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Questions and Answers about Pemphigus
This publication 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 publication. If you have further questions after reading this publication, 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 where (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 immunoglobulin A or 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 may involve using one or more drugs. The main goal is to suppress the immune system so that it will stop attacking the tissues. Your doctor may prescribe corticosteroids and immunosuppressive drugs.1
1All medicines can have side effects. Some side effects may be more severe than others. You should review the package insert that comes with your medicine and ask your health care provider or pharmacist if you have any questions about the possible side effects.
Antibiotics may be prescribed as well. 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. Be sure to report any problems or side affects you experience to the doctor.
People with severe pemphigus that cannot be controlled with medicine 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 intravenous immunoglobulin (IV Ig). Plasmapheresis and IV Ig are both very expensive treatments, since they require large amounts of donated and specially processed blood. The treatment prescribed will depend on the type of pemphigus and the severity of the disease.
A dentist can offer approaches that help you to maintain healthy teeth and gums, because blisters in the mouth may make brushing and flossing your teeth painful. Avoiding certain foods may help minimize irritation of the blisters in the mouth.
The outlook for people with pemphigus has changed dramatically in the past decades. 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, 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. Support groups may help patients cope with the disease.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 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 corticosteroids altogether. They are working to design drugs that more effectively inhibit antibody formation without the side effects that can occur with current treatments.
More information on research is available from the following websites:
- NIH Clinical Research Trials and You was designed to help people learn more about clinical trials, why they matter, and how to participate. Visitors to the website will find information about the basics of participating in a clinical trial, first-hand stories from actual clinical trial volunteers, explanations from researchers, and links to how to search for a trial or enroll in a research-matching program.
- ClinicalTrials.gov offers up-to-date information for locating federally and privately supported clinical trials for a wide range of diseases and conditions.
- NIH RePORTER is an electronic tool that allows users to search a repository of both intramural and extramural NIH-funded research projects from the past 25 years and access publications (since 1985) and patents resulting from NIH funding.
- PubMed is a free service of the U.S. National Library of Medicine that lets you search millions of journal citations and abstracts in the fields of medicine, nursing, dentistry, veterinary medicine, the health care system, and preclinical sciences.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health
American Academy of Dermatology (AAD)
International Pemphigus & Pemphigoid Foundation
American Autoimmune-Related Diseases Association, Inc. (AARDA)
National Organization for Rare Disorders (NORD)
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.
Autoimmune. Literally “immunity against the self.” Autoimmune diseases occur when immune responses are inappropriately directed at a person’s own tissues.
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.
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.
The NIAMS gratefully acknowledges the assistance of the following individuals in preparation and review of the original version of this publication: Carl Baker, M.D., and Alan Moshell, M.D., NIAMS/NIH; Jean Bystryn, M.D., New York University School of Medicine, New York, NY; Luis Diaz, M.D., University of North Carolina, Chapel Hill, NC; and John Stanley, M.D., University of Pennsylvania School of Medicine, Philadelphia, PA. Cori Vanchirei was the author of this publication.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. 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 NIAMS 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 website at www.niams.nih.gov.
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Additional copies of this publication are available from:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health
NIH Publication No. 13–7083