BULLOUS PEMPHIGOID
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 two hemidesmosomal proteins, bullous pemphigoid antigen 180 (BP180) and bullous pemphigoid antigen 230 (BP230). These two proteins are critical for stabilization of the hemidesmosomal plaque. If the hemidesmosomal plaque is interrupted or destroyed, the end result is subepidermal blistering of the skin.
Clinical
Findings: The hemidesmosomal plaque is the main anchoring system of the
dermal-epidermal junction. It is a complex apparatus with a multitude of
proteins that interact to bind the epidermis to the underlying dermis. If it is
interrupted, the pemphigoid 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 10 cm in diameter, with an
average of 2 cm. The blisters are tense to palpation and are not easily
ruptured. 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 continuous formation of new bullae, followed by healing
and then repetition of the blistering pattern, until treatment 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 autoantibody production. The two autoantibodies
produced 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 for the development of these antibodies is
unknown. Once they have formed, they attach to the hemidesmosomal proteins.
This activates a plethora of pathogenic mechanisms that act to induce
separation of the epidermis from the dermis. Critical in the pathogenesis is
activation of the complement cascade by the IgG anti-bodies. Complement
activation may lead to further recruitment of inflammatory cells, which can be
activated and thereafter release cytokines and enzymes that perpetuate the
response.
Histology:
Routine
hematoxylin and eosin staining reveals a cell-poor subepidermal blister with
scattered eosinophils. The
histological differential diagnosis can be between bullous pemphigoid and
epidermolysis bullosa acquisita (EBA). Immunofluorescence staining can be used
to help differentiate the two. IgG and complement C3 localize to the basement membrane zone and appear as a
linear band. The salt-split skin technique can also be used to differentiate
the two diseases. This is achieved by incubating skin in a 1M NaCl solution to
split the skin through the lamina lucida. When immunofluorescence staining is used
on salt-split skin, the immunoreactants localize to the blister roof in bullous
pemphigoid and to the dermal base in EBA.
Treatment:
The
severity of bullous pemphigoid varies. Therapy needs to be tailored to the
individual. Many patients are older
and have comorbidities that must be taken into account. Mild, localized disease
can be treated with high-potency topical steroids. Severe disease is treated
initially with oral steroids, and then the patient is transitioned to a
steroid-sparing agent. The medications that have been routinely used include
mycophenolate mofetil, azathioprine, and the combination of tetracycline and
nicotinamide. Newer agents such as intravenous immunoglobulin (IVIG) have been used for severe
refractory disease.
