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Developed in collaboration with the University of Auckland Goodfellow Unit in 2007.

Author: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, 2009.  

Images have been sourced from the following:

  • Hon Assoc Prof Amanda Oakley
  • The Department of Dermatology, Health Waikato
  • Prof Raimo Suhonen (Finland)
  • Arthur Ellis (medical artist)

 goodfellow unit logo

Blistering skin diseases CME


Created 2008.

Learning objectives


Blisters are accumulations of fluid within or under the epidermis. Diagnosis depends on the site of the intercellular split as shown in the table below.

Site of blisterCharacteristicsDifferential diagnosisImage
Subcorneal Very thin roof breaks easily Impetigo, miliaria, SSSS Miliaria
Intra-epidermal Thin roof ruptures to leave denuded surface Acute eczema, varicella, herpes simplex, pemphigus Eczema
Subepidermal Tense roof often remain intact Bullous pemphigoid, dermatitis herpetiformis, erythema multiforme, TEN, friction blisters Systemic lupus erythematosus
Systemic lupus erythematosus
Blisters and the site of intercellular split

SSSS: Staphylococcal scalded skin syndrome
TEN: Toxic epidermal necrolysis

Imherited blistering diseases

Epidermolysis bullosa (EB) refers to a group of inherited disorders in which there are mutations in specific keratin proteins (EB simplex), hemidesmosomes (junctional EB), anchoring filaments or type VII collagen (dystrophic EB). Minor trauma results in blisters and erosions, the split site and severity depending on the specific defect.

Immunobullous eruptions

There are at least 9 distinct immunobullous diseases due to autoantibodies directed at differing components of the desmosome complex. Skin biopsy and direct immunofluorescence are diagnostic and there may be detectable circulating skin antibodies. High dose corticosteroids and immunosuppressive medication may be required for control.

Bullous pemphigoid

Bullous pemphigoid is the most common immunobullous disease and affects the elderly. Early signs include various subacute itchy rashes on any site, particularly the flexures (submamammary, inguinal):

Eventually (days to weeks) the plaques evolve into subepidermal bullae, or these may arise from apparently normal skin.

Purulent lesions may or may not indicate secondary infection (staphylococcal and/or streptococcal), and in such cases spreading erythema may or may not be due to cellulitis.

Dermatitis herpetiformis

Dermatitis herpetiformis mostly affects young adults but may present at any age as a chronic prurigo. It mainly affects scalp, elbows, buttocks, knees and shoulders. Diagnosis is made by skin biopsy and rapid improvement on dapsone. Signs include:

Despite distressing itch, signs may be quite subtle (hence few photographs available!).

Dermatitis herpetiformis (DH) is associated with gluten-sensitive enteropathy in most cases (at least 85%) although this may be asymptomatic. Symptoms (in 10%) include:


Pemphigus has at least 7 subtypes caused by pathogenic IgG antibodies to intraepidermal cell adhesion molecules. It is diagnosed by clinical presentation and skin biopsy. The most common subtypes are:

Pemphigus vulgaris is potentially fatal; it usually presents with acute or subacute extensive oral ulceration followed by widespread cutaneous denudation. It appears to be particularly common in middle-aged patients from the Indian subcontinent.

Pemphigus foliaceus affects the elderly and presents with erosions affecting primarily seborrhoeic areas (scalp, face, chest). It is much less severe than pemphigus vulgaris.

Pemphigus may be precipitated by:

Other immunobullous diseases

Other rare immunobullous diseases include:


Skin biopsy and direct immunofluorescence (DIF) are crucial for diagnosis of immunobullous diseases.

DiseaseBiopsy featuresDIF
Bullous pemphigoid
  • Subepidermal oedema/blister
  • Mixed perivascular infiltrate with eosinophils
Linear IgG, C3 in BMZ (lamina lucida)
Dermatitis herpetiformis
  • Subepidermal vesicles
  • Mixed papillary infiltrate with eosinophils
Granular IgA in tips of papillae
Pemphigus vulgaris
  • Suprabasal acantholytic vesicle (tombstone pattern)
  • Mixed perivascular infiltrate with eosinophils
IgG within suprabasal intercellular spaces
Pemphigus foliaceus
  • Subcorneal acantholytic vesicle (tombstone pattern)
  • Mixed perivascular infiltrate with eosinophils
IgG within upper epidermal intercellular spaces
Paraneoplastic pemphigus
  • Suprabasal acantholytic vesicle (tombstone pattern)
  • Keratinocyte necrosis
  • Mixed perivascular infiltrate with eosinophils
IgG within epidermal intercellular spaces and BMZ
Pemphigoid gestationis
  • Spongiotic dermatitis
  • Subepidermal oedema/blister
  • Mixed perivascular infiltrate with eosinophils
Linear C3 in BMZ (lamina lucida)
Cicatricial pemphigoid
  • Subepidermal blister
  • Mixed perivascular infiltrate with plasma cells and eosinophils
Linear IgG, C3 in BMZ (lamina lucida)
Epidermolysis bullosa acquisita
  • Subepidermal blister
  • Sparse inflammatory infiltrate
Linear IgG, C3 in BMZ (upper dermis)
Linear IgA dermatosis
  • Subepidermal blister
  • Mixed papillary/perivascular infiltrate with eosinophils
Linear IgA, C3 in BMZ

BMZ: basement membrane zone
EM: electron microscopy

Other tests

Specific immunoreactive proteins detected using histochemistry on skin biopsies are beyond the scope of this article, and they are not evaluated in routine clinical practice.

There may be circulating ‘skin antibodies’ in immunobullous diseases. These are detected by indirect immunofluoresce of serum.

Dermatitis herpetiformis

Additional investigations to detect gluten enteropathy should include:


Dermatitis herpetiformis

Other immunobullous diseases

Control of immunobullous diseases can be very challenging and is best left to a dermatologist. Maintenance therapy is usually required for years if not lifelong and is likely to result in significant complications.


Describe the adverse effects of dapsone.

Related information


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