Pemphigus vulgaris

Definitions & Key takeaways

Pemphigus Vulgaris is an autoimmune skin condition caused by antibodies that attack the epithelial cells in the skin and mucous membranes and form blisters. Symptoms include mucus membrane and skin blisters, and fever. Treatment usually involves corticosteroids and other immunosuppressive medications to suppress the immune system and reduce inflammation.

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Introduction0:00–0:13

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.

Skin0:13–2:18

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, than 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.

Pathophysiology2:18–4:30

Pemphigus vulgaris is a type II hypersensitivity reaction, which is when the immune system produces antibodies that bind to the body's own cells.
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.
In that process, proteases get released, which are enzymes that break down the proteins that make up the desmosomes. The loss of desmosomes leads to acantholysis, which is the process of cells letting go of one another, and that directly leads to the formation of bullae, or blisters.
Since hemidesmosomes are not affected, basal cells remain anchored to the basement membrane, but separate from other cells of the epidermis - and that’s called tombstoning.
So the bullae of pemphigus vulgaris are intraepidermal, meaning that they’re within the epidermis, while the bullae of a similar disease, bullous pemphigoid are subepidermal, between epidermis and dermis.

Symptoms4:30–5:14

Early on in pemphigus vulgaris there can be bullae and ulcerations on the oral mucosa, but any type of mucosa can be affected.
The oral lesions can be very painful and can lead a person to have difficulty with eating and drinking. The mucocutaneous form develops skin lesions as well.
At first, the affected skin has flat red areas called macules, and they can appear almost anywhere on the body. Over time the macules develop into bullae or blisters, which eventually rupture and leave painful erosions.
Sometimes, the lesions can get infected and that can worsen the pain and discomfort. A classic sign to help diagnose pemphigus vulgaris is the Nikolsky’s sign - which is when lateral pressure is applied to the lesion, and it causes a split to form between the upper and lower layers of the epidermis.

Diagnosis5:14–5:55

In other skin conditions, like bullous pemphigoid, the skin doesn’t split, resulting in a negative Nikolsky’s sign. In addition, a skin biopsy can be used to look for signs of acantholysis and tombstoning.
Finally, direct immunofluorescence can be used. That’s where antibodies marked with fluorescent molecules, are used to tag the autoreactive IgG antibodies, which are attacking the epidermal cells.

Treatment5:55–6:25

Treatment of pemphigus vulgaris can include both topical and systemic corticosteroids depending on the severity of the disease.
In addition, rituximab can be used. Rituximab is a monoclonal antibody, which binds to B cells and inhibits the production of anti desmosomal IgG antibodies.
Finally, to lessen the pain of the oral lesions, topical rinses like viscous lidocaine can be used. All right, as a quick recap pemphigus vulgaris is an autoimmune skin disorder where B cells create IgG antibodies that target desmoglein 1 and 3.

Review6:25–7:01

The destruction of these desmosome proteins leads to the formation of intraepidermal blisters in the mucosa and the skin.
Symptoms include oral and skin lesions and flaccid blisters, which can be diagnosed by a positive Nikolsky’s sign, skin biopsy, or direct immunofluorescence.
Topical and systemic corticosteroids, and rituximab can be used to treat the disease.