Bullous pemphigoid

by Katelynn Campbell MD and Allison Osmond MD FRCPC
November 14, 2024

Bullous pemphigoid is an autoimmune disease that causes fluid-filled blisters. The blisters commonly occur on the skin but can also develop inside the mouth and on the eye. An autoimmune disease is a condition that develops when the immune system inappropriately damages normal, healthy tissue in the body. The damage can be caused directly by immune cells or specialized proteins called antibodies made by immune cells.

What causes bullous pemphigoid?

The skin comprises three layers: epidermis, dermis, and subcutaneous fat. The epidermis is the surface and the part you can see when you look at your skin. Below the epidermis is a layer of connective tissue called the dermis. The epidermis is connected to the dermis by a thin layer of tissue called the basement membrane.

Most of the cells in the epidermis are called squamous cells. These cells are held together using a specialized protein called a desmosome. Another specialized protein called a hemidesmosome attaches the squamous cells to the basement membrane. The skin’s strength and health depend on whether the desmosomes and hemidesmosomes function normally.

Bullous pemphigoid is caused by antibodies that stick to the hemidesmosomes at the bottom of the epidermis. When covered with antibodies, the hemidesmosomes cannot function normally, and the epidermis separates from the basement membrane. As a result, a fluid-filled blister forms between the epidermis and the dermis.

How is this diagnosis made?

If your doctor suspects you have a blistering disease such as bullous pemphigoid, they should remove two small tissue samples in a biopsy. The first sample should be placed in formalin so it can be examined by a pathologist using a light microscope. The second sample should be placed in a special preservative that allows the tissue to be examined under an immunofluorescent microscope.

Microscopic features

When the tissue sample is examined using a light microscope, bullous pemphigoid will show a fluid-filled space separating the epidermis from the dermis below. This space is often described as a blister. Inflammatory cells may also be seen in the fluid or the surrounding tissue.

Immunofluorescence

Immunofluorescence is a test that allows pathologists to see where different types of proteins are in a tissue sample. For bullous pemphigoid, this test can be used to look for antibodies and to see where those antibodies are in the tissue.

To diagnose bullous pemphigoid, your pathologist should see antibodies stuck to the squamous cells at the bottom of the epidermis. If antibodies are found but are not stuck to the squamous cells at the bottom of the epidermis, another diagnosis should be considered.