PEMPHIGUS VULGARIS
Pemphigus vulgaris is the prototypical acantholytic autoimmune blistering disease. It is one of the most serious of all blistering diseases. Blister formation in this subset of skin diseases occurs secondary to intraepidermal acantholysis. The desmosomal plaque is the target of the autoantibodies found in this disease.
Clinical Findings: The mean age at onset is approximately 55 years. Patients present with
rapid onset of vesicles and bullae that rupture easily. The flaccid bullae are
rarely found intact. The disease often begins within the oral cavity, and the
oral lesions can either precede the skin disease or occur independently of skin
manifestations. Vesicles and bullae are almost never seen in the oral cavity,
because the blisters in pemphigus are superficial and rupture almost
immediately after they are formed. The oral erosions are excruciatingly painful
and are frequently misdiagnosed as a herpes simplex infection. Often, it is not
until the erosions become chronic that the diagnosis of pemphigus is
entertained. Patients eventually avoid eating because of the pain, and they
often complain of weight loss, fatigue, and malaise.
If skin lesions are also present, the diagnosis can be made with more confidence based on the clinical
findings. However, one must perform a biopsy to rule out the other pemphigus
variants. Paraneoplastic pemphigus always starts in the mouth and tends to be
much more severe and refractory to therapy than pemphigus vulgaris. This
diagnosis should be considered in a patient who has a coexisting malignancy and
treatment-refractory disease. Immunoblotting is a specific test to look for the
exact autoantibody present in paraneoplastic pemphigus; it can be performed in
highly specialized laboratories. In pemphigus vulgaris, indirect immuno-fluorescence
almost always shows a high titer against desmoglein 3. The antibody titer
correlates with the disease activity, and titers have been monitored to assess
the treatment of the disease. Pruritus is uncommon in patients with pemphigus;
the overwhelming complaint is skin pain. If left untreated, the disease is
progressive and carries a mortality rate of 60% to 65%.
The skin blisters of pemphigus vulgaris rupture early
in the course of their formation. The remaining erosions can become quite
large, however. Weeping of serous fluid is present, and bleeding from the
erosions can also be seen. Secondary superinfection is common and may cause an
increase in autoantibody production.
Pathogenesis: Pemphigus
vulgaris is a chronic autoimmune blistering disease in which autoantibodies are
directed against the desmosomal plaque. The desmosomal plaque is the most
crucial element that holds adjacent keratinocytes in place and juxtaposed to
one another. There are other intercellular connections between keratinocytes,
including gap junctions, adherens junctions, and tight junctions. The
desmosomal plaque is
composed of various proteins that act to connect the intracellular actin
cytoskeleton of one keratinocyte to that of another; these include various
desmoglein, desmocollin, desmoplakin, plakophilin, and plakoglobin proteins.
The central portion of the desmosome contains the proteins desmoglein and
desmocollin. They are responsible for the tight binding of adjacent
keratinocytes. There are many members in each of the desmoglein and desmocollin
families.
Autoantibodies to the desmoglein family of proteins,
specifically desmoglein 3, are responsible for the formation of pemphigus
vulgaris. Antibodies against desmoglein 1 have also been found in patients with
pemphigus vulgaris and pemphigus foliaceous.
Histology: Skin biopsies
of pemphigus vulgaris shows intraepidermal blister formation. The blisters are
formed by acantholysis, and keratinocytes appear to be free floating within the
blister cavity. “Tombstoning” may be present. This is the designation given to
the basilar keratinocytes that stay
attached to the basement membrane zone by their unaffected hemidesmosomes. The
basilar keratinocytes appear to be standing up in a row, mimicking tombstones.
Immunofluorescence show immunoglobulin G staining in a fishnet pattern
throughout the epidermis. Each intercellular connection between keratinocytes
is highlighted.
Treatment: Appropriate
therapy needs to be instituted as soon as the diagnosis is made. High-dose oral
or intravenous corticosteroids have been the mainstay of therapy. However,
patients need to be transitioned to a steroid-sparing agent. Many
immunosuppressive medications have been used to treat pemphigus vulgaris. The
more common ones are azathioprine, myco- phenolate mofetil, cyclophosphamide,
and the newer agents, intravenous immunoglobulin (IVIG) and rituximab.
Morbidity and mortality have been dramatically reduced since t e introduction
of steroids and steroid-sparing agents.
