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Online version updated August 2011
Questions and Answers about Pemphigus
This booklet contains general information about pemphigus. It describes what pemphigus is and how it is diagnosed and treated. At the end is a list of key words to help you understand the medical terms used in this booklet. If you have further questions after reading this booklet, you may wish to discuss them with your doctor.
What Is Pemphigus?
Pemphigus is a group of rare autoimmune diseases that cause blistering of the skin and mucous membranes (mouth, nose, throat, eyes, and genitals). Some forms of the disease, including the most common form, may be fatal if left untreated.
Normally, our immune system produces antibodies that attack viruses and harmful bacteria to keep us healthy. In people with pemphigus, however, the immune system mistakenly attacks the cells in the epidermis, or top layer of the skin, and the mucous membranes. The immune system produces antibodies against proteins in the skin known as desmogleins. These proteins form the glue that keeps skin cells attached and the skin intact. When desmogleins are attacked, skin cells separate from each other and fluid can collect between the layers of skin, forming blisters that do not heal. In some cases, these blisters can cover a large area of skin.
It is unclear what triggers the disease, although it appears that some people have a genetic susceptibility. Environmental agents may trigger the development of pemphigus in people who are likely to be affected by the disease because of their genes. In rare cases, it may be triggered by certain medications. In those cases, the disease usually goes away when the medication is stopped.
Pemphigus is not contagious. It does not spread from person to person.
Though there can be a genetic predisposition to develop pemphigus, there is no indication that the disease is hereditary.
Pemphigus affects people across racial and ethnic lines. Research has shown that certain ethnic groups (such as the eastern European Jewish community and people of Mediterranean descent) are more susceptible to pemphigus. A particular type of pemphigus occurs more frequently in people who live in the rain forests of Brazil.
Men and women are equally affected. Research studies suggest a genetic predisposition to the disease. Although the onset usually occurs in middle-aged and older adults, all forms of the disease may occur in young adults and children.
There are several types of pemphigus and other similar blistering disorders. The type of disease depends on what layer in the skin the blisters form and where they are located on the body. Blisters always occur on or near the surface of the skin, which is called the epidermis. People with pemphigus vulgaris, for example, have blisters that occur within the lower layer of the epidermis, while people with pemphigus foliaceus have blisters that form in the topmost layer. The type of antibody that is attacking the skin cells may also define the type of disease present.
- Pemphigus vulgaris is the most common type of pemphigus in the United States. Soft and limp blisters appear on healthy-looking skin and mucous membranes. The sores almost always start in the mouth. The blisters of pemphigus vulgaris form within the deep layer of the epidermis, and are often painful. Blistered skin becomes so fragile that it may peel off by rubbing a finger on it. The blisters normally heal without scarring, but pigmented spots (spots where skin appears darker than the surrounding skin) may remain for a number of months.
- Pemphigus vegetans is a form of pemphigus with thick sores in the groin and under the arms.
- Pemphigus foliaceus involves crusted sores or fragile blisters that often appear first on the face and scalp and later on the chest and other parts of the body. Unlike pemphigus vulgaris, blisters do not form in the mouth. The sores are superficial and often itchy, and are rarely as painful as pemphigus vulgaris blisters. There may also be loose, moist scales on the skin.
- IgA pemphigus is a blistering disorder in which a different type of antibody binds to the cell surface of epidermal cells. This disease is different from other forms of pemphigus because it involves a different type of antibody (called IgA) than other types. The disease may result in blisters similar to those seen in pemphigus foliaceus, or it may involve many small bumps containing pus. This is the most benign, or least harmful, form of pemphigus.
- Paraneoplastic pemphigus is a rare disease that is distinct from pemphigus, but shares some features of it. It occurs in people with certain types of cancer, including some lymphomas and leukemias. It often involves severe ulcers of the mouth and lips, cuts and scarring of the lining of the eye and eyelids, and skin blisters. Because the antibodies also target the membranes lining the airways, patients may develop life-threatening problems in the lungs. This disease is different from pemphigus, and the antibodies in the blood are different. Special tests may be needed to identify paraneoplastic pemphigus.
Pemphigoid is also a blistering disorder caused by autoimmune problems that result in an attack on the skin cells by a person’s own antibodies. Pemphigoid produces a split in the cells where the epidermis and the dermis (the layer below the epidermis) meet, causing deep, tense (taut or rigid) blisters that do not break easily. Pemphigus, on the other hand, causes a separation within the epidermis, and the blisters are soft, limp, and easily broken. Pemphigoid is seen most often in the elderly and may be fatal. Usually, both pemphigus and pemphigoid are treated with similar medications. Severe cases may require different treatment.
A diagnosis of pemphigus has several parts:
- A visual examination by a dermatologist. The doctor will take a complete history and physical exam, noting the appearance and location of the blisters.
- A blister biopsy. A sample of a blister is removed and examined under the microscope. The doctor will look for cell separation that is characteristic of pemphigus, and will also determine the layer of skin in which the cells are separated.
- Direct immunofluorescence. A biopsy of a skin sample is treated in the laboratory with a chemical compound to find the abnormal desmoglein antibodies that attack the skin. The specific type of antibodies that form may indicate what type of pemphigus exists.
- Indirect immunofluorescence. Sometimes called an antibody titre test, a sample of blood is tested to measure pemphigus antibody levels in the blood and to help determine the severity of the disease. Once treatment begins, this blood test may also be used to find out if treatment is working.
Pemphigus is a serious disease, and it is important to do all of these tests to confirm a diagnosis. No single test is right all of the time.
Because it is rare, pemphigus is often the last disease considered during diagnosis. Early diagnosis may permit successful treatment with only low levels of medication, so consult a doctor if you have persistent blisters on the skin or in the mouth. In the most common form of pemphigus (pemphigus vulgaris), the mouth is often the first place that blisters or sores appear.
Pemphigus is a rare disease of the skin; therefore, dermatologists are the doctors best equipped to diagnose and treat people with pemphigus. If you have blisters in the mouth, a dentist can provide guidance for maintaining good oral health. This is important for preventing gum disease and tooth loss.
Treatment for pemphigus vulgaris involves using one or more drugs. High-dose oral corticosteroids, such as prednisone or prednisolone, are the main treatment for pemphigus. These are anti-inflammatory medicines that suppress the immune system. High doses are often required to bring pemphigus under control. To minimize the side effects patients may experience, once the disease begins to subside the corticosteroid levels are reduced slowly to the lowest level required to prevent new blisters or sores from appearing. Many patients will go into complete remission with treatment, although this may take a number of years. Other patients will need to continue to take small doses of medication to keep the disease under control. Prednisone is usually taken by mouth, but can also be injected into a vein, muscle, or directly into a blister. The route depends on the type and severity of disease. Usually, a corticosteroid cream will be used directly on the blisters.
To keep the levels of corticosteroid use to a minimum, immunosuppressive drugs are often added to a patient’s treatment. These are drugs that stop or slow down the immune system’s response to what it sees as an attack on the body. They include:
- Myco-phenolate mofetil
Other drugs that may be used include:
- Diamino-diphenyl sulfone
- Antibiotics such as tetracycline.
All of these medications can cause serious side effects. You should see your doctor regularly for blood and urine tests. Be sure to report any problems or side effects you experience to the doctor. With prolonged high-dose corticosteroid therapy, common side effects include susceptibility to life-threatening infections, delayed wound healing, osteoporosis, cataracts, glaucoma, type 2 diabetes, loss of muscle mass, peptic ulcers, swelling of the face and upper back, and salt and water retention. To reduce the risk of osteoporosis, bone density measurements are taken, and patients with low bone density are prescribed medications such as alendronate or risedronate. Extra calcium and vitamin D intake, exercise, and stopping smoking are also recommended. For diabetes caused by steroid use, patients must be on a low sugar diet and may need to take antidiabetic medications.
The immunosuppressive drugs that are used to treat pemphigus can also increase the chances of developing an infection and may cause anemia (a decrease in the white blood cells in the blood) inflammation of the liver, nausea, vomiting, or allergic reactions.
People with severe pemphigus that cannot be controlled with corticosteroids may undergo plasmapheresis, a treatment in which the blood containing the damaging antibodies is removed and replaced with blood that is free of antibodies. Such patients can also be treated with IVIg, or intravenous immunoglobulin, which is given daily for 3 to 5 days, every 2 to 4 weeks for 1 to several months. Plasmapheresis and IVIg are both very expensive treatments, since they require large amounts of donated and specially processed blood. Scientists have reported success in treating difficult cases of pemphigus vulgaris with a combination of IVIg and rituximab, a cancer medication.
The treatment prescribed will depend on the type of pemphigus and the severity of the disease. Work closely with your doctor to devise the treatment regimen that works best for you. Because the medications used to treat pemphigus are strong medications with potentially serious side effects, every doctor that you see should be made aware of the type and amount of medications you are taking.
It may take several months to years for the ulcers and blisters of pemphigus vulgaris to disappear after treatment has begun because circulating antibodies remain in the blood for a long time. Lesions in the mouth are particularly slow to heal. Blisters in the mouth can make brushing the teeth painful, leaving you prone to gum disease and tooth loss. A dentist can offer approaches that enable you to maintain healthy teeth and gums. Avoiding spicy, hard, and acidic foods will help, since those foods can irritate or trigger the blisters. If you are taking corticosteroids, you should receive advice for maintaining a diet low in calories, fat, and sodium, and high in potassium and calcium.
The outlook for people with pemphigus has changed dramatically in the past 40 years. A person diagnosed with pemphigus vulgaris in the 1960s faced the reality that they had a disease that was rare, usually fatal, poorly understood, and with no good treatment options. Today, through medical research supported by the National Institutes of Health (NIH), the picture is dramatically better. The disease is now rarely fatal, and the majority of deaths occur from infections. For most people with pemphigus, the disease can be controlled with corticosteroids and other medications, and these medications can eventually be completely discontinued. However, as described earlier, these medications can cause side effects that may sometimes be serious. Pemphigus and its treatments can be debilitating and cause lost time at work, weight loss, loss of sleep, and emotional distress. The International Pemphigus Foundation provides patient support services to help people with the disease cope with its effects.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health, supports a broad range of research on pemphigus to better understand what causes various forms of the disease and to develop better treatments. When researchers began to understand that pemphigus is an autoimmune disease, they were able to target their laboratory studies on immune function and to apply research advances in other autoimmune diseases to pemphigus. They have already clarified that effective therapies against this disease must stop production of the antibodies that attack the skin cells.
Environmental and genetic risk factors. Researchers are trying to determine the environmental and genetic risk factors for pemphigus by studying populations that have high rates of the disease, such as people living in certain rural areas of Brazil.
Basic research. Scientists are conducting laboratory studies of antibodies that attack skin cells to determine how different antibodies contribute to this disease. They are also studying the genes involved when the body’s antibodies attack healthy tissue.
Other NIAMS-supported researchers are studying animal models of various forms of pemphigus to define the events that trigger the development of the blistering skin and mucous membranes.
- Investigators have found that a certain protein, called p38 mitogen-activated protein kinase (p38 MAPK), is activated in mice with pemphigus, and that blocking this protein prevents blisters. This may lead to a way to prevent a specific immune response without having to suppress the entire immune system.
- Desmoglein is the target of antibodies in pemphigus. Researchers are looking at how desmoglein functions as a cell adhesive and how pemphigus disrupts that function. Desmoglein also appears to have a role beyond that of cellular adhesion, and researchers are studying its role in forming skin cells.
Designing better treatment options. Other scientists are devising treatments to avoid the use of high-dose corticosteroids altogether. They are working to design drugs that more effectively inhibit antibody formation without the side effects that can occur with current treatments.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health
American Academy of Dermatology (AAD)
The International Pemphigus & Pemphigoid Foundation
American Autoimmune-Related Diseases Association, Inc. (AARDA)
National Organization For Rare Disorders (NORD)
Adverse reaction. An unwanted effect attributed to a medication or therapy.
Animal model. A laboratory animal useful for medical research because it has specific characteristics that resemble a human disease or disorder. Scientists can create animal models, often laboratory mice, by transferring altered genes into them.
Antibodies. Proteins made by the body to attack foreign invaders, such as viruses and harmful bacteria, to keep the body healthy.
Autoantibodies. Antibodies that attack one’s own cells.
Autoimmunity. Immune responses that are inappropriately directed at a person’s own tissues.
Cataracts. Clouding of the lens of the eye.
Corticosteroids. Potent anti-inflammatory hormones that are made naturally in the body or synthetically (man-made) for use as drugs. They are also called glucocorticoids. The most commonly prescribed drug of this type is prednisone. Dapsone: An anti-inflammatory drug that was first used to treat leprosy.
Dermatologist. A doctor who treats problems of the skin, hair, and nails.
Dermis. The layer of skin cells under the uppermost layer, the epidermis.
Desmogleins. Proteins in the cells of the skin that form the “glue” that connects adjacent skin cells, keeping the skin intact.
Epidermis. The uppermost layer of skin cells.
Gene. The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
Genetic predisposition. A state in which genetic makeup leaves an individual more susceptible to disease.
Glaucoma. Abnormally high fluid pressure in the eye that can lead to vision loss or blindness.
Immune system. A complex network of specialized cells and organs that work together to defend the body against attacks by “foreign” invaders such as bacteria and viruses. In some conditions, it appears that the immune system does not function properly and may even work against the body.
Immunofluorescence. A specific type of laboratory test on a tissue or blood sample that is used to detect antibodies that can attack skin. The specific antibodies are labeled with a compound that makes them glow when observed microscopically under ultraviolet light.
Immunosuppressive drugs. Drugs that suppress the immune response and can be used to treat autoimmune disease. Unfortunately, because normal immunity is also suppressed with these drugs, they leave the body at risk for infection.
Infection. Invasion of body tissues by bacteria or other tiny invaders that cause illness.
Osteoporosis. A disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased risk of fractures.
NIAMS gratefully acknowledges the assistance of the following individuals in the preparation and review of previous versions of this booklet: Carl Baker, M.D., and Alan Moshell, M.D., NIAMS; Jean Bystryn, M.D., New York University School of Medicine; Luis Diaz, M.D., the University of North Carolina, Chapel Hill; and John Stanley, M.D., the University of Pennsylvania School of Medicine.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. Additional information can be found on the NIAMS Web site at www.niams.nih.gov.
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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NIH Publication No. 07–7083