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.