Skin inflammatory (nontumor)
Vesiculobullous and acantholytic reaction patterns
Bullous pemphigoid

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

Revised: 17 October 2018, last major update March 2017

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Skin [title] bullous pemphigoid

Cite this page: Grove, N. Bullous pemphigoid. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/skinnontumorbullouspemphigoid.html. Accessed December 12th, 2018.
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

Images hosted on other servers:

Subepidermal nonacantholytic blisters

Occurring after a burn

Postsurgical

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 description
  • 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:

Contributed by Dr. Angel Fernandez-Flores, Hospital El Bierzo & Clinica Ponferrada, Spain:

Subepidermal bullae



Images hosted on other servers:

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