Skin nontumor
Vesiculobullous and acantholytic reaction patterns
Bullous pemphigoid
Topic Completed: 1 March 2017
Minor changes: 23 July 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Skin [title] bullous pemphigoid
Table of Contents
Definition / general | Essential features | Epidemiology | Etiology | Clinical features | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Immunofluorescence description | Immunofluorescence images | Positive stains | Differential diagnosisCite this page: Grove N, Shalin SC. Bullous pemphigoid. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumorbullouspemphigoid.html. Accessed September 18th, 2020.
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
- Autoantibodies generated against BP1 antigen (230 kD, hemidesmosome desmoplakin 1 and 2) and BP2 antigen (180 kD type XVII collagen), both hemidesmosome and lamina lucida) (Rapini: Practical Dermatology, 2nd Edition, 2012)
- Emerging side effect associated with the use of checkpoint inhibitors:
- Pembrolizumab associated BP (Clin Exp Dermatol 2017;42:309)
- Nivolumab associated BP (J Eur Acad Dermatol Venereol 2017;31:e349, JAAD Case Rep 2016;2:442)
- Can be induced by other medications:
- Efalizumab (anti-CD11a, Dermatology 2009;219:89), Etanercept (TNF-alpha blocker, Dermatology 2009;219:357), Gabapentin (for neuropathic pain, J Am Osteopath Assoc 2017;117:191), Ustekinumab (anti IL12 / IL23, Eur J Dermatol 2017;27:81)
- Cases of postviral and postimmunization BP have been reported in pediatric population (BMC Pediatr 2017;17:60)
- Rarely occurs due to trauma (Indian J Dermatol Venereol Leprol 2009;75:617)
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
Microscopic (histologic) images
Contributed by Angel Fernandez-Flores, M.D., Ph.D.
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
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
Immunofluorescence images
Images hosted on other servers:
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
