Summary of Pemphigus vulgaris
Transcript for Pemphigus vulgaris
Content Reviewers:Rishi Desai, MD, MPH, Justin Ling, MD, MS, Evan Debevec-McKenney, Sam Gillespie, Stefan Stoisavljevic
Pemphigus vulgaris is a rare autoimmune skin disorder that causes blisters or bullae because there’s separation of skin cells.
Now, the skin is divided into three layers--the epidermis, dermis, and hypodermis.
The epidermis forms the thin outermost layer of skin.
Underneath, is the thicker dermis layer, and finally, there’s the hypodermis that anchors the skin to the underlying muscle.
The epidermis itself is made of multiple layers of developing keratinocytes - which are flat pancake-shaped cells that are named for the keratin protein that they’re filled with.
Keratinocytes start their life at the lowest layer of the epidermis called the stratum basale, or basal layer which is made of a single layer of stem cells, called basal cells that continually divide and produce new keratinocytes.
Below the epidermis is the basement membrane which is a thin layer of delicate tissue containing collagen, laminins, and other proteins.
Hemidesmosomes are a protein complex that attach basal cells to the basement membrane.
As keratinocytes in the stratum basale mature and lose the ability to divide, they migrate into the next layer, called the stratum spinosum.
The next layer up is the stratum granulosum, then stratum lucidum, and finally stratum corneum.
The cells of the epidermis are bound together by protein complexes called desmosomes, most of which are in stratum spinosum.
Similar to how the skin lines the outside of the body, mucosa lines the inside of the body, and it’s named for the surface it covers.
So there’s oral mucosa, nasal mucosa, bronchial mucosa, gastric mucosa, intestinal mucosa, and so forth.
Mucosa is made up of one or more layers of epithelial cells that sits on top of a layer of connective tissue called lamina propria.
Just like with the skin, the mucosal cells are attached to each other by protein complexes called desmosomes, and the basal cells are attached to the basal membrane by protein complexes called hemidesmosomes.
More specifically, immune cells, called B cells produce IgG antibodies that can bind to specific desmosomes proteins - desmoglein 1 and 3.
It’s unclear what triggers this to happen, but it’s thought that it happens in genetically predisposed people and gets triggered by something like a herpesvirus infection or a medication like captopril or certain antibiotics.
Now, all of the layers of the epidermis are rich in desmoglein 1 and 3, while mucosal cells predominantly have desmoglein 3.
So, in individuals with IgG antibodies that bind to both desmoglein 1 and 3, a person develops mucocutaneous pemphigus vulgaris because it affects both the skin and the mucosa.
But in individuals with IgG antibodies that only bind to desmoglein 3, a person develops mucosal pemphigus vulgaris because the mucosa is affected, but the skin isn’t really affected as there’s enough desmoglein 1 to compensate for the loss.
Now when the IgG antibodies bind to desmogleins on the surface of cells, they trigger apoptosis, or programmed cell death.