Bullous pemphigoid

by Katelynn Campbell MD and Allison Osmond MD FRCPC
March 7, 2023

What is bullous pemphigoid?

Bullous pemphigoid is an autoimmune disease that causes fluid-filled blisters. The blisters commonly occur on the skin, but they 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 that are made by immune cells.

What causes bullous pemphigoid?

Skin is made up of three layers: epidermis, dermis, and subcutaneous fat. The surface and the part you can see when you look at your skin is called the epidermis. 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. The squamous cells in the epidermis are held together using a specialized protein called a desmosome. Another specialized protein called a hemidesmosome is used to attach the squamous cells to the basement membrane. The strength and health of the skin depend on both the desmosomes and hemidesmosomes functioning normally.

Bullous pemphigoid is caused by antibodies that stick to the hemidesmosomes at the bottom of the epidermis. When covered with antibodies, the hemidesmosomes are unable to 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 do pathologists make the diagnosis of bullous pemphigoid?

If your doctor suspects that you have a blistering disease such as bullous pemphigoid, they should remove two small samples of tissue in a procedure called a biopsy. The first sample should be placed in a preservative called 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.

What does bullous pemphigoid look like under the microscope?

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.

What is immunofluorescence and how is it used to make the diagnosis of bullous pemphigoid?

Immunofluorescence is a special 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 make the diagnosis of 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.