Thursday, November 19, 2015

Cutaneous Blistering Disorders

Blistering skin disorders are among the most interesting, but also the most challenging conditions in dermatology and dermatopathology.

Blisters are accumulations of fluid within or under the dermis. There are three types of blistering skin diseases—subcorneal, intraepidermal, and subepidermal. Subcorneal blisters have a very thin roof that breaks easily. Examples include impetigo, miliaria, and Staphylococcal scaled skin syndrome (SSSS). Intraepidermal blisters have a thin roof that ruptures and leaves a denuded surface, as seen in acute eczema, varicella, herpes simplex, and pemphigus. Subepidermal blisters have a tense roof that often remains intact. Examples of subepidermal blisters are bullous pemphigoid, dermatitis herpetiformis, erythema multiforme, toxic epidermal necrolysis (TEN), and friction blisters.

The mechanisms of intraepidermal vesiculation include:
  •        Spongiosis: intercellular edema
  •        Ballooning: intracellular edema
  •        Acantholysis: loss of desmosomal attachments
  •        Cytolysis: cell disintegration
  •        Other types like epidermolytic hyperkeratosis

Several examples of common cutaneous blistering disorders are detailed in the table below.

Blistering Disorder
Key Clinical Features
Key Histologic Features
Hand, Foot, & Mouth Disease

·      May simulate irritant or toxic contact dermatitis
·      Important to distinguish from erythema multiforme and TEN: No interface changes or clinical features
·      Lancet shaped vesicles on acra & mucosa
·      Caused by Coxsackie virus A 5, 9, & 16
·      Recent isolation of aggressive form caused by A6 with extensive involvement, onychomadesis, & extensive mucosal erosions
·      Perivascular infiltrate of lymphocytes & some neutrophils
·      Ballooning degeneration of epidermis
Necrolytic Migratory Erythema
·      Widespread erosive dermatitis with abundant crusting
·      Glucagon secreting tumor of pancreas
·      Superficial epidermal pallor with ballooning
·      Psoriasiform dermatitis late
·      Infiltrate variable
·      Identical histology in other deficiency diseases, such as acrodermatitis enteropathica & biotin responsive multiple carboxylase deficiency
Hydroa Aestivale
·      Blisters & erosions of sun-exposed surfaces
·      Children most commonly affected
·      Scarring
·      Epidermal hyperplasia
·      Spongiosis & ballooning degeneration
·      Epidermal necrosis
Parapoxvirus Infection
·      Inflamed, boggy plaque usually on hands
·      Exposure to sheep or goats (orf) or cattle (milker’s nodule)
·      Marked epidermal hyperplasia
·      Intracellular edema; pink inclusions
·      Granulation tissue; edema in dermis
Epidermolytic Hyperkeratosis
·      Widespread erythema with vesiculation in infancy (congenital bullous ichthyosiform erythroderma)
·      Systemized verrucous epidermal nevus (ichthyosis hystrix)
·      Palmoplantar hyperkeratosis
·      Widespread or solitary keratotic papules (epidermolytic acanthoma)
·      Intraepidermal vacuolar degeneration
·      Pyknotic nuclei
·      Reddish-pink keratohyalin-like granules in epidermis
·      Hyperkeratosis; some parakeratosis
·      Keratin 10 gene mutation
Pemphigus Foliaceus
·      Erythema with erosions covered by exuberant crust
·      Scalp, face, trunk most  commonly involved Mucosal surfaces less commonly involved
·      Exfoliative dermatitis in
severe cases

·      Cleft in subcorneal, intragranular or upper spinous layer
·      Some dyskeratotic acantholytic keratinocytes in granular layer
·      Perivascular infiltrate of lymphocytes and eosinophils with exocytosis of eosinophils

Immunopathology
·      Direct IF: Intercellular IgG & C3 in epidermis in virtually 100% of cases; rarely IgA; slight accentuation in upper epidermis often
·      Indirect IF: Circulating antibodies to desmoglein 1 (160 kD desmosomal glycoprotein) in 33% & plakoglobin (85 kD adherens junction molecule) in higher percentage
·      Correlation between antibody titer & disease  activity variable & not always reliable
Pemphigus erythematosus (Senear-Usher)
·      Pemphigus foliaceus with features of systemic lupus erythematosus (SLE); +/- myasthenia gravis
·      Photosensitivity; positive ANA

·      Similar histology with vacuolar changes at DEJ

Solid clinicopathologic correlation is the key to making accurate diagnoses and initiating treatment for cutaneous blistering disorders.

References
Cockerell C (2015).  Cutaneous blistering disorders. [PowerPoint]

DermNet NZ (2015). Blistering skin diseases. Retrieved November 17, 2015, from http://dermnetnz.org/doctors/emergencies/blisters.html.


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