Vesiculobullous Disorders (2) PDF

Vesiculobullous Disorders (2) Vesiculobullous Disorders Disorders affecting skin/mucous membranes o Blister: fluid filled cavity within or beneath the epidermis o Vesicles: 10mm Histologic Features for Diagnosis: Blisters can be secondary to: — Herpes — Spongiotic dermatitis — Burns — Lupus erythema...

Vesiculobullous Disorders (2) Vesiculobullous Disorders Disorders affecting skin/mucous membranes o Blister: fluid filled cavity within or beneath the epidermis o Vesicles: 10mm Histologic Features for Diagnosis: Blisters can be secondary to: — Herpes — Spongiotic dermatitis — Burns — Lupus erythematosus — Lichen planus — Scleroderma Level of plane of separation (ex. which layer gets separated) Presence/Absence of acantholysis (loss of intercellular desmosomes, change in cell shape) Keratinocytes: morphological features: Intercellular bridges Desmosomes o Strong intercellular (between cell) adhesion structure o Desmosomes are made of 5 proteins: § Desmoglein § Desmocollin § Desmoplakin § Plakoglobin § Plakophilin Hemidesmosomes o Strong adhesion structures btwn keratinocytes and the basement membrane o Aka btwn the epithelium and basal lamina Inflammatory Blistering Disorders Pemphigus Benign Autoimmune dz Assc with internal malignancies, including thymoma Intraepidermal vesicles assc w acantholysis Pathogenesis: IgG against desmoglein 1, 3 5 types of Pemphigus: o Vulgaris (most common dental) o Erythematosus o Foliaceus o Vegetans o Paraneoplastic Pemphigus Foliaceus - Auto antibodies form against Desmoglein 1 Pemphigus Vulgaris - Auto antibodies form against Desmoglein 3, and sometimes 1 Pemphigus Vulgaris Most common Involves mucosa, skin Blister filled w clear fluid * Blisters ruptures easily, becoming Ulcers seen in in ORAL CAVITY Suprabasilar bullae (>1cm) w single row of basal cells seen on basement membrane Pemphigus Erythematosus Localized area Resembles lupus malar rash Less severe variant of pemphigus foliaceus Which protein is impacted? - Desmoglein 1 Paraneoplastic Pemphigus Assc w internal tumor such as: o Lymphoma o Thymoma o Carcinoma of Bronchus, pancreas, breast Involves oral mucosa and skin Bullous Pemphigoid Subepidermal autoimmune dz IgG reacts against hemidesmosomal proteins o BP230 (BPAG 1) o BP180 (BPAG2) Seen in older pts Large, tense pruritis skin blisters on flexor surfaces Subepidermal nonacantholytic blisters Non-Inflammatory Blistering Disorders Epidermolysis Bullosa Cytokeratin network defects at dermal/epidermal junction Trauma induced Very early onset Diagnosis relies on age of onset, family hx Epidermolysis Bullosa Variants Simplex (most common) Junctional Dominant/Recessive Dominant Recessive Mutation/Defect Keratin 14, 5 Laminin 5 Blister/Vesicle Basal layer vesicle Blister in Lamina Lucida Location formation from degeneration of individual epidermal cells Pathology Intraepidermal tissue Skin can appear normal separation Stratum corneum, upper epidermis intact Dystrophic Dominant or Recessive Collagen VII (7) Blisters beneath Lamina Densa Subepidermal blister formation flat rete ridges Low anchor fibril count below lamina densa Can see mitten deformity Porphyria Disorder caused by disturbance of porphyrin metabolism Autosomal dominant unless congenital erythropoietic (autosomal recessive) Accumulation and increased excretion of porphyrins Manifests on skin as subepidermal vesicles Clinical Features: o Early metabolic intermediates -> neurologic dysfunction o Delta-aminolefulinic acid (DALA) -> Pain o Defected final steps-> photosensitivity Herpes Painful dz caused by: o Herpes Simplex virus (HSV) o Varicella Zoster virus (VZV) Dz process: o Grouped Vesicles on erythematous base o Vesicles become pustules then crust over Presence of multinucleated, acantholytic keratinocytes w distinct nuclear inclusions o Located in follicular epithelium Q: Which junctional proteins are involved in pemphigus vulgaris? - Desmoglein 3 or 1 Q: Which antibodies are against which type of protein