Diseases and Conditions » Pemphigus

Pemphigus

Pemphigus is an autoimmune disorder that causes blistering and raw sores on skin and mucous membranes. As with other autoimmune disorders, it is caused when the body's defenses mistake its own tissues as foreign, and attack the cells. Pemphigus is derived from the Greek pemphix, meaning bubble or blister.

Introduction

Pemphigus is a group of rare skin disorders that cause blisters of your skin or mucous membranes, such as in your mouth or on your genitals.

Pemphigus usually occurs in people between the ages of 30 and 60, but it also can affect children and older adults. Men and women develop pemphigus equally, and it affects all races and cultures. However, pemphigus tends to be more common in people of Middle Eastern or Jewish descent.

Usually a chronic condition, pemphigus is best controlled by early diagnosis and treatment, which may include medications or treatments similar to those used for severe burns. Left untreated, pemphigus may be fatal.

Signs and symptoms

Pemphigus is characterized by blisters on your skin and mucous membranes. The blisters rupture easily, leaving open sores, which may ooze and become infected. The signs and symptoms of the three main types of pemphigus differ depending on the type:

• Pemphigus vulgaris. The most common form, pemphigus vulgaris usually begins with blisters in your mouth, which then erupt on your skin. Blisters also can break out on the mucous membranes of your genitals. The blisters typically are painful, but don't itch.
• Pemphigus foliaceus. This type doesn't usually affect mucous membranes. The blisters, which usually begin on your face and scalp and later erupt on your chest and back, usually aren't painful. They tend to be crusty and itchy.
• Paraneoplastic pemphigus. This form causes painful sores on your mouth and lips and in your esophagus, as well as skin lesions. This form of pemphigus also can cause lesions in your lungs, resulting in progressive lung disease and making it difficult for you to breathe (dyspnea).

Causes

The exact cause of pemphigus is unknown, but it may be an autoimmune disorder.

Normally, your immune system attacks foreign invaders, such as harmful viruses and bacteria. But in pemphigus, your immune system produces antibodies that attack healthy cells in your skin or mucous membranes, specifically proteins called desmogleins. Desmogleins bind skin cells to each other. The antibodies cause separation of the cells of the top layer of your skin (epidermis). This reaction is known as acantholysis.

Paraneoplastic pemphigus generally occurs in people who have cancer, most commonly non-Hodgkin's lymphoma and chronic lymphocytic leukemia. In cases in which the cancer hasn't yet been discovered, the appearance of pemphigus blisters may alert doctors to look for a malignancy.

Risk factors

Pemphigus isn't contagious, and there's no way to predict who'll get it. However, your risk increases if:

• You're between the ages of 30 and 60.
• You're of Mediterranean or Jewish descent.
• You have another autoimmune condition, particularly myasthenia gravis, a chronic disorder characterized by muscle weakness and fatigue, or thymoma, a tumor of the thymus. The thymus is an organ that produces white blood cells known as lymphocytes, an important part of your immune system.

Types

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 (ICD-10 L10.0). It occurs when antibodies attack Desmoglein 3, a protein that keeps cells bound together. Thus, cells simply fall apart, causing skin to slough off. Although pemphigus vulgaris may occur at any age, it is quite rare in children, and most common in the middle aged and elderly. Sores often originate in the mouth, making eating difficult and uncomfortable. Pemphigus vulgaris often affects people between the ages of 40-60, and mainly of Jewish or Mediterranean descent. Some patients are associated with myasthenia gravis, but it's unusual.

• Foliaceus is the least severe of the three varieties. Desmoglein 1, the protein that is destroyed by the body's immune system is only found in the top dry layer of the skin, so mouth sores do not occur. Pemphigus foliaceus is characterized by crusty sores that often begin on the scalp, and may move to the chest, back, and face. 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 the neoplastic variety, also known as paraneoplastic pemphigus. This disorder is usually found in conjunction with an already-existing malignancy. Very painful sores appear on the mouth, lips, and the esophagus. In this variety of pemphigus, the disease process often involves Bronchiolitis obliterans, a fatal destruction of alveoli in lung tissue. A diagnosis of neoplastic pemphigus may prompt a search for an existing tumor. Sometimes, the tumor is not malignant. In these cases, tumor removal may lead to a remission of the pemphigus. However, any decline in pulmonary function is generally irreversible. With Intravenous Immunoglobulin (IVIG) treatment and aggressive chemotherapy for the underlying lympoma, V Kingsley is now one known survivor of Paraneoplastic Pemphigus with pulmonary involvement (contact information in External Links below).

Diagnosis

Diagnosis relies on microscopic examination of skin lesion samples. A biopsy of a suspected lesion is taken: a sample of the blistered skin is removed and examined under the microscope to determine if the cells are separated in the manner characteristic of pemphigus. Unlike in the related pemphigoid, pemphigus manifests as intra-epithelial clefting, meaning the spinous cells of the epithelium break apart, a phenomenon known as acantholysis. This is because the desmosomes are attacked. In pemphigoid, the epitheium remains intact, but is entirely "unzipped" from the underlying connective tissue bed, or lamina propria, because the hemidesmosomes are attacked. Also apparent in pemphigus is a "tombstone appearance" of the basal cell layer and Tzanck cells.

Direct immunoflourescence on the biopsy skin sample can be used to detect desmoglein antibodies in the skin. The presence of these antibodies indicates pemphigus. Indirect immunofluorescence and ELISA can measure desmoglein antibodies in blood serum.

Treatment

If not treated, pemphigus is fatal, due to overwhelming systemic infection. The most common treatment is the administration of oral steroids, especially prednisone. Recently, there has been great promise of surviving some forms of pemphigus (especially PNP) by using a pooled blood product known as gamma globulin or IVIG. Mild cases sometimes respond to the application of topical steroids. 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 supressant drugs is sometimes used in an attempt to halt the rapid progression of bronchiolitis obliterans. Some drugs used include solumedrol, cyclosporin, azathioprine, and in rare instances, extremely controlled use of thalidomide in eligible patients. Immune phoresis procedures are also a possible treatment.

If skin lesions do become infected, antibiotics may be used for treatment. In addition, talcum powder is helpful to prevent oozing sores from adhering to bedsheets and clothes.

Treatment, which aims at reducing signs and symptoms and preventing complications, is most effective when it begins as early as possible. The less widespread pemphigus is, the easier it may be to control. Specific treatment methods depend on the severity of the disease.

• Mild pemphigus

If your pemphigus isn't too widespread, you may be able to remain at home for treatment. The mainstay of treatment is usually corticosteroids, such as prednisone. However, using corticosteroids over an extended time or in high doses may cause serious side effects, including:

• Weight gain
• Mood swings
• Elevated blood sugar (diabetes)
• Osteoporosis
• Redistribution of body fat, leading to a round face (moon face)
• Hair loss
• Increased chance of infection because of suppression of the immune system

Corticosteroids may be combined with other medications, including:

• Immunosuppressants. These medications, such as azathioprine (Imuran) or methotrexate (Rheumatrex), help keep your immune system from attacking healthy tissue. These drugs have serious side effects, including increased risk of infection.
• Antibiotics and antifungal medications. These may be prescribed to control or prevent infections.
• Severe pemphigus

Widespread pemphigus may require you to stay in the hospital, where you may receive treatment similar to treatment for severe burns. The open sores make you highly vulnerable to infection, which if it spreads to your bloodstream, may be fatal. Besides the medications listed above, you may be given:

• Fluids. Because you may have lost bodily fluids due to oozing of the sores, you may receive fluids through a vein (intravenously), as well as electrolytes — minerals such as sodium, potassium and calcium that maintain the balance of fluids in your body — and proteins.
• Intravenous feeding. This may be necessary if mouth sores make it painful for you to eat.
• Anesthetic mouth lozenges. These can help control pain of mild to moderate mouth sores.
• Therapeutic plasmapheresis. In this process, the fluid part of your blood, called plasma, is removed from blood cells by a device known as a cell separator. The purpose is to get rid of the antibodies that are attacking your skin. The plasma is replaced with donated plasma or intravenous fluids.