Bullous pemphigoid is a chronic autoimmune skin disorder that causes large, fluid-filled blisters (known as bullae) and severe itching. To understand this condition, it is essential to first understand the structure of our skin. The skin is made of two main layers:

• The epidermis is the thin, protective outer layer.
• The dermis is the thicker layer beneath, which contains nerves, blood vessels, and collagen.

These two layers are held tightly together by a specialized area called the basement membrane zone. This zone contains specific proteins that act like powerful “rivets” or structural anchors, ensuring the skin remains intact and strong.

In bullous pemphigoid, the immune system makes a serious error. It produces autoantibodies that mistakenly identify two of these specific anchoring proteins (known as BP180 and BP230) as foreign invaders. These autoantibodies travel to the basement membrane zone and launch an inflammatory attack on these vital rivets. This attack destroys the anchors, causing the epidermis to separate from the dermis. A space is then created between these two layers, which fills with inflammatory fluid, forming the characteristic large, firm, and tense blisters of bullous pemphigoid.

It is important to differentiate bullous pemphigoid from another, rarer autoimmune blistering disease called pemphigus. In pemphigus, the immune system attacks the “glue” holding cells in the epidermis together. This results in very fragile, flaccid blisters that rupture easily. In bullous pemphigoid, because the split is deeper, the roof of the blister (the entire epidermis) is thick and strong, so the blisters are tense and do not break easily.

I often describe it to patients as your immune system confusing your skin as a foreign invader, fortunately, with proper treatment, we can calm that response and help the skin heal.

Bullous pemphigoid is caused by the production of autoantibodies that target the BP180 and BP230 proteins of the skin’s basement membrane zone. This binding of autoantibodies triggers a complex inflammatory cascade. It signals other immune cells, including eosinophils and neutrophils, to rush to the area. These cells then release enzymes and other chemicals that directly cause the tissue damage and separation that leads to blister formation.

The ultimate question of why an individual’s immune system suddenly becomes dysregulated and starts producing these harmful autoantibodies is unknown. It is believed to be a multifactorial process, resulting from a combination of a person’s genetic background and exposure to certain environmental or medical triggers.

In my experience, patients or families are often surprised when we connect it to a medication or neurological condition, they don’t always seem related at first glance.

Bullous pemphigoid is not contagious. It is not directly inherited in a simple pattern, although there is likely a genetic predisposition that makes some individuals more susceptible to developing this type of autoimmune response.

Primary Risk Factor: Age

The primary risk factor for developing bullous pemphigoid is older age. The vast majority of cases occur in people over age 60, and its incidence increases with each subsequent decade of life.

Potential Triggers

In a genetically susceptible older individual, the onset of the disease may be “triggered” by a specific event. While in many cases no specific trigger is identified, potential factors that have been associated with the development of bullous pemphigoid include:

• Certain Medications: A number of drugs have been implicated as potential triggers. These include certain diuretics (“water pills”), antibiotics, NSAIDs, and, more recently, a class of diabetes medications called DPP-4 inhibitors and a class of cancer drugs called checkpoint inhibitors.
• Physical Trauma to the Skin: The disease can sometimes be triggered by skin injury, such as radiation therapy for cancer, surgery, or even a severe sunburn.
• Association with Neurological Diseases: For reasons that are not yet understood, bullous pemphigoid is seen more frequently in individuals with pre-existing neurological conditions, such as Parkinson’s disease, dementia, multiple sclerosis, or a history of stroke (American Academy of Dermatology [AAD], n.d.).

I’ve seen cases arise weeks after surgery or new medication starts. It’s not about what’s wrong with the skin, it’s how the immune system decides to react.

The clinical presentation of bullous pemphigoid can often begin with a non-specific phase before the classic blisters appear.

The Prodromal Phase

For weeks or even months before any blisters form, a person may experience:

• Intense, widespread itching (pruritus). This can be the most prominent and distressing early symptom.
• An eczematous or hive-like (urticarial) rash, consisting of red, raised patches of skin.

The Bullous Phase

Following the prodromal phase, the characteristic blisters begin to form.

• Blisters (Bullae): These are large, firm, tense, fluid-filled blisters. The fluid inside is usually clear but can sometimes be cloudy or contain some blood. Because the roof of the blister is the full thickness of the epidermis, they do not rupture easily.
• Location: The blisters often arise on patches of red, inflamed skin or sometimes on normal-looking skin. They are most commonly found on the flexural surfaces of the body, the inner arms, armpits, inner thighs, groin, and lower abdomen.
• Erosions and Crusts: When the blisters do eventually break, they leave behind raw, shallow sores (erosions) that will then crust over and heal.
• Mouth Sores: While less common than in pemphigus, about 10-30% of people with bullous pemphigoid may develop sores or blisters inside the mouth.

Clinically, what stands out is the tightness of the blisters. They look like balloons stretched to the limit. Many patients say the itching is worse than the blisters themselves.

Diagnosis typically involves a clinical exam, skin biopsy, and blood tests to confirm the presence of autoantibodies.

• Clinical Examination: A dermatologist will suspect bullous pemphigoid in an older adult who presents with the characteristic combination of severe itching and large, tense bullae on the skin.
• Skin Biopsy and Direct Immunofluorescence (DIF): This is the gold standard for confirming the diagnosis. The process involves taking two small punch biopsies of the skin, usually under local anesthesia.
  • One sample is sent for standard histology. A pathologist will look at it under a microscope and can see the characteristic split in the skin at the junction between the epidermis and dermis.
  • The second sample, taken from skin right next to a blister, is sent for direct immunofluorescence (DIF). This special test uses fluorescent dyes to detect the presence of autoantibodies. In bullous pemphigoid, the DIF test will show a classic, linear deposit of IgG antibodies and/or a complement protein called C3 all along the basement membrane zone. This finding is diagnostic of the disease.
• Blood Tests: A blood test may also be performed to detect the circulating autoantibodies (anti-BP180 and anti-BP230) in the bloodstream. This is often done using a technique called ELISA.

A skin biopsy tells the whole story, it’s how we confirm it’s bullous pemphigoid and not another blistering condition, like pemphigus, which behaves very differently.

There is no cure for bullous pemphigoid, but it is a treatable condition. Treatment focuses on controlling the autoimmune response, reducing inflammation, and preventing new blisters.

1. Topical Corticosteroids

For patients with localized or moderate disease, high-potency topical corticosteroids are the first-line and preferred treatment. Applying a potent steroid cream or ointment, such as clobetasol propionate, directly to the affected skin is highly effective at controlling the inflammation and blistering. This approach minimizes the systemic side effects of taking steroid pills.

2. Oral Corticosteroids

For individuals with widespread, severe, or rapidly progressing disease, a course of oral corticosteroids, such as prednisone, is often necessary to quickly bring the severe inflammation under control. The dose is usually high initially and is then slowly tapered down as the disease responds to treatment.

3. Steroid-Sparing Agents

Because long-term use of oral steroids can have significant side effects (such as weight gain, high blood pressure, diabetes, and osteoporosis), a second medication is often added to the treatment regimen. These “steroid-sparing” agents help to control the disease and allow the dose of prednisone to be lowered more quickly and safely. Common options include:

• Doxycycline: An antibiotic from the tetracycline class that also has powerful anti-inflammatory properties.
• Other Immunosuppressants: For more severe cases, drugs like azathioprine, mycophenolate mofetil, or methotrexate may be used.

4. Biologic Therapies

For patients with very severe disease that does not respond to conventional therapies, newer biologic drugs may be used. These medications target specific parts of the immune system. Drugs like rituximab or dupilumab have been shown to be effective in treating refractory bullous pemphigoid (NORD, 2023).

5. Wound and Symptom Care

• Blister Care: It is generally best to leave intact blisters alone to serve as a natural dressing. If a blister is very large and painful, a doctor may drain it with a sterile needle while leaving the roof of the skin in place.
• Itch Control: Oral antihistamines can be helpful for controlling the severe itching, especially at night.
• Skin Care: Gentle cleansing and using moisturizers are important to maintain skin health.

When starting treatment, I often tell patients: the goal isn’t just to dry up existing blisters, it’s to calm the immune system and prevent new ones from forming altogether.

Bullous pemphigoid is a serious and distressing autoimmune condition that primarily affects older adults, causing intense itching and the formation of large, tense blisters. It is caused by a misguided immune attack on the very proteins that hold our skin together. While the appearance of the rash can be alarming, it is crucial to remember that the disease is not contagious and is highly treatable. A definitive diagnosis made by a dermatologist through a skin biopsy is the first step toward relief. What I always tell patients is this: even though bullous pemphigoid can look scary, it’s something we can control. With steady treatment and monitoring, your skin can recover, and you can get back to feeling like yourself again.

American Academy of Dermatology (AAD). (n.d.). Bullous pemphigoid and pemphigoid gestationis. Retrieved from https://www.aad.org/public/diseases/a-z/pemphigoid-bullous-overview

National Organization for Rare Disorders (NORD). (2023). Bullous Pemphigoid. Retrieved from https://rarediseases.org/rare-diseases/bullous-pemphigoid/

The Merck Manual Professional Version. (2023). Bullous Pemphigoid. Retrieved from https://www.merckmanuals.com/professional/dermatologic-disorders/bullous-diseases/bullous-pemphigoid