Skin nontumor
Blistering disorders
Bullous pemphigoid

Author: Grove, Narine, M.D., (see Authors page)
Editor: Sara Shalin, M.D.

Revised: 22 March 2017, last major update March 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Skin [title] bullous pemphigoid

Cite this page: Bullous pemphigoid. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/skinnontumorbullouspemphigoid.html. Accessed May 23rd, 2017.
Definition / general
  • Common subepidermal, blistering, autoimmune disease of skin due to IgG antibodies to the hemidesmosomal antigens Bullous pemphigoid antigen 1 and 2
  • Patients present with tense bullae, which do not rupture easily, on an erythematous base
Essential features
  • Subepidermal blister with eosinophils and superficial dermal edema
  • Direct immunofluorescence (DIF): linear IgG (usually IgG4) and complement deposits at the basement membrane zone with n-serrated pattern
  • Primarily in the elderly
  • Treatment includes steroids (topical or systemic), tetracycline, immunosuppressives and IVIG infusions for steroid resistant disease (J Dermatol Sci 2017;85:77)
Epidemiology
  • Incidence of 10 - 15 new cases per million people per year (J Dtsch Dermatol Ges 2009;7:434, Br J Dermatol 2009;161:861), but depends on age of population since incidence significantly increases after age 70 years
  • Accounts for 80% of subepidermal autoimmune bullous diseases
  • Occurs primarily in the elderly
  • Childhood bullous pemphoigoid: may affect infants, may be localized to vulva in girls
Etiology
Diagrams / tables
Images hosted on other servers:

Mechanisms of blister formation

University of Oulu, Finland

Clinical features
  • Multiple tense bullae of different sizes on flexor surfaces, trunk, intertriginous regions and mucosa
  • Bullae don't rupture easily and heal without scarring
  • Can develop on normal or erythematous skin
  • Oral lesions present in 10% - 40%
  • May flare up after years without symptoms
Treatment
  • Medications include steroids (topical or systemic), tetracycline, immunosuppressives and IVIG infusions for steroid resistant disease (J Dermatol Sci 2017;85:77)
  • Systemic corticosteroid dose should be kept low in the elderly
Clinical images
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Subepidermal nonacantholytic blisters

Occurring after a burn

Post surgical

Microscopic (histologic) description
  • Unilocular, subepidermal, nonacantholytic blisters with festooning (suspended in a loop between two points) of dermal papillae, infiltrate including eosinophils located in blister cavity and in the dermis
  • Early erythematous lesion shows upper papillary dermal edema, perivascular lymphohistiocytic infiltrate, accompanied by conspicuous eosinophils
  • If the biopsy is taken from an erythematous area, it will show more intense dermal eosinophilic infiltrate vs when the biopsy is taken from a bulla on otherwise normal skin
  • Mild interface changes can be seen in early or prodromal lesions
  • In established lesion, the changes are mostly inflammatory cell rich, may become neutrophil-rich
  • Eosinophilic microabscesses and rarely neutrophilic microabscess are seen
  • Eosinophilic spongiosis may be seen in clinically erythematous skin bordering the lesion
  • Eosinophilic "flame figures" can be rarely seen
Immunofluorescence
  • Linear deposition of IgG and C3 along the basement membrane zone; if blister is present on immunofluorescence biopsy, immunoreactants will deposit on roof of the blister (epidermal side)
  • n-serrated pattern on immunofluorescence vs u-serrated in Epidermolysis Bullosa Acquisita (EBA) (Br J Dermatol 2004;151:112)
  • Immunohistochemistry is not as sensitive as direct immunofluorescence in diagnosis of BP (Br J Dermatol 2016;175:988)
  • IgM and IgA present in 20% of the cases, IgA is more associated with mucosal involvement
  • Indirect immunofluorescence (salt split skin): patient serum is applied to substrate skin with blister induced by 1 M NaCl → autoantibodies bind to the roof of the blister
Microscopic (histologic) images
Images hosted on PathOut server:

Subepidermal bullae - contributed by Dr. Angel Fernandez-Flores, Hospital El Bierzo & Clinica Ponferrada, Spain



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Eosinophilic infiltrate

Subepidermal bullae

Subepidermal blister and dermal inflammation

Subepidermal blister, numerous eosinophils in edematous dermis

Subepidermal blister, polymorphous inflammatory infiltrate

Superficial perivascular inflammation

Superficial inflammation with numerous eosinophils. Early cleft formation

Type IV collagen on blister floor



Linear deposition of IgG in direct immunofluorescence

Indirect immunofluorescence study on salt-split normal human skin substrate
with the serum from a patient with bullous pemphigoid detects IgG serum autoantibodies
that bind to the epidermal (roof) side of the skin basement membrane

Positive stains
  • Direct immunofluorescence: linear IgG and C3 antibodies to hemidesmosomes at lamina lucida of basement membrane (versus granular pattern for discoid lupus), occasional IgA and IgM
  • 70% have circulating antibodies that bind to basement membrane of normal skin or mucous membranes
  • Antibodies bind to epidermal side in salt split skin test
  • Antibodies on formalin fixed paraffin embedded tissue less sensitive
  • Type IV collagen can be detected on blister floor (in contrast to EBA)
Differential diagnosis
  • Early lesions can resemble urticaria
  • Antiepiligrin cicatricial pemphigoid: usually affects mucus membranes, reactivity on dermal side (blister floor) in salt split skin test
  • Pemphigoid gestationis
  • Epidermolysis bullosa acquisita (EBA): reactivity on dermal side in salt split skin, fluorescence on the floor of the blister, while BP fluorescence is on the roof of the blister
  • Bullous lupus erythematosus: fulfills criteria for SLE, including positive lupus serology (antinuclear antibodies); reactivity on dermal side in salt split skin
  • Dermatitis herpetiformis: papillary neutrophilic microabscesses, basal cell vacuoles, granular IgA pattern in dermal papillae by direct immunofluorescence, no circulating antibodies