Bullous Pemphigoid

What happens in bullous pemphigoid

Skin has an outer layer (epidermis) attached to a deeper layer (dermis) by a sheet of anchoring proteins called the basement membrane. In bullous pemphigoid, the immune system makes antibodies against two of these proteins, known as BP180 and BP230. The antibodies trigger inflammation that dissolves the anchors, and fluid fills the gap.

Because the split is deep, below the entire epidermis, the blister roof is thick. That is why pemphigoid blisters are tense and stay intact for days, unlike the fragile, quickly bursting blisters of pemphigus.

Symptoms

Early stage (non-bullous phase)

For weeks or months before any blisters, many people have only:

• intense itching, often worse at night
• red, raised patches that look like hives or eczema

At this stage it is often mistaken for eczema, hives or dry-skin itch. Some people never progress to blisters.

Blistering stage

• Tense blisters 1 to 3 cm (0.5 to 1 in) or larger, filled with clear or sometimes bloodstained fluid
• Blisters on red or normal-looking skin
• Common sites: inner thighs, groin, armpits, flexural creases of the arms and legs, and the lower belly
• Raw areas and crusts where blisters burst, which heal without scarring
• Mouth blisters in about 1 in 10 to 1 in 5 people, usually mild

Causes and triggers

Bullous pemphigoid is autoimmune, and the reason the immune system starts targeting skin proteins is not fully known. Recognized links include:

• Age: risk rises steeply after 70, likely from age-related immune changes.
• Medicines: DPP-4 inhibitors (gliptins) for type 2 diabetes, such as sitagliptin, linagliptin and vildagliptin, are the best-known trigger. Others include some diuretics such as furosemide and spironolactone, certain antibiotics, and immune checkpoint inhibitors for cancer.
• Neurological disease: people with dementia, Parkinson's disease, stroke or multiple sclerosis are 2 to 5 times more likely to develop it.
• Other triggers: ultraviolet light, radiotherapy, burns and skin trauma occasionally set off the first flare.

Bullous pemphigoid vs pemphigus and other blistering diseases

When blistering mainly affects the mouth, eyes and genitals and leaves scars, the diagnosis is usually mucous membrane pemphigoid, a related but more scarring disease.

How it is diagnosed

1. Examination of the blisters, itch and distribution.
2. Skin biopsy: one sample from the edge of a fresh blister for routine microscopy, which shows a split below the epidermis with eosinophils (a type of white blood cell).
3. Direct immunofluorescence: a second biopsy from normal-looking skin next to a blister. A line of antibody and complement along the basement membrane confirms pemphigoid.
4. Blood tests: BP180 and BP230 antibody levels. BP180 levels often track disease activity.
5. Medicine review: especially gliptins started in the past months or years.

Treatment

The aims are to stop new blisters, control itch and avoid steroid side effects in older people.

• Very potent topical steroids: clobetasol cream applied to the whole body (except the face) is as effective as steroid tablets for widespread disease and causes fewer side effects. It is tapered slowly over months.
• Steroid tablets: prednisolone or prednisone for extensive disease, at the lowest effective dose. Bone protection, blood-sugar and blood-pressure checks are needed.
• Doxycycline: an antibiotic with anti-inflammatory effects. It works more slowly than steroids but is safer for long-term use in mild to moderate disease.
• Steroid-sparing drugs: methotrexate, azathioprine, mycophenolate or dapsone.
• Biologics: dupilumab, which blocks a key itch and allergy pathway, is now approved in the US for bullous pemphigoid. Rituximab and omalizumab are used for resistant cases.
• Stopping a trigger medicine: if a gliptin is suspected, it is usually stopped in discussion with the diabetes team.

Blister and skin care

• Large blisters can be pierced at the base with a sterile needle to drain fluid while leaving the roof in place as a natural dressing. A nurse can show you how.
• Cover raw areas with non-stick dressings.
• Use plenty of fragrance-free emollient to ease itch.
• Watch for infection: increasing pain, pus, yellow crusts or spreading redness.

Complications

• Skin infection and, rarely, sepsis
• Side effects of long-term steroids: diabetes, bone thinning, infections, muscle weakness
• Reduced mobility and sleep from itch

Outlook

Bullous pemphigoid usually burns out on its own. Most people can stop treatment within 1 to 5 years, though roughly a third relapse, usually in the first year after stopping. It is a more serious disease than its skin signs suggest because it affects frail older adults: overall death rates in the first year are higher than in people of the same age without it, mainly because of underlying illness and treatment side effects. Careful, lower-dose treatment has improved this.

Frequently asked questions

What does bullous pemphigoid look like at first?

Often it does not look like a blistering disease at all. The first signs are usually severe itching and red, raised, hive-like or eczema-like patches on the limbs and trunk. Tense blisters typically appear weeks to months later, often on the inner thighs, armpits and lower belly.

What is the difference between pemphigoid and pemphigus?

Both are autoimmune blistering diseases. In pemphigoid the split is below the epidermis, so blisters are tense and stay intact, the mouth is rarely involved and it affects older adults. In pemphigus the split is within the epidermis, so blisters burst easily, mouth sores are common and it is usually more serious.

Is bullous pemphigoid contagious?

No. It is caused by the person's own immune system, not by an infection. It cannot be spread by touching blisters, sharing towels or living together. Burst blisters can become infected with ordinary skin bacteria, so they still need clean care.

Can medications cause bullous pemphigoid?

Yes. Gliptins (DPP-4 inhibitors) used for type 2 diabetes are the best-known trigger. Some diuretics, antibiotics and cancer immunotherapy drugs are also linked. Stopping the medicine helps some people but does not always clear the disease, so standard treatment is usually still needed.

What is the life expectancy with bullous pemphigoid?

The disease itself is rarely fatal, and many people live for many years with it in remission. Because most patients are elderly with other illnesses, and steroids have side effects, the risk of death in the first year is higher than average. Prompt diagnosis and gentle, targeted treatment lower that risk.