An Overview of Pemphigus

An Autoimmune Disorder Characterized by Painful Blistering

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public domain photo of pemphigus (circa 1886)

George Henry Fox (1886) 

Pemphigus is a rare group of blistering autoimmune diseases that affects both the skin and mucous membranes. The name is derived from the Latin word pemphix meaning "pus-filled blister." Originally, pemphigus was used to describe any blistering skin condition but was changed in the 1970s to describe blistering diseases that were autoimmune in nature.

Why pemphigus occurs remains something of a mystery, but scientists have been able to establish that the immune system will suddenly target and attack proteins, called desmoglein, that help cells stick together.

Pemphigus can occur on its own or manifest as a feature of certain autoimmune diseases or cancers. Pemphigus may also be triggered by certain drugs. The diagnosis typically involves a biopsy of the skin or mucous membrane. Treatment may include oral or injected steroids, immunosuppressant medications, intravenous antibodies, and biologic drugs.

Before the advent of corticosteroids, the rate of mortality in people with pemphigus was around 70 percent within a year. Even today, the death rate hovers at between 10 and 15 percent.

Symptoms

Pemphigus will generally affect mucosal membranes of the mouth first, causing multiple ulcers that can persist for weeks and months. In some cases, the oral lesions may be the only symptom. In others, blisters may develop on the skin, most predominately the upper chest, back, scalp, and face.

The blisters are generally ill-defined and easily ruptured. They will often consolidate into larger blisters and cause extensive peeling and oozing. The blisters are almost invariably painful, and, depending on their location, can be itchy or non-itchy.

If left untreated, pemphigus can gradually spread and involve greater amounts of tissue. This can lead to potentially life-threatening complications, including:

Death is most often the result of septicemia, infection, or pneumonia.

Types

There are several types of pemphigus that vary in their severity. The two main types are differentiated by the depth of the lesions as well as their locations on the body.

Pemphigus Vulgaris

Pemphigus vulgaris is the most common form of the disease. The sores most always originate in the mouth but may also affect other mucosal tissues, including the esophagus, labia, vagina, cervix, vulva, penis, urethra, anus, nasal passages, and conjunctiva of the eye.

Because the disease affects deeper tissues, the blisters can be extremely painful (although they tend not to itch). Only a small percentage of people will develop skin blisters as well.

Pemphigus vulgaris can sometimes occur as a feature of the neuromuscular autoimmune disease myasthenia gravis.

Pemphigus Foliaceus

Pemphigus foliaceus is a less severe form of the disease affecting the skin. It only involves superficial tissues on the dry top layer known as the stratum corneum. Because of this, the disease is far less painful but can often be extremely itchy.

Pemphigus foliaceus is characterized by crusty sores that often develop on the scalp and spread to the chest, back, and face. Mouth sores do not occur.

Pemphigus foliaceus can sometimes affect people with psoriasis, most often as a result of ultraviolet (UV) light therapy used to treat the autoimmune skin condition.

Other Types

There are other less common but potentially more serious forms of pemphigus, each of which has different underlying causes:

  • Immunoglobulin A (IgA) pemphigus is caused by a different antibody than that associated with pemphigus vulgaris or foliaceus. It can sometimes cause pus-filled lesions (pustules) but is considered the least serious form overall.
  • Pemphigus vegetans causes thick sores under the arms and in the groin. It can often develop in people who are resistant to pemphigus drug treatments.
  • Paraneoplastic pemphigus is a rare but potentially life-threatening complication of certain cancers, including lymphoma and Castleman's disease. It can cause ulcers on the lips, mouth, eyelids, and airways. If left untreated, the disease can cause irreversible lung damage and even death.

Hailey-Hailey disease, also known as familial benign pemphigus, is an inherited skin disorder and not an autoimmune disease. Despite its name, it is neither classified as pemphigus nor treated as such.

Causes

As an autoimmune disease, pemphigus is characterized by an immune system gone awry. For reasons poorly understood, the body will suddenly turn its immune defenses on normal cells as if to neutralize an infection.

With pemphigus, the immune system will produce proteins called autoantibodies that are programmed to target desmoglein. Desmoglein is a protein that functions as an adhesion molecule, holding cells together to maintain tissue integrity.

The inflammation caused by pemphigus breaks the bonds between skin cells, causing delamination (acantholysis) and the build-up of lymph fluid between the tissue layers.

With the exception of IgA pemphigus, the autoantibodies involved in pemphigus are immunoglobulin G (IgG). Certain types will target desmoglein 1 in superficial tissues (causing pemphigus foliaceus), while others will target desmoglein 3 in deeper tissues (causing pemphigus vulgaris).

Genetics

Genetics is believed to play a central role in the development of pemphigus. Certain genetic mutations are commonly seen in people with the disease, most of which involve the human leukocyte antigen (HLA) group of genes. HLA DR4 is the mutation most commonly seen in people with pemphigus.

Pemphigus disproportionately affected certain ethnic groups, including Ashkenazi Jews and people of Mediterranean origin. There are even certain subtypes that occur almost exclusively in Colombian and Tunisian populations.

Risk Factors

Pemphigus affects men and women equally. It generally occurs between the ages of 30 and 60. While genetics may predispose a person to pemphigus, the actual symptoms are believed to be activated by environmental triggers, the most common of which include:

  • Extreme emotional stress
  • Excessive exposure to UV radiation, including sunlight and phototherapy
  • Skin trauma, such as abrasions, cuts, sunburn, insect bites, and radiation therapy
  • Certain medications, especially penicillin, penicillamine, cephalosporin, Capoten (captopril), and Vasotec (enalapril)

Despite the long list of known triggers, the majority of cases will be idiopathic (meaning of no known origin).

Diagnosis

Pemphigus can mimic other diseases and usually requires a specialist, such as dermapathologist or oral pathologist, to render a definitive diagnosis. This typically involves a biopsy of the affected skin or mucosal tissues.

Under the microscope, the pathologist will look for fluid-filled lesions in the outer layer of skin (called intraepidermal vesicles). The vesicles provide clear evidence of acantholysis and help differentiate pemphigus from other blistering skin diseases.

A definitive diagnosis requires a technique known as direct immunofluorescence to identify anti-desmoglein autoantibodies. Under the microscope, the autoantibodies will appear as fluorescent deposits in the junctions between cells.

A blood test, referred to as an enzyme-linked immunosorbent assay (ELISA), can also be used to detect anti-desmoglein autoantibodies.

If the esophagus is affected, an endoscopy may be performed to view inside the windpipe and obtain tissue samples. X-ray and ultrasound are less helpful in rendering a diagnosis.

Differential Diagnosis

If the results are inconclusive, the doctor will look for other possible causes of the symptoms. Referred to as a differential diagnosis, the investigation may include such diseases as:

Treatment

If not treated immediately, pemphigus can be fatal, usually as the result of overwhelming opportunistic infections. Because of this, pemphigus may require hospitalization and involve many of the same interventions used in burn centers.

The mainstay of pemphigus treatment is oral corticosteroids, usually prednisone. This typically requires extremely high doses, which can be dangerous for some, causing intestinal perforation and sepsis.

The problem can be further exacerbated by nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat pain. NSAIDs can cause gastrointestinal bleeding and may increase the risk of perforation.

If oral corticosteroids cannot be used, other options may be considered, including:

Plasmapheresis, a technique similar to dialysis used to clean blood, may be considered if Rituxan cannot be used. Tetracycline antibiotics may also be prescribed to prevent secondary infections, while talcum powder can prevent bedsheets and clothing from sticking to the lesions.

Many people get better with treatment, although it can sometimes take years to fully recover. Others will need to take medications permanently to prevent a recurrence.

Coping

Given that we know so little about what triggers pemphigus, it's hard to suggest what you can do to avoid it if you have never had it before. With that being said, you may be able to prevent recurrence if you've had pemphigus in the past. Here are some self-help tips that can help:

Pemphigus may be difficult to live with, especially if it affects your ability to eat, causes pains, or creates unsightly, oozing sores. Rather than isolating yourself, it helps to speak with others who understand what you are going through.

You can connect with online support communities on Facebook or contact the non-profit International Pemphigus and Pemphigoid Foundation to see if there is a support group in your area.

If you are unable to cope, do not hesitate to ask your doctor for a referral to a therapist or psychiatrist who can provide counseling and medications, if needed.

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