Pemphigoid is a rare blistering disorder that primarily affects older adults, causing large, fluid-filled blisters on the skin and sometimes inside the mouth. Though the condition can be uncomfortable and persistent, it often responds well to treatment and may eventually resolve on its own over time.

What Is Pemphigoid?

Pemphigoid is a group of rare conditions where the body’s immune system mistakenly attacks healthy skin tissue. The most common form is called bullous pemphigoid, which is a term used to describe large, fluid-filled blisters that appear on the skin. Unlike some other blistering conditions, these blisters are typically firm and tense, meaning they don’t break open easily. When they do eventually burst, they usually heal without leaving permanent scars, though some skin color changes may remain after the inflammation settles down.^[1][2]

This is not a contagious condition. You cannot catch pemphigoid from another person, and it is not caused by poor hygiene, diet, or lifestyle choices. It is also not hereditary, so it cannot be passed on to your children. The condition belongs to a family of autoimmune disorders where the immune system, which normally protects the body from infections, begins attacking its own tissues instead.^[5][7]

How Common Is Pemphigoid?

Pemphigoid is considered quite rare in the general population. In the United States, there are between 6 and 13 new cases diagnosed per million people each year. In Central Europe, the numbers are similar, ranging from 12 to 13 cases per million annually. The condition affects men and women equally and does not show a preference for any particular race or ethnicity.^[4]

The condition is most commonly seen in people over the age of 60, and it becomes increasingly common with advancing age. In fact, among people who are 80 years old or older, the incidence rises dramatically to between 190 and 312 cases per million. While pemphigoid can technically occur in younger adults, and even rarely in children, the vast majority of patients are elderly.^[4][6]

Bullous pemphigoid represents about 80 percent of all cases of subepidermal blistering diseases, making it the most common type within this category of conditions. Despite being the most frequent form, it remains a rare disorder overall.^[3][4]

What Causes Pemphigoid?

Pemphigoid is an autoimmune disease, which means it occurs when the immune system malfunctions and begins to attack healthy parts of the body. In this case, the immune system produces proteins called antibodies that target and damage the layer of tissue connecting the outer skin to the deeper layers beneath. This attack weakens the connections between skin layers, causing them to separate and fill with fluid, forming blisters.^[1][2]

More specifically, the antibodies in pemphigoid target two important proteins called BP180 and BP230. These proteins are part of structures called hemidesmosomes, which act like anchors holding the top layer of skin firmly attached to the layer underneath. When antibodies attack these proteins, the anchors are destroyed, and the skin layers separate, creating space where fluid accumulates and forms a blister.^[6][13]

Healthcare providers and researchers are still working to understand exactly why the immune system turns against the body in this way. However, certain triggers have been identified that can set off the condition in some people. Events such as sunburn, injury to the skin, burns, or surgery have all been reported to precede the development of pemphigoid. In some cases, the condition appears spontaneously without any obvious trigger.^[2][5]

Certain medications have been linked to triggering pemphigoid. The drugs most commonly associated with the condition include PD-1 inhibitor immunotherapies such as pembrolizumab and nivolumab, which are used to treat cancers like melanoma. These medications can cause pemphigoid in about 0.3 percent of cancer patients who receive them, sometimes appearing even after the treatment has been discontinued. Another group of medications strongly linked to pemphigoid are dipeptidyl peptidase-4 inhibitors, commonly known as gliptins, which are used to treat diabetes. These include drugs like vildagliptin, sitagliptin, saxagliptin, and linagliptin. Pemphigoid typically develops about 11 months after starting these medications.^[4][6][13]

Other medications that have occasionally been reported to cause pemphigoid include certain antibiotics, diuretics like furosemide and spironolactone, non-steroidal anti-inflammatory drugs, captopril, penicillamine, gold, sulfasalazine, and some antipsychotic medications.^[4][6]

Who Is at Risk?

Age is the most significant risk factor for developing pemphigoid. The condition predominantly affects people over 60 years old, with the highest rates occurring in those over 80. While younger people can develop the condition, it is uncommon in adults under 50 and rare in children.^[1][6]

People with certain neurological conditions appear to be at higher risk of developing pemphigoid. These conditions include stroke, dementia, Parkinson’s disease, epilepsy, and multiple sclerosis. Researchers believe there may be a connection because the proteins targeted by antibodies in pemphigoid are also found in the central nervous system, not just in the skin.^[6][11][13]

Individuals with psoriasis also have a greater risk of developing bullous pemphigoid, and in some cases, treatment of psoriasis with phototherapy can trigger the onset of the blistering condition. There may also be an association between pemphigoid and internal malignancy in some patients, though this connection is not fully understood.^[6][13]

Genetic factors may play a role as well. Some people carry specific variations in genes related to the immune system, called human leukocyte antigen types, which may make them more susceptible to developing pemphigoid when exposed to certain triggers throughout their lives.^[4][6]

Recognizing the Symptoms

The symptoms of pemphigoid can vary considerably from person to person, but the hallmark feature is the development of blisters on the skin. Before blisters appear, many people experience an itchy rash that may be present for several weeks or even months. This early rash can look like eczema or resemble the red, raised welts seen with hives or nettle rash. The itching can be very severe and bothersome, sometimes starting long before any blisters form.^[1][2][5]

When blisters do develop, they are typically large and firm, measuring anywhere from one to four centimeters in diameter. The blisters are described as tense, meaning they are filled tightly with fluid and have a strong outer wall that doesn’t rupture easily. The fluid inside is usually clear, though in some cases it can be cloudy, yellowish, or contain blood. Because these blisters are so firm, they may remain intact for days before eventually breaking open.^[3][5][7]

The blisters can appear anywhere on the body, but they most commonly develop in areas where the skin naturally folds or flexes. Common locations include the upper thighs, armpits, the insides of elbows, hands, feet, and the abdomen. The skin around the blisters may look normal, or it may appear red, pink, dark reddish-brown, or slightly darker than the person’s usual skin color, depending on their skin tone.^[1][2][5]

When blisters break open, they leave behind raw, sore areas that can be painful. However, these areas usually heal without leaving permanent scars, though the skin may remain darker or lighter than the surrounding area for some time after the inflammation has settled. In severe cases, blisters can cover large areas of the body.^[1][2][7]

Some people with pemphigoid also develop blisters inside their mouth. This occurs in roughly one-quarter to one-third of patients. Mouth blisters can make eating and swallowing difficult and uncomfortable. When pemphigoid affects the mouth, gums, or other mucous membranes more extensively, the condition may be classified as a variant called mucous membrane pemphigoid.^[1][3][5]

Not everyone with pemphigoid develops visible blisters. In some patients, the condition presents only as a persistent, itchy rash with raised patches that resemble hives or eczema. This is sometimes called non-bullous pemphigoid and can make diagnosis more challenging.^[3]

Can Pemphigoid Be Prevented?

Because the exact triggers and underlying causes of pemphigoid are not fully understood, there are no specific measures known to prevent the condition from developing. However, being aware of potential triggers may help in some situations.^[2]

If you are taking medications that are known to be associated with pemphigoid, particularly cancer immunotherapy drugs or diabetes medications in the gliptin family, it’s important to be vigilant for the development of any new rash or blisters. Early recognition and prompt communication with your healthcare provider can allow for adjustments in treatment that may prevent the condition from worsening.^[6][13]

Avoiding skin trauma may be helpful, as injury, burns, and sunburn have been reported as potential triggers in some cases. Protecting your skin from excessive sun exposure, being cautious to avoid burns, and taking care to minimize injuries may be reasonable precautions, especially for people who are already at higher risk due to age or neurological conditions.^[2][5]

Since pemphigoid cannot be prevented entirely, the focus is on early detection and prompt treatment. If you develop unexplained blisters or a persistent, itchy rash that doesn’t go away within a few weeks, it’s important to see a healthcare provider for evaluation. Early diagnosis and treatment can help prevent complications and improve outcomes.^[1][2]

How the Body Is Affected

Understanding what happens inside the body during pemphigoid can help explain why the symptoms occur. The disease process involves both the immune system and the structural components of the skin working together in an abnormal way.^[4]

In healthy skin, the outermost layer, called the epidermis, is firmly attached to the layer beneath it, called the dermis. This attachment is maintained by specialized structures called hemidesmosomes, which contain proteins that act like molecular anchors. These anchors ensure that the skin layers stay connected and form a waterproof, protective barrier for the body.^[6][13]

In pemphigoid, the immune system produces antibodies that mistakenly recognize two key proteins in these anchors as foreign invaders. These proteins are called BP180 and BP230. When antibodies attach to these proteins, they activate other parts of the immune system, triggering an inflammatory response. White blood cells called neutrophils and eosinophils are recruited to the area, and they release powerful enzymes designed to destroy what the body perceives as a threat.^[4][6]

These enzymes break down the hemidesmosome structures, destroying the anchors that hold the skin layers together. When enough anchors are destroyed, the epidermis separates from the dermis. Fluid from the surrounding tissue seeps into the gap between the separated layers, accumulating and forming a visible blister on the surface of the skin. Because the separation happens below the epidermis rather than within it, the blisters are called subepidermal blisters.^[6][13]

The intense itching that often precedes blister formation is caused by the inflammatory process. Immune cells release chemical signals that stimulate nerve endings in the skin, creating the sensation of itching. This can occur even before visible blisters appear, which is why many patients experience severe itching for weeks or months before their diagnosis.^[2][13]

The inflammation and damage are limited to the area where the epidermis meets the dermis, which is why pemphigoid typically doesn’t cause scarring. Once the immune attack is controlled with treatment, the skin’s normal healing processes can repair the damage. The epidermis grows back over the exposed dermis, and the hemidesmosomes reform, restoring the normal skin structure. However, the inflammatory process can sometimes leave behind changes in skin pigmentation that persist for months or even years.^[5][7]

In some patients, the antibodies not only attack the skin but also target similar proteins found in mucous membranes, such as those lining the mouth, throat, and eyes. When this happens, blisters can form in these locations as well, leading to pain, difficulty swallowing, or eye problems.^[3][5]