In pemphigus, autoantibodies form against desmoglein. Desmoglein forms the "glue" that attaches adjacent epidermal cells via attachment points called desmosomes. When autoantibodies attack desmogleins, the cells become separated from each other and the epidermis becomes "unglued", a phenomenon called acantholysis. This causes blisters that slough off and turn into sores. In some cases, these blisters can cover a significant area of the skin.
There are three types of pemphigus which vary in severity: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus.
* The most common form of the disorder is pemphigus vulgaris (PV - ICD-10 L10.0). It occurs when antibodies attack Desmoglein 3. Sores often originate in the mouth, making eating difficult and uncomfortable. Although pemphigus vulgaris may occur at any age, it is most common among people between the ages of 40 and 60. It is more frequent among ashkenazi Jews . Rarely, it is associated with myasthenia gravis.
* Pemphigus Foliaceus is the least severe of the three varieties. Desmoglein 1, the protein that is destroyed by the autoantibody, is only found in the top dry layer of the skin. Pemphigus foliaceus (PF) is characterized by crusty sores that often begin on the scalp, and may move to the chest, back, and face. Mouth sores do not occur. It is not as painful as pemphigus vulgaris, and is often mis-diagnosed as dermatitis or eczema.
* The least common and most severe type of pemphigus is paraneoplastic pemphigus (PNP). This disorder is a complication of cancer, usually lymphoma and Castleman's disease. It may precede the diagnosis of the tumor. Painful sores appear on the mouth, lips, and the esophagus. In this variety of pemphigus, the disease process often involves the lungs, causing Bronchiolitis obliterans (BOOP). Complete removal and/or cure of the tumor may improve the skin disease, but lung damage is generally irreversible .
Note that Haley-Haley disease, also called familial benign pemphigus, is an inherited (genetic) skin disease, not an autoimmune disease. It is therefore not considered part of the Pemphigus group of diseases.
Pemphigus is recognized by a dermatologist from the appareance and distribution of the skin lesions. Definitive diagnosis requires examination of a skin biopsy by a dermatopathologist. The skin biopsy is taken from the edge of a blister, prepared for histopathology and examined with a microscope. The pathologist looks for an intraepidermal vesicle caused by the breaking apart of epidermal cells (acantholysis). Thus, the superficial (upper) portion of the epidermis sloughs off, leaving the bottom layer of cells on the "floor" of the blister. This bottom layer of cells is said to have a "tombstone appearance".
Definitive diagnosis also requires the demonstration of anti-desmoglein autoantibodies by direct immunofluorescence on the skin biopsy. These antibodies appear as IgG deposits along the desmosomes between epidermal cells, a pattern reminiscent of chicken wire. Anti-desmoglein antibodies can also be detected in a blood sample using the ELISA technique. A high titre of cANCA (cellular Anti Neutrophil Cytoplasmic Antibody) is an important feature of the disease.
If not treated, pemphigus can be fatal due to overwhelming infection of the sores. The most common treatment is the administration of oral steroids, especially prednisone. The side effects of cortico-steroids may require the use of so-called steroid-sparing or adjuvant drugs. The immuno-suppressant CellCept (Mycophenolic acid) is among those being used.
Intravenous gamma globulin (IVIG) may be useful in severe cases, especially paraneoplastic pemphigus. Mild cases sometimes respond to the application of topical steroids. Recently, Rituximab, an anti-CD20 antibody, was found to improve otherwise untreatable severe cases of Pemphigus vulgaris.
All of these drugs may cause severe side effects, so the patient should be closely monitored by doctors. Once the outbreaks are under control, dosage is often reduced, to lessen side effects.
If paraneoplastic pemphigus is diagnosed with pulmonary disease, a powerful cocktail of immune suppressant drugs is sometimes used in an attempt to halt the rapid progression of bronchiolitis obliterans, including solumedrol, ciclosporin, azathioprine and thalidomide. Plasmapheresis may also be useful.
If skin lesions do become infected, antibiotic may be prescribed. In addition, talcum powder is helpful to prevent oozing sores from adhering to bedsheets and clothes.
Pemphigus in domestic animals
Pemphigus foliaceus has been recognized in pet dogs, cats and horses and is the most common autoimmune skin disease diagnosed in veterinary medicine. Pemphigus foliaceus in animals produces clusters of small vesicles that quickly evolve into pustules. Pustules may rupture, forming erosions or become crusted. Left untreated, pemphigus foliaceus in animals is life-threatening leading to loss of condition and secondary infection.
Pemphigus vulgaris is a very rare disorder described in pet dogs and cats. Paraneoplastic pemphigus has been identified in pet dogs.
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