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: <1cm o Bullae: >1cm Histologic Features for Diagnosis: • Level of plane of separation • Presence/Absence of acantholysis • Im...

Vesiculobullous Disorders (2) Vesiculobullous Disorders • Disorders affecting skin/mucous membranes o Blister: fluid filled cavity within or beneath the epidermis o Vesicles: <1cm o Bullae: >1cm Histologic Features for Diagnosis: • Level of plane of separation • Presence/Absence of acantholysis • Immunofluorescence pattern Blisters can be secondary to: — Herpes — Spongiotic dermatitis — Burns — Lupus erythematosus — Lichen planus — Scleroderma Keratinocytes: morphological features: Intercellular bridges • Desmosomes o Strong intercellular (between cell) adhesion structure o Has an Outer dense plaque (ODP), and Inner dense plaque (IDP) 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 • 5 types of Pemphigus: o Vulgaris (most common dental) o Erythematosus o Foliaceus o Vegetans o Paraneoplastic • Pathogenesis: IgG against desmoglein 1, 3 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 esp in oral cavity • Healing assc w post-inflammatory hyperpigmentation • Death can occur from Staph infection, pulmonary embolism • Suprabasilar bullae (>1cm) w single row of basal cells seen on basement membrane Pemphigus Erythematosus • Seen in middle aged adults • 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 o Does not rupture easily o Heal w/o scarring unless infected • 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