Hidradenitis Suppurativa cause, genetics and treatment [Beta]


Uploaded by slentzen on 16.08.2012

Transcript:
This is very early work for the first of three videos to be produced. The hand drawn sketches
are just illustrations, and the final video will be animated by a professional.
Below is a transcript of the narration:
Hidradenitis Suppurativa also known as Acne Inversa, is a genetic skin disorder affecting
around 3% of the population.
It is characterized by recurrent boil-like lumps or abscesses forming under the skin.
They are most often found in the armpits, the chest
The disorder is characterized by recurrent boil-like lumps or abscesses forming under
the skin. The lumps are often found in the armpits, chest, groin, buttocks and the neck
When the disorder is more severe, the lumps are also seen forming in order areas of the
body
To explain what an abscess is, and how it can be recognized, we will take a closer look
at the skin
Here a cross section of the skin is shown. The outer most layer of the skin consists
of dead skin cells and is called the Stratum Corneum.
Below the Stratum Corneum, living skin-cells in the epidermis are multiplying and forming
the new skin layers. The deepest layer in the skin is called the dermis; the dermis
contains the sweat glands, hair cells, nerves and immune cells.
In people with Hidradenitis Suppurativa an abscess is created when an area of the skin
becomes inflammated. Inflammation is the body’s own reaction to a foreign object such as an
infection, or in the case of HS it is caused by a malfunctioning of the immune system.
Inflammation is thus the reaction to an infection, and not the infection itself
The very same inflammation caused by the immune system, used to protect the skin, can in some
cases also cause tissue damage in the skin, thus killing the skin-cells
As the inflammation expands, skin cells will start to die and bacteria living naturally
on the skin will start to feed on the leftovers. Finally, as a last resort to stop the spreading
of the inflammation, the surrounding skin cells will change and create scar tissue around
the area of the inflammation. This creates a wall of scar tissue with a pus filled core,
and this is what is called an abscess
The abscess will feel like a lump similar to a ping pong ball or a golf ball beneath
the skin, it will be extremely sensitive and painful to touch. In some cases a small hole
will eventually form allowing the pus filled core to be drained, but in the more severe
cases of HS several abscesses located next to each other can start growing together into
intricate networks. The size and shape of the abscess may vary, sometimes looking like
a big pimple or zit, and other times a small red nodules, but they all come from the same
genetic cause in the affected person.
To understand the mechanisms behind HS, we must take a closer look at how the skin and
the immune system protects us from the numerous microorganisms that reside on the healthy
normal skin of every person, and what will happen when this system designed to protect
us, fails
There are numerous microorganisms that live on the surface of the skin; there they feed
on the dead skin cells being shed from the body. As they move around, some of the microorganisms
may move down along the space between the skin and hairs sticking out of the skin.
Once inside the skin, the microorganism will start to multiply
Initially the microorganisms will multiply without any difficulties as the skin cells
are not able to attack it.
Eventually, there will be so many microorganisms that they have started to pose a problem to
the skin cells, and as a result the skin cells will send out small signalling molecules.
The purpose of these signalling molecules known as cytokines is to alert nearby cells
from the immune system, and help them migrate towards the area so they can kill the intruders
The small signalling molecules, also known as cytokines acts as a scent that nearby cells
of the immune system will sniff out, and soon the first line of defence against microbes
will arrive. There are numerous types of immune cells in the body, each one doing a particular
task, but some of the first ones to arrive at the area of infection in the skin will
be macrophages and neutrophils. For simplicity we will only show the macrophages.
When the macrophages arrive at the scene of infection, the signalling molecules that helped
them find their way, will also make them become aggressive towards any threats to the skin
cells. The Macrophages have an ability to recognize any microorganism that is not part
of the body and will start eating up the microorganisms it finds.
Once the macrophages start engulfing and eating the surrounding bacteria, and thus killing
them, they too start releasing small signalling molecules such as cytokines. In fact they
release some of the same cytokines like the skin cells did in the first place. These cytokines
released by both macrophages and skin cells will also stimulate the skin cells to release
even more of the very same cytokines.
As the concentration of cytokines increases, other immune cells will arrive and do their
part in the fight against the primary infection.
As many of the cytokines released amplifies their own release, a positive feedback loop
is created. This is similar to playing the sound from a speaker back into the microphone,
creating the amplification and distortion sometimes heard at a concert. To avoid this
self-amplification problem, the immune system has developed a number of different ways to
regulate the signalling and avoid too much signalling being generated.
For yet unknown reasons, the mechanisms that are supposed to keep all these signals in
balance fails, and too much of the signalling molecules named tumor necrosis factor alpha,
inter leukin 1 beta, inter leukin 6 and many more are released in too large an amount.
Studies have shown that HS patients have up to 30 times higher concentration of these
molecules in their skin than normal people.
This massive release of cytokines causes the immune cells to be over activated, and instead
of protecting the skin cells, by killing the bacterias, they start going on a killing frenzy,
and kills everything around them.
As the immune cells start killing more skin cells, the skin cells will send out more cytokines
to alert more immune cells from further away that they are being attacked and that they
need the immune cells to come and protect them
Now even more immune cells will migrate towards the area. As HS is a genetic disease, all
the cells in the body will have the same systemic error, and this misregulation will start amplifying
itself. In the end massive death of skin cells will trigger the last line of defence known
by the body for when everything else fails.
It is now clear to the skin cells that something is seriously wrong, and they will start to
form scar tissue around the infected site in order to create an impenetrable barrier
for the growing abscess. Immune cells and bacteria are in the core of the battle, and
thus the abscess is born