Page 166 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 5-3 Integumentary System

Autoantibody-mediated blisters:
BULLOUS PEMPHIGOID location of cleavage plane
PF (Dsg 1)
Bullous pemphigoid is the most frequently encountered
of all the autoimmune blistering diseases. It has a
characteristic clinical course and appearance. The
pathomechanism has been described in detail. The
cause is the formation of autoantibodies directed against BP, bullous pemphigoid;
two hemidesmosomal proteins, bullous pemphigoid Col VII, type VII collagen;
antigen 180 (BP180) and bullous pemphigoid antigen PV (Dsg 3) CP, cicatricial pemphigoid;
230 (BP230). These two proteins are critical for stabi- Dsg 1, desmoglein 1; Dsg 3,
lization of the hemidesmosomal plaque. If the hemides- desmoglein 3; EBA,
mosomal plaque is interrupted or destroyed, the end epidermolysis bullosa
result is subepidermal blistering of the skin. acquisita; HG, herpes
Clinical Findings: The hemidesmosomal plaque is gestationalis; PF, pemphigus
the main anchoring system of the dermal-epidermal BP (BP180, BP230) foliaceous; PV, pemphigus
junction. It is a complex apparatus with a multitude of CP, HG, LABD vulgaris; LABD, linear
proteins that interact to bind the epidermis to the immunoglobulin A
underlying dermis. If it is interrupted, the pemphigoid EBA (Col VII), LABD bullous dermatosis
complex of diseases may occur. These conditions
include bullous pemphigoid, herpes gestationis, and
cicatricial pemphigoid. Of these, bullous pemphigoid is
the disease state most frequently encountered. It most
commonly occurs in the fifth to seventh decades of life,
with no race or sex predilection.
Clinically, patients often have a prodrome of intensely
pruritic patches and plaques on the trunk, particularly
the abdomen. Soon thereafter, they begin to develop
large, tense bullae. The bullae can range from 1 cm to Tense bullae
10 cm in diameter, with an average of 2 cm. The blis- of bullous
ters are tense to palpation and are not easily ruptured. pemphigoid
If they do rupture, a fine, clear to slightly yellow serous
fluid drains, and the underlying dermis is exposed.
Reepithelialization is fairly rapid. Patients have con-
tinuous formation of new bullae, followed by healing
and then repetition of the blistering pattern, until treat-
ment is obtained. Scarring is minimal unless secondary
infection has occurred. Most patients with pemphigoid
do not have oral involvement, in direct contrast to those
with the pemphigus class of diseases.
Bullous pemphigoid can spontaneously remit and
relapse over time. Most patients seek therapy and are
treated with a host of agents. Patients typically respond
well to therapy and overall have an excellent prognosis.
Secondary infections and side effects from therapy can
lead to morbidity and mortality. Laboratory testing
reveals immunoglobulin G (IgG) antibodies against
BP180 or BP230 or both.
Pathogenesis: Bullous pemphigoid is caused by IgG Bullous pemphigoid. Subepidermal
autoantibody production. The two autoantibodies pro- blister cavity with multiple eosinophils
duced attack the BP180 and BP230 proteins, which are
integral components of the hemidesmosomal plaque.
BP180 is a transmembrane protein, and BP230 is an
intracellular protein that lies within the keratinocyte
and binds to BP180 and keratin filaments. The reason A generous shave biopsy,
for the development of these antibodies is unknown. sending the skin surrounding
Once they have formed, they attach to the hemidesmo- the blister for immunofluorscence
somal proteins. This activates a plethora of pathogenic staining, makes the diagnosis.
mechanisms that act to induce separation of the epider-
mis from the dermis. Critical in the pathogenesis is
activation of the complement cascade by the IgG anti-
bodies. Complement activation may lead to further complement C3 localize to the basement membrane Many patients are older and have comorbidities that
recruitment of inflammatory cells, which can be acti- zone and appear as a linear band. The salt-split skin must be taken into account. Mild, localized disease can
vated and thereafter release cytokines and enzymes that technique can also be used to differentiate the two dis- be treated with high-potency topical steroids. Severe
perpetuate the response. eases. This is achieved by incubating skin in a 1M NaCl disease is treated initially with oral steroids, and then
Histology: Routine hematoxylin and eosin staining solution to split the skin through the lamina lucida. the patient is transitioned to a steroid-sparing agent.
reveals a cell-poor subepidermal blister with scattered When immunofluorescence staining is used on salt-split The medications that have been routinely used include
eosinophils. The histological differential diagnosis can skin, the immunoreactants localize to the blister roof in mycophenolate mofetil, azathioprine, and the combina-
be between bullous pemphigoid and epidermolysis bullous pemphigoid and to the dermal base in EBA. tion of tetracycline and nicotinamide. Newer agents
bullosa acquisita (EBA). Immunofluorescence staining Treatment: The severity of bullous pemphigoid such as intravenous immunoglobulin (IVIG) have been
can be used to help differentiate the two. IgG and varies. Therapy needs to be tailored to the individual. used for severe refractory disease.

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