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PEMPHIGUS
Pemphigus (pron.: /ˈpɛmfɪɡəs/ or /pɛmˈfaɪɡəs/) is a rare group of
blistering autoimmune diseases that affect the skin and mucous
membranes.
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.
Originally, the cause of this disease was unknown, and "pemphigus"
was used to refer to any blistering disease of the skin and mucosa. In
1964, a historic paper that changed the understanding of pemphigus
was published. In 1971, an article investigating the autoimmune
nature of this disease was published.
Types
There are several types of pemphigus which vary in severity:
pemphigus vulgaris, pemphigus foliaceus, Intraepidermal neutrophilic
IgA dermatosis, and paraneoplastic pemphigus.

Pemphigus vulgaris (PV - ICD-10 L10.0) is the most common
form of the disorder and 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. Nail disease may be the only finding and has prognostic
value in management]

Pemphigus foliaceus (PF) 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. 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.

Intraepidermal neutrophilic IgA dermatosis is characterized
histologically by intraepidermal bullae with neutrophils, some
eosinophils, and acantholysis.

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 (constrictive
bronchiolitis). Complete removal and/or cure of the tumor may
improve the skin disease, but lung damage is generally
irreversible .
Note that Hailey-Hailey 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.
Classification
Pemphigus is a group of autoimmune blistering diseases that may be
classified into the following types:
Pemphigus vulgaris, of which there several forms:

Pemphigus vegetans

Pemphigus vegetans of Hallopeau

Pemphigus vegetans of Neumann

Pemphigus foliaceus, of which there several forms:

Pemphigus erythematosus

Endemic pemphigus

Paraneoplastic pemphigus

IgA pemphigus, of which there several forms:

Subcorneal pustular dermatosis

Intraepidermal neutrophilic IgA dermatosis
Diagnosis
Pemphigus is recognized by a dermatologist from the appearance
and distribution of the skin lesions. It is also commonly diagnosed by
specialists practicing otolaryngology- head and neck surgery,
periodontists, oral and maxillofacial surgeons (highly specialized
surgeons with an extensive background and qualifications in both
medicine and dentistry), and eye doctors as lesions can affect the
eyes and mucous membrane of the oral cavity. Intraorally it
resembles the more common diseases lichen planus and mucous
membrane pemphigoid.[9] Definitive diagnosis requires examination
of a skin or mucous membrane biopsy by a dermatopathologist or
oral pathologist. 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 antidesmoglein 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.
Half of pemphigus patients have oral lesions alone during the first
year but develop skin lesions later.
Treatment
If not treated, pemphigus can be fatal from an overwhelming
infection of the sores. The most common treatment is the
administration of oral steroids, especially prednisone, often in high
doses. The side effects of corticosteroids may require the use of socalled steroid-sparing or adjuvant drugs. The immunosuppressant
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 antiCD20 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 methylprednisolone, ciclosporin, azathioprine, and
thalidomide. Plasmapheresis may also be useful.
If skin lesions do become infected, antibiotic may be prescribed.
Tetracycline antibiotics have a mildly beneficial effect on the disease
and are sometimes enough for Pemphigus Foliaceus. In addition,
talcum powder is helpful to prevent oozing sores from adhering to
bedsheets and clothes.
Pain is a common part of the disease.