Vesiculo-Bullous Skin Flashcards
Types of Blisters
Subcorneal
* Stratum corneum forms roof
* Pemphigus foliaceus
Suprabasal
* Above basal layer forming floor
* Pemphigus vulgaris
Subepidermal
* Entire epidermis separates from the dermis
* Bullous pemphigoid
Pemphigus
- Pemphigus is a group of acantholytic conditions caused by autoantibodies against various epidermal cell junction proteins
- Flaccid blisters, erosions or scaling
4 main forms:
* pemphigus vulgaris (with pemphigus vegetans)
* pemphigus foliaceus
* paraneoplastic pemphigus
* newly described IgA pemphigus
Syndromes:
Most commonly associated with:
* B cell lymphoma
* Castleman
* Thymoma
* Waldonstroms macroglobulinaemia
Pathogenesis
* IgG or IgA autoantibody against epidermal antigens
Pemphigus vulgaris:
* IgG to desmoglein 1 (skin)
* desmoglein 3 (mucosa)
Pemphigus foliaceus:
* IgG to desmoglein 1
Paraneoplastic pemphigus:
* IgG to desmoplakin I
* desmoplakin II
* plectin
* periplakin
* envoplakin
* BP230 or A2ML1
IgA pemphigus:
* IgA to desmocollin 1 (subcorneal pustular dermatosis [SPD] variant);
* desmoglein 1
* desmoglein 3
Clinical features:
Pemphigus vulgaris:
* Mucosal erosions (oral or genital)
* painful flaccid blisters
* Hoarseness if larynx or pharynx are involved
Pemphigus vulgaris variants:
Pemphigus vegetans:
* Neumann type (severe)
* Hallopeau type (mild)
* Affects flexural areas
* blisters evolving into hypertrophic vegetations and pustules, cerebriform tongue
Pemphigus foliaceus:
* Affects seborrheic areas (face, scalp, upper trunk)
* Crusted superficial erosions
Paraneoplastic pemphigus:
* Mucosal involvement (severe stomatitis and conjunctivitis)
* Erythema multiforme-like (targetoid) lesions on the palms and soles
* Lichenoid lesions
* Bronchiolitis obliterans
IgA pemphigus:
* Small superficial blisters / pustules arranged in annular / arcuate plaques with crusting in the center; mucosae are usually not involved
Signs:
* Nikolsky sign: induction of blister / erosion by slight friction
* Asboe-Hansen sign: lateral extension of intact blister with gentle pressure
Micro:
Pemphigus vulgaris:
* Suprabasal acantholysis
* Basal layer remains attached (tombstone sign)
* Intraepidermal vesicles with round acantholytic keratinocytes
* Intraepidermal eosinophils and sometimes neutrophils
Pemphigus vegetans:
* Subtle suprabasal acantholysis
* Hyperplastic epithelium
* Intraepidermal eosinophils, microabscesses
Pemphigus foliaceus:
* Subcorneal acantholysis
* Rarely intact blisters
* Detached stratum corneum may show granular keratinocytes as cling ons
* Neutrophilic exocytosis
* Intraepidermal eosinophils
Paraneoplastic pemphigus:
* Variable
* Features of pemphigus vulgaris
* Lichenoid and vacuolar interface changes
IgA pemphigus:
* Subcorneal pustules (subcorneal pustular dermatosis variant)
* All layer epidermal pustules (intraepidermal neutrophilic variant)
Immunofluorescence description
Pemphigus vulgaris:
* intercellular IgG and C3 in the epidermis (chicken wire pattern)
Pemphigus foliaceus:
* Intercellular pattern, stronger fluorescence in the upper epidermis
Paraneoplastic pemphigus:
* linear or granular IgG at dermal epidermal junction; in 50% of cases, intercellular deposition is also seen
Pemphigus erythematosus:
* granular IgG at dermal epidermal junction
IgA pemphigus:
* intercellular IgA in the upper epidermis (SPD variant) or lower epidermis (IEN variant)
Bullous pemphigoid
- Most common autoimmune blistering skin disorder
- IgG Autoantibodies against hemidesmosomal antigens, bullous pemphigoid antigens 1 and 2 (BPAG1 and 2)
- tense bullae on an erythematous base and pruritus
- Elderly > children and infants
- Associated with medication use: Anti-PD1 immunotherapy, Diuretics, ACE inhibitors, antibiotics, D penicillamine
- Flexor surfaces
- Nikolsky sign is negative
Micro:
* Subepidermal blister
* Superficial perivascular mixed inflammatory infiltrate with eosinophils in the dermis and blister cavity
* Eosinophils may line up along the dermal epidermal junction and extend into the epidermis (eosinophilic spongiosis)
* Rare eosinophilic flame figures
Immunofluorescence:
* Linear IgG and C3 deposition along the basement membrane zone of epithelium, hair follicles and eccrine glands
* Only C3 may be present in early stage lesions
Salt split skin analysis:
* Direct immunofluoresence: localization of immunoreactants to either roof only (40%) or roof and blister (60%)
* Indirect immunofluorescence: localization of immunoreactants to the roof of the blister (95%)
Dermatitis herpetiformis
- Most cases are triggered by gluten ingestion and subsequent intolerance
- Anti tissue transglutaminase antibodies cross react with epidermal transglutaminase and leads to cutaneous deposits of IgA
- Subepidermal vesicles and blisters with papillary neutrophilic microabscesses that may contain eosinophils
- elbows, knees, buttocks and back, posterior shoulder, neck
- Enzyme linked immunoassay (ELISA) –> Circulating IgA antibodies to tissue transglutaminase
Micro:
* In early lesions, superficial perivascular lymphocytic and neutrophilic infiltrate
* Subepidermal vesicles or blisters with papillary neutrophilic microabscesses that may contain eosinophils
* Vacuolar interface changes and nuclear dust may be seen
* Dermal infiltrate contains lymphocytes, histiocytes and abundant neutrophils
* Acantholysis may also be present
Immunofluorescence description:
Direct immunofluorescence
* Granular IgA deposits in the dermal papillae
* Granular C3 deposits pattern in dermal papillae may be present
* Rare but characteristic fibrillar IgA deposits along the basement membrane zone
Epidermolysis bullosa acquisita
- Rare, noncongenital, autoimmune, chronic blistering disease of skin and mucus membranes
- Usually IgG autoantibodies against NC1 (noncollagenous domain of type VII collagen)
- Occurs at any age, usually affects elderly
- Blisters, scars and milia at trauma prone areas
Micro:
* Subepidermal blister with mixed inflammatory cell dermal infiltrate
* Often has bullous pemphigoid-like features
Immunofluorescence:
* Direct immunofluorescence on perilesional skin shows linear band of IgG along dermal-epidermal junction
Salt split skin analysis:
* IgG autoantibodies on dermal side of basement membrane
Porphyria cutanea tarda
- autosomal dominant disorder due to catalytic deficiency of uroporphyrinogen decarboxylase (UROD)
- Subepidermal blister
- Dermal papillae protrudes into bulla with festooned pattern; roof of blister has eosinophilic, PAS+ and diastase resistant linear globules –> Caterpilla bodies’
Darier disease
- Autosomal dominant
- mutations in ATP2A2 gene
- ATP2A2 encodes the sarco / endoplasmic reticulum Ca2+ ATPase isoform 2 (SERCA2)
- Family history
- Greasy hyperkeratotic papules
- Central chest, back, marginal scalp and face
- Nail changes: longitudinal erythro / leukonychia, subungual hyperkeratosis and V shaped nicking of the free edge of the nail
Micro:
* Parakeratosis
* Variable epidermal thickness
* Acantholysis with characteristic dyskeratosis forming corp ronds and grains
Corp rond:
* rounded keratinocyte in superficial spiny and granular layer with basophilic / pyknotic nucleus, perinuclear halo and often a rim of eosinophilic cytoplasm
Grain:
* elongated keratinocyte in the stratum corneum with small basophilic nuclei and intensely pink cytoplasm; appears as plump parakeratosis; may form tiers
* Suprabasal acantholysis and clefting with retained single layer of basal keratinocytes overlying dermal papillae which appear to project into the acantholytic cavity (villi)
Hailey-Hailey disease
- Autosomal dominant
- mutation in ATPC1 gene
- Vesicles may progress to bullae, then rupture, forming a crust
- Axillae, groin, perianal and inframammary areas
Micro:
* Suprabasilar and intraepidermal clefting
* Acantholysis of keratinocytes resembling dilapidated brick wall
* Epidermal hyperplasia
* Corps ronds and grains are rare
* Adnexal structures are spared
* Dermis shows variable chronic inflammatory infiltrate
* Parakeratotic crust may contain neutrophils and bacteria
* Immunofluorescence negative
Grovers Disease
- Transient papulovesicular eruption on the trunk
- Sporadic, reactive condition
- Multiple pruritic papulovesicular eruption
Micro:
* Suprabasal acantholysis with vesicle formation is the principal microscopic finding
* Elongation of rete ridges with focal acantholysis
* Eosinophils may be the only early changes in Grover disease
Main 4 histopathological patterns are:
* Pemphigus vulgaris / foliaceous-like: predominantly limited to suprabasal acantholysis, with basal keratinocytes attached to basement membrane forming a characteristic tombstone appearance
* Darier-like: suprabasal acantholysis of keratinocytes with scattered apoptotic or dyskeratotic cells within various levels of the epidermis
* Spongiotic: edema within epidermis, causing separation of keratinocytes and prominent intracellular bridges
* Hailey-Hailey-like: suprabasal acantholysis of all levels of the epidermis without significant dyskeratosis (dilapidated brick wall appearance)
More than one pattern can be seen in the same setting
