Auto news on Youtube Dec 31 2018

Bullous pemphigoid is an autoimmune skin disease that causes the skin to form bullae or blisters.

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.

The stratum basale also contains another group of cells called melanocytes, which secrete

melanin.

Melanin is a pigment protein, or coloring substance.

Below the epidermis is the basement membrane which is a thin layer of delicate tissue containing

collagen, laminins, and other proteins.

Basal cells are attached to the basement membrane by hemidesmosomes, a protein complex that

stems from the bottom of the basal cells.

Just like an anchor digs into the seafloor and holds a boat in place, hemidesmosomes

dig into the basement membrane and hold basal cells in place.

The exact cause of bullous pemphigoid is unclear, but it's thought that in a person with a

genetic precondition, it can be triggered by medications like furosemide, captopril,

penicillamine, non steroid anti-inflammatory drugs (or NSAIDs), and antibiotics.

Bullous pemphigoid is a type II hypersensitivity reaction, which is when the immune system

produces antibodies that bind to the body's own cells.

Immune cells called B cells produce IgG antibodies, which are Y shaped molecules with 2 regions,

an antigen binding fragment region - or Fab region, and fragment crystallizable region

or Fc region.

The Fab region of the antibody binds to pathogens which helps other immune cells destroy those

pathogens.

The antibodies can also activate a part of the immune system called the complement system,

which destroys the pathogen, or induces inflammation.

In bullous pemphigoid, the Fab region of IgG antibodies bind to proteins that make up the

hemidesmosome: one of the proteins is called bullous pemphigoid antigen 1 or BPAG1, which

is also called dystonin, and another protein is called bullous pemphigoid antigen 2 or

BPAG2, which is also called BP 180 or type 17 collagen - lots of names for the same thing.

The Fc region activates the complement system.

The process gets started when C1, the first of the complement proteins, binds the Fc region

of the antibody.

C1 then engages other members of the complement family - C2 through C9, some of which are

activated by being cleaved or chopped by an enzyme.

The cleaved fragments C3a, C4a, and C5a act as chemotactic factors, meaning they attract

certain cells, in this case the mast cells.

The mast cells degranulate and release molecules like tumor necrosis factor alpha, leukotrienes,

and cytokines.

These molecules attract inflammatory cells like neutrophils, eosinophils, macrophages,

and T cells.

These inflammatory cells then secrete proteolytic enzymes, which destroy the proteins of hemidesmosomes

- BPAG1 and BPAG2.

Now, If an anchor breaks it can no longer hold the boat in place and it floats away.

So, when the hemidesmosomes are destroyed the basal cells separate from the basement

membrane, and a split forms between the dermis and epidermis, resulting in what's called

a subepidermal bullae.

These subepidermal bullae are distinct from the epidermal bullae which form in the disease

pemphigus vulgaris.

In fact, in pemphigus vulgaris the bullae form as a results from breaking connections

between cells within the epidermis.

Now in bullous pemphigoid, the inflammation also affects the melanocytes, which produce

more melanin that gets stuck within the cells of the dermis.

Bullous pemphigoid is most commonly located on the lower abdomen, flexor side of the forearms,

and anterior or inner thighs, but can also involve other areas as well.

Unlike pemphigus vulgaris, it doesn't typically involve the oral mucosa.

Early on, there's a red and itchy rash, and over time it develops into large bullae

or blisters.

The blisters typically evolve over a few days, and leave behind crusted lesions that heal

without scarring.

A classic way to help distinguish bullous pemphigoid from other skin diseases like 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.

In bullous pemphigoid the skin doesn't split.

Pemphigus vulgaris will have the Nikolsky's sign, but bullous pemphigoid will not.

In addition, a skin biopsy can be done to look for evidence of antibodies and complement

infiltration into the skin.

Finally, the blood can be checked for auto-antibodies against BPAG1 and BPAG2.

Bullous pemphigoid is most commonly treated by stopping any medications that could be

triggering it and by using corticosteroids.

All right, as a quick recap, bullous pemphigoid is an autoimmune skin disease mediated by

type II hypersensitivity.

Autoantibodies form against BPAG1 and BPAG2, and they allow blisters to form between the

dermis and epidermis layers.

Large tense blisters on the lower abdomen, arms, and legs are the most common symptom.

There is no Nikolsky's sign, but there are circulating IgG antibodies, and it's usually

treated with corticosteroids.