not effective High-dose intravenous immunoglobulin Extracorporeal Photophoresis with PUVA

Pemphigus Foliaceus : 

Pemphigus Foliaceus Blistering is high in the epidermis, granular layer or just beneath the stratum corneum. 10–20% of cases of pemphigus Pemphigus Foliaceus antigen is desmoglein 1 Antibodies IgG

Clinical features : 

Clinical features Scattered scaly lesions involving the ‘seborrhoeic’ areas: scalp, face, chest and upper back Crusted erosions surrounded by erythema Oral lesions are uncommon

Clinical features : 

Clinical features

histopathology : 

histopathology Vacuoles form in the intercellular spaces in the upper levels of the epidermis

pemphigus herpetiformis : 

pemphigus herpetiformis Cluster of pruritic papules and vesicles on erythematous background Biopsies show subcorneal pustules without acantholysis Immunofluorescence--- intercellular staining

Pemphigus erythematosus (Senear -Usher syndrome) : 

Pemphigus erythematosus (Senear -Usher syndrome) Immunological features of both lupus erythematosus and pemphigus ANA present Erythematous scaly lesions over the nose and cheeks in a butterfly distribution Lesions on the trunk similar to P. Foliaceus

pemphigus erythematosus : 

pemphigus erythematosus

Differential diagnosis of pemphigus Foliaceus : 

Differential diagnosis of pemphigus Foliaceus Seborrhoeic dermatitis Impetigo

Seborrhoeic dermatitis : 

Seborrhoeic dermatitis

impetigo : 

impetigo

treatment : 

treatment Potent topical or intralesional steroids Prednisolone 20–40 mg/day Hydroxychloroquine 200 mg twice daily Azathioprine or cyclophosphamide are adjuncts Dapsone 100–300 mg/day Drug of choice for P. Herpetiformis I.V IG -- resistant cases Mycophenolate mofetil

prognosis : 

prognosis P. Foliaceus is a benign but chronic ds Responds well but remit

ENDEMIC P. FOLIACEUS (WILD FIRE, FOGO SELVAGEM) : 

ENDEMIC P. FOLIACEUS (WILD FIRE, FOGO SELVAGEM) Endemic to South America Environmental factor – Insect bite Black Fly – risk factor Affects children & young adults Flaccid bullae which rupture easily leaving erosions Nikolsky's sign is +ve

ENDEMIC P. FOLIACEUS : 

ENDEMIC P. FOLIACEUS Head & neck involved 1st Sun exposure causes burning sensation Oral mucosa usually spared Chronic ds is frequent with disseminated verrucous lesions Growth retardation is common

TREATMENT : 

TREATMENT Similar to other P. foliaceus Topical steroids for localized ds Most pts respond to systemic steroids Immunosuppressive agents, gold & antimalarials are recommended

PROGNOSIS : 

PROGNOSIS Before steroids 40-60% pts died Now mortality reduced to 10% Spontaneous remission have been reported

INDUCED PEMPHIGUS : 

INDUCED PEMPHIGUS Drugs – induce / exacerbate P. foliaceus or P. erythematosus are common Prognosis : spontaneous remission on drug withdrawal 40-50 % of Thiol gp drugs 15 % of Non thiol drugs

DRUGS : 

DRUGS

INTERCELLULAR IgA DERMATOSIS : 

INTERCELLULAR IgA DERMATOSIS Intercellular IgA deposition in epidermis Affects adults Flaccid vesicles / pustules Sites Axillae, groin, face, trunk, scalp Treatment Responds to Dapsone Poorly to steroids

SUBCORNEAL PUSTULAR DERMATOSIS : 

SUBCORNEAL PUSTULAR DERMATOSIS Chronic, relapsing pustular eruptions Involves mainly trunk, flexures More common in females, 40-50 yrs Subcorneal neutrophils Negative IMF Dapsone is the treatment of choice

PARANEOPLASTIC PAMPHIGUS : 

PARANEOPLASTIC PAMPHIGUS Pemphigus associated with underlying neoplasm B-cell Lymphoproliferative disorders Thymoma, Sarcomas & Carcinomas Pts have severe mucosal erosions & polymorphous skin lesions – blisters, erosions 2/3rd cases – existing neoplasm 1/3rd cases – neoplasm detected after lesions

PARANEOPLASTIC PAMPHEGUS : 

PARANEOPLASTIC PAMPHEGUS BIOPSY: necrosis of keratinocytes with suprabasal clefting & acantholysis DIMF– reveals Ig or complement at BM zone & also at keratinocytes Antiplakin antibodies of IgG1 subclass But not specific

TREATMENT : 

TREATMENT Refractory to all treatment Steroids, AZT, Ciclosporin, Mycophenolate mofetil, plasmapheresis have been tried DEATH Sepsis GI bleeding Multiorgan failure Respiratory failure