Almost everyone gets a blister or two every once in a while. But if your blisters do not heal, or if they multiply, it could indicate a rare, serious disease called pemphigus.
Pemphigus is an autoimmune condition that affects the skin and mucous membranes (the moist inner lining of your mouth, nose and genitals), resulting in blisters, sores, or small bumps that fill with pus or fluid. The disease is caused by the immune system being misdirected.
“In pemphigus, the immune system has targeted a certain family of proteins that hold your skin cells together. Once the immune system goes after those proteins, the skin cells fall apart from one another and you get blisters,” says Donna Culton, MD, PhD, associate professor of dermatology at UNC Health Care.
UNC Medical Center dermatologists treat about 80 patients a year from across the state and neighboring states who are diagnosed with pemphigus. Certain populations, such as Ashkenazi Jews, are more frequently affected by the disease; however, pemphigus can affect anyone regardless of race or ethnicity.
Typically, the disease occurs in adults ages 40 to 60 years old. But there are exceptions; at UNC, a patient as young as 8 years old was treated.
Types of Pemphigus and Symptoms
There are two major types of pemphigus:
- Pemphigus vulgaris is the most common form and usually begins with blisters in the mouth. Blisters also typically form on the skin or genital mucous membranes. Patients feel a burning, sharp or stabbing pain with the blisters.
- Pemphigus foliaceus causes blisters only on the skin of the back and chest (not the mouth or other mucosal tissues).
Two other types of pemphigus are extremely rare:
- IgA pemphigus is usually limited to the skin and mainly involves small bumps filled with pus.
- Paraneoplastic pemphigus is very severe and is associated with certain forms of cancer. It often affects the lungs in some patients.
Diagnosing Pemphigus
Pemphigus can present in a variety of places, including the nose and genitals, but blisters are predominately seen in the mouth for most patients. It is often misdiagnosed, and it can take years and seeing multiple physicians to get an accurate diagnosis.
“Patients will go to the dentist, who may not recognize it as something as severe as it is and may think it’s irritation from brushing. And that same patient may have blisters in their genital mucosa and may not be putting it together. Since it is presented in so many places, it takes a long time to get it diagnosed for a lot of patients,” Dr. Culton says.
Becky Strong, outreach director for the International Pemphigus and Pemphigoid Foundation, was diagnosed with pemphigus vulgaris in 2010 after 17 months of multiple missed diagnoses.
“I went to my dentist for my six-month cleaning and I told her about all of my symptoms, and she told me I had bad oral hygiene and that I needed to brush more,” Strong says.
“It’s assumed that it’s not as bad as it really is. It’s a hard journey to get a diagnosis. You’re fighting your own mind. You’re fighting your body. Sometimes you’re fighting the medical system, which makes it very hard to be treated properly.”
A biopsy is necessary to make a diagnosis of pemphigus. However, a biopsy can be tricky depending on the location of the blister. Certain places in the mouth or other mucosa tissues can be challenging for a biopsy, which can lead to a delay in a diagnosis. It’s easier to biopsy lesions on the skin.
According to the National Center for Biotechnology Information, there are 32 cases of pemphigus per million in the Jewish population in the United States. Estimates for the broader population are difficult to pinpoint. Because pemphigus is so rare, it is often the last disease considered by doctors. But early diagnosis is beneficial, because it may permit successful treatment with only low levels of medication. Dr. Culton urges patients to advocate for themselves and ask for a biopsy, especially if they have experienced sores for more than a month.
People concerned about pemphigus should ask themselves the following questions and share the answers with their doctor.
- Is this the first time having lesions?
- Do you have more than one blister in your mouth?
- Do you have a blister or lesion that’s lasted longer than a week?
- Have you continually had blisters or lesions that don’t heal?
- Do you have blisters or lesions located outside your mouth?
Treatments for Pemphigus
Pemphigus is a potentially life-threatening disease. Prior to any effective treatments, patients could die due to open sores, which could lead to severe infections. Now with treatments available, there are fewer deaths, but the treatments themselves can suppress the immune system and lead to life-threatening infections.
For Strong, the disease has been in remission since September 2013. She took several medications to get her symptoms under control.
“I’ll never forget the day when I woke up for the first time and had no new lesions, and it was probably six months later when all of my lesions had cleared up,” Strong says.
Rituximab, the first medication approved by the FDA in 2018 to treat pemphigus, has significantly helped improve symptoms of the disease and has been shown in studies to be most effective.
Other common medications available to treat pemphigus include prednisone, azathioprine and mycophenolate.
“At UNC, we offer comprehensive care that focuses on accurate diagnosis and treatment of this disease in an experienced and caring environment. We also offer patients the option to participate in clinical trials that test the newest treatments available,” Dr. Culton says.
Clinical Trials for Pemphigus
UNC Health Care is hosting the PEGASUS Clinical Trial to test a new oral medication. The study, sponsored by Principia Biopharma, Inc., is in phase three and is actively enrolling and recruiting patients.
This new medication will be used to target B cells, the critical cells that become erratic in the disease. Researchers hope to determine if the medication will work on patients’ immune systems to block the autoimmune process that eventually leads to pemphigus vulgaris and pemphigus foliaceus. For more information on this study, please contact the UNC Dermatology Clinical Trials Unit at (984) 974-3682.
“As with many rare diseases, there have been no new treatments for pemphigus for years due to lack of research. However, now finally pemphigus is having ‘a moment’—this is a very exciting time for patients,” Dr. Culton says.
If you think you may have pemphigus or a possible autoimmune skin condition, talk to your doctor. If you need a doctor, find one near you.