Skin-nontumor / clinical dermatology
Blistering disorders
General

Authors: Narina Grove, M.D., M.A. (see Authors page)
Editors: Sara Shalin, M.D., Ph.D.

Revised: 26 September 2016, last major update September 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Blistering disorders [title]

Cite this page: Blistering disorders - General. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/skinnontumorblisteringgeneral.html. Accessed December 4th, 2016.
Definition / General
  • Heterogeneous group of disorders affecting the skin or mucous membranes
  • Blisters are fluid filled cavities within or beneath the epidermis
  • Vesicles are 0.5 cm or less; bullae are greater than 0.5 cm
  • Definitive diagnosis requires clinical information
  • Large intraepidermal bullae without acantholysis may represent healed subepidermal bullae (re-epitheliazation phenomemon)
  • Blisters can be a result of spongiotic or lichenoid inflammatory reaction patterns, infection, autoimmune mediated processes, inherited / genetic mutations, paraneoplastic, drug and physical injury / external alterations
  • Blisters are categorized broadly into subcorneal, intraepidermal and subepidermal, based on location of the dermal / epidermal split
ICD-10 coding
Epidemiology
  • Any age, gender and race
  • Wide variety of clinical settings including autoimmune disorders, drug reactions, infections, genetic disorders and physical injury
  • Specific types of blistering disorders have predilection for certain population groups
  • Any site can be affected
Pathophysiology
Diagrams / Tables

Images hosted on other servers:

Layers of skin

Numerous proteins make up the basement membrane zone; mutations in any of them can cause blistering, and any protein can be a target for autoimmune mediated blistering syndromes

Diagnosis
  • Clinical:
    • Lesion distribution (including presence or absence of mucosal lesions)
    • History and demographic information
    • Tense vs flaccid blisters can help signify at what level of skin the blister is occurring
    • See clinical algorithm for diagnosing blistering diseases
    • Nikolsky sign: elicitation of blistering by gentle mechanical pressure on the skin (J Am Acad Dermatol 2006;54:411); generally signifies a superficial blistering process (i.e. pemphigus)

  • Skin biopsy:
    • Edge of the lesion should be biopsied and submitted in formalin for H&E evaluation (Cutis 2015;95:237)
    • Second biopsy should be taken from perilesional skin that is clinically normal and submitted in Michel's solution if there is concern for an autoimmune mediated blistering disorder
    • Histologic evaluation must include:
      • Plane of separation (where is the blister ocurring?)
      • Presence or absence of acantholysis
      • Characterization of any associated inflammatory infiltrate
      • Immunofluorescent pattern

  • Direct Immunofluorescence (DIF):
    • Useful in the distinction of immune mediated vs. non immune mediated blistering disorders
    • Requires submission in Michel's solution (preserves protein antigenicity without fixing the tissue)
    • Currently almost always performed on frozen tissue sections

  • Reactants and patterns of deposition:
    • IgG and C3 (pemphigus foliaceus, pemphigus vulgaris, pemphigus vegetans, paraneoplastic pemphigus, epidermolysis bullosa acquisita; bullous pemphigoid, Indian J Dermatol 2016;61:288)
      • Linear deposition along basement membrane zone: epidermolysis bullosa acquisita, bullous pemphigoid
      • Intercellular deposition: pemphigus family of diseases
    • IgA (linear IgA, dermatitis herpetiformis, Am J Dermatopathol 2016;38:283)
      • Linear deposition along basement membrane zone: linear IgA bullous dermatosis
      • Granular deposition along basement membrane zone: dermatitis herpetiformis
    • IgM and C3 (porphyria cutanea tarda, erythema multiforme)
      • Perivascular deposition: porphyria cutanea tarda
      • Globular deposits in papillary dermis: erythema multiforme
    • DIF negative (Sneddon-Wilkinson, AGEP, SSSS, Hailey-Hailey, Darier's, Grover's, TEN / SJS, infections such as herpes, impetigo)

  • Laboratory:
    • Indirect immunofluorescence: utilization of skin substrate (usually non-human) incubated with patient serum to determine pattern of autoantibody deposition
      • Provides a titer of autoantibodies, which (especially in pemphigus) correlates with disease activity
    • Antigen specific serologic testing

  • Basement membrane zone salt-split skin technique:
    • Test of choice to differentiate between subtypes of autoimmune bullous diseases with autoantibodies directed against proteins of the dermoepidermal basement membrane zone (Dermatol Clin 2011;29:365)
    • Indirect test performed by incubating normal skin substrate in hypertonic saline (which induces a subepidermal blister) followed by application of patient serum to see where autoantibodies bind (roof = bullous pemphigoid, floor = epidermolysis bullosa acquisita)
Case Reports
Treatment
  • Antibiotics or antivirals for infectious etiologies
  • Topical corticosteroids
  • Systemic glucocorticoids
  • Immunosuppressive therapy
  • Anti-inflammatory therapy
  • Intravenous immunoglobulin
  • Reference: Dermatol Clin 2016;34:251
Micro Description
  • May or may not contain a blister (separation of the layers of the skin)
  • If blister present, may be subcorneal, intraepidermal (suprabasilar) or subepidermal
  • Level and content of inflammation varies
Micro Images

Images hosted on PathOut server:

Contributed by Dr. J. Taube, Johns Hopkins University, Maryland (USA):

Bullous pemphigoid (H&E); note eosinophils within the blister



Images hosted on other servers:

Hailey-Hailey (H&E)

Pemphigus foliaceous (H&E)



For more images please see condition specific pages.
Electron Microscopy Description
  • Electron microscopy may be useful for determining the exact level of blister split, particularly in cases of inherited blistering disorders
    • May distinguish between epidermolysis bullosa simplex vs junctional epidermolysis bullosa vs dystrophic epidermolysis bullosa vs other variants
Molecular / Cytogenetics Description
  • Generally not applicable