Episode 39: Epidermolysis Bullosa - A Child Like a Butterfly

Epidermolysis Bullosa: The worst disease you may have never heard of. What is it? How do we diagnose it? How do we treat it? In this episode, we’ll journey through the history of Epidermolysis Bullosa, the more common genetic causes behind the condition, and the main types of this disease. Tune in to learn more!

 

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Resources:

DEBRA US: https://www.debra.org/ 

Cure-EB (UK): https://cure-eb.org/  

EB Research Partnership Australia: https://ebresearch.org.au/ 

 

References:

https://stanmed.stanford.edu/the-butterfly-effect/

https://www.ncbi.nlm.nih.gov/books/NBK599531/ 

https://www.ncbi.nlm.nih.gov/books/NBK1369/ 

https://cure-eb.org/research/history-of-eb-research/ 

https://www.sciencedirect.com/science/article/pii/S0022202X15610557 

https://www.rch.org.au/kidsinfo/fact_sheets/epidermolysis_bullosa/ 

https://www.childrens.health.qld.gov.au/health-a-to-z/epidermolysis-bullosa 

https://www.eb-researchnetwork.org/research/what-is-eb/ 

https://pubmed.ncbi.nlm.nih.gov/8601736/ 

https://my.clevelandclinic.org/health/body/23204-keratin 

https://link.springer.com/referenceworkentry/10.1007/3-540-29623-9_2980 

https://www.ncbi.nlm.nih.gov/books/NBK441980/ 

https://dermnetnz.org/topics/the-structure-of-normal-skin 

https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/severe-recessive-dystrophic-epidermolysis-bullosa-rdeb/ 

https://medlineplus.gov/genetics/gene/col7a1/ 

https://medlineplus.gov/genetics/condition/epidermolysis-bullosa-simplex/ 

https://medlineplus.gov/genetics/condition/junctional-epidermolysis-bullosa/ 

https://medlineplus.gov/genetics/condition/kindler-epidermolysis-bullosa/ 

https://www.mayoclinic.org/diseases-conditions/epidermolysis-bullosa/symptoms-causes/syc-20361062 

https://my.clevelandclinic.org/health/diseases/17792-epidermolysis-bullosa 

(00:05):
These blisters, which appear on her hands, feet and mouth, seem to emerge wherever her skin
experiences friction or after minor bumps. You've observed that they take longer to heal than you
would expect, adding to your anxiety. While attending a baby group, you couldn't help but
notice that Amelia is smaller than the other babies there, which has heightened your concern.

(00:25):
Driven by your love and concern for her wellbeing, you decide to bring it up with the paediatrician.
Hello and Welcome to Anatomy Of Illness. Today's episode is about Epidermolysis

(00:49):
Bullosa. Before we get into the condition, we are going to start with the history. So why do we know
Epidermolysis Bullosa exists? In this episode, I may also refer to the condition as its abbreviation,
EB. We begin in 1870 with the Austrian dermatologist Ferdinand Ritter von Hebra. He is
credited with the first possible description of the condition. This is where he described a congenital

(01:11):
condition that caused blisters in the skin, congenital being a condition you were born with.
This condition was hereditary, meaning it ran in the family. However, this is not when we would get
a name for the condition. The term Epidermolysis Bullosa would be coined 16 years later in 1886 by
Koebner and has been used as a term that encompasses several skin conditions with

(01:32):
similar types of symptoms. In 1898, Hallopeau also described some of the features found in one
of the types of EB, this being Epidermolysis Bullosa Simplex. However, the understanding of
what was going on in the condition structurally would not occur for many more years. In 1913,
EB would be associated with a risk of developing certain cancers, specifically squamous cell

(01:55):
carcinoma. In the 1960s, with the use of technology, specifically transmission electron
microscopy, this was used to study the ultra-structural abnormalities. In these cases,
a better understanding of what was going on would occur and also a division into three different
major classifications within the condition would occur. These classifications had to do with where

(02:16):
the tissue separations were occurring. These classifications were simplex, junctional,
and dystrophic. In the 1970s, we would get an even better understanding as to why these separations
at these levels were occurring. This also used transmission electron microscopy for discovery.
So they found that in Epidermolysis Bullosa Simplex, there were abnormalities in the keratin

(02:37):
filaments. In junctional Epidermolysis Bullosa, the hemidesmosomes were found to be affected.
And in dystrophic Epidermolysis Bullosa, the anchoring fibrils were found to be abnormal.
Keratin filaments are a type of protein that help form the hair, nails, and what is important in
this case, the outer layer of the skin. Keratin is important in keeping the skin strong and helping

(03:00):
wounds heal. Hemidesmosomes are a multi-protein structure that adheres the epithelial cells to
the basement membrane. The basement membrane lies between the epidermis and the dermis.
The epidermis is the top layer of the skin. Anchoring fibrils attach the dermis to the
basement membrane. In the 1980s, through the use of antigen mapping, the discovery of antigens

(03:21):
involved in EB made the diagnosis of the condition and typing easier for doctors.
By the end of the 1990s, 10 genes that could cause EB had been identified. This would set up
the foundation for specialized care based on the genetic defect causing the condition. In 2006,
the first gene therapy was performed on a patient with junctional EB by Mavilio and colleagues.

(03:42):
In 2007, a fourth condition was included as part of the EB conditions. This was Kindler syndrome.
Also in 2007, Nate Liao, a person who had the recessive form of dystrophic EB,
received a bone marrow transplant performed by the highly respected surgeon John E. Wagner.
The treatment was successful. This led to a trial with seven other children who had

(04:04):
the recessive form of dystrophic EB, having bone marrow transplants. It was somewhat successful.
However, two of these children passed away due to complications with the trial, one being in
the pretreatment transplant phase of the trial and the other six months later due to transplant
rejection. Through recent years, many trials of gene therapies, stem cells, and wound treatments

(04:25):
have occurred allowing for better treatment of the condition. So what actually causes
epidermolysis bullosa? Currently, 20 genes have been identified that cause the condition.
This occurs when there has been a mutation in the genes, but depending on the type of EB depends on
the gene that will cause the mutation. For those with both the dominant form of dystrophic EB and

(04:46):
the recessive form of dystrophic EB, the gene that causes this condition is the COL7A1 gene.
This gene is known as the collagen type 7 alpha 1 chain gene. It makes a protein that is necessary
for the making of collagen type 7. This is important in the anchoring fibrils, which are
affected in this form of EB. This causes blisters in the dermis layer, which is the lower layer of

(05:08):
the skin. It is below the basement membrane. With EB simplex, there are several different gene
mutations that can cause the condition. Most of these occur in the KRT5 and the KRT14 genes. So
these are the Keratin 5 and Keratin 14 genes. This is mostly a dominant type of EB, but some of these
gene mutations can be recessive. This form causes blisters to occur in the epidermis, so the top

(05:33):
layer of the skin. With junctional EB, there are several different genes that can cause the
condition. The most common are the LAMA3, the LAMB3, the LAMC2, as well as the COL17A1. The LAMA3,
LAMB3, and LAMC2 genes create subunits that are required for constructing a protein called

(05:58):
laminin-332. This is important for stabilizing the skin and helping to attach the epidermis to the
rest of the layers of the skin. With mutations in these genes, it creates a non-functioning protein
and the skin becomes unstable, meaning it gets damaged more easily. With the COL17A1 gene,
this is the gene that makes the Collagen 17 protein. This protein is important for also attaching the

(06:22):
epidermis to the rest of the layers of the skin. With mutations in this gene, the skin is more
easily injured by friction, minor traumas, and blisters easily. And there is also Kindler's
syndrome. This type is very rare and is caused by mutations in the FERMT1 gene. This gene makes the
protein Kindlin-1. This protein is important in keratinocytes. It is important for many

(06:44):
cell functions and the adhesion of keratinocytes. These are the four main types of the condition,
however, throughout the main types, there are about 30 subtypes spread throughout them.
Who does EB affect? Epidermolysis bullosa affects 500,000 people worldwide, which is about 1 in
30,000 people. This makes it a rare condition. This condition affects both men and women equally.

(07:07):
It can occur in any race or ethnicity. How do we test for epidermolysis bullosa? If epidermolysis
bullosa is suspected due to the skin's appearance, there are several tests that can be done to
determine if a child has EB. These include prenatal screening. This is done before the
child is born, so before you even get to look at the skin. This is used in cases where there is a

(07:28):
family history of EB. So if one of the parents has it, or if a sibling has it. There is also skin
biopsies. These are normally skin that is affected, is biopsied, and looked at under a specific type
of microscope to observe the affected areas of the skin. This can help with the typing of the
condition, seeing what proteins are present and healthy, and also gives an idea of what is not

(07:48):
healthy and what is missing. And genetics testing. This is where a blood sample is sent for DNA
testing. This identifies what gene is mutated and most likely causing the condition if we know about
the gene. We will get right into the symptoms and presentation right after this little break.
If you're enjoying this episode and would like to check out the notes,
you can check them out on BuyMeACoffee.

(08:21):
What symptoms may you or your child have if you have Epidermolysis Bullosa?
As there are 4 main types of Epidermolysis Bullosa and about 30 subtypes of the condition,
symptoms will vary depending on the condition, the severity, the gene causing the condition,
and even on the personal experience. Some of the more common symptoms of EB include
thin looking skin, fragile skin that blisters easily, this happens especially on the palms

(08:44):
of the hands and the soles of the feet. The skin in this condition is very fragile,
like the wings of a butterfly, which is why it is often referred to as butterfly skin,
or children with this condition are referred to as butterfly children, because the layers of the
skin do not stay together. But anyway, back to the symptoms. Itchy painful skin, tiny pimple-like
bumps, these are called milia. You may also have nails that are thick or unformed. You may

(09:10):
have blistering on your scalp and hair loss, this is called scarring alopecia. You may also have a
difficulty with swallowing, this is dysphagia. And you could also even have dental issues,
such as tooth decay, or even teeth that are of an irregular size, normally smaller than you
would expect. What complications should a doctor be aware of if their patient has Epidermolysis

(09:31):
bullosa? Complications can vary based on the type of EB. Some of the complications people with
Epidermolysis bullosa may face are infections. Due to the frequent skin blisters, people with
the condition have a higher risk of infections. Bloodstream infections, this is also known as
sepsis, as this is when bacteria enters the bloodstream and spreads throughout the body.

(09:52):
This can spread rapidly and can lead to shock and organ failure. This can cause death, fusion of the
fingers and changes in the joints. Severe forms of EB can lead to the fingers or toes binding
together. It can also lead to an unusual bending in the joints, this is known as contractures.
These normally affect the fingers, knees and elbows. Problems with nutrition. EB can cause

(10:14):
blisters to form in the mouth and even in the throat. This can lead to malnutrition and anaemia.
In children, this can also lead to delayed or slowed growth. Dental problems. Tooth decay and
other issues with the mouth tissues like blisters in the mouth can be common for certain types of
EB. Cancer. Certain types of EB have a higher risk of developing a type of skin cancer known as

(10:34):
squamous cell carcinoma. Death. Infants with severe junctional epidermolysis bullosa have a high risk
of death. This is due to the high risk of infections from the blistering of the skin as well
as the loss of fluids that these blisters create. This condition also causes blisters in the mouth
and throat. This can make it difficult to eat and even breathe. How do we treat epidermolysis

(10:54):
bullosa? Currently we do not have medications that can treat the condition. However, there are many
that are currently going through clinical trials. Currently medications that are used in the
condition are used to manage infections. So these are antibiotics. Surgeries can be used to help
manage some aspects of the condition. These include widening the oesophagus. The blisters
caused by the condition in the oesophagus can cause narrowing of the oesophagus. This makes it hard to

(11:19):
eat so this can be surgically widened. They may also recommend placing a feeding tube. This is a
gastrostomy tube. This can help with nutrition and weight gain as the food is delivered directly to
the stomach. Skin grafting. This will be done in cases where the blisters have affected the function
of limbs such as the hands. A surgeon may also recommend surgeries to correct the contractures
which are the abnormal bending of the limbs. They may also recommend surgical corrections for

(11:43):
abnormal limb fusions at the fingers and at the toes. These will be recommended if movement is
restricted. The condition is predominantly cared for by ensuring the blisters stay cleaned,
bandaged with specific moisturizers and monitored for signs of infection. There are no famous people
with the condition. However, if you would like to watch a documentary there is The Boy Whose Skin
Fell Off. This is a TV movie from 2004 that did not sugarcoat it with the name. It follows Johnny

(12:08):
Kennedy, not the former US president. He had dystrophic epidermolysis bullosa which led to his
skin falling off and also led to Johnny getting skin cancer. This film was a celebration of his
life which he faced with humour. There is also My Skin is Killing Me. This follows two people,
a 5 year old boy named Payton in America who has epidermolysis bullosa and Cheng in China who has

(12:29):
ichthyosis which is a different condition that also affects the skin. This film follows their
experiences, how they are treated and what their illnesses are like. It is informative with the
differences in their conditions and how important the skin is as a barrier for infection. If you
would like to check out a foundation there is for those in America, DEBRA US. This foundation is
part of DEBRA International. This foundation provides support for those living with epidermolysis

(12:53):
bullosa. They provide direct to patient services, access to wound care supplies and access to
specialist nursing care. They also hold conferences that provide the most up to date information for
both healthcare professionals and patients and their caregivers. For those in the UK there is
the Cure EB Foundation. This foundation works to fund research into potential treatments for
types of epidermolysis bullosa to hopefully provide symptomatic relief and also in the future

(13:18):
a cure. For those in Australia there is the EB Research Partnership. They aim to find treatments
for the condition and hopefully a cure for epidermolysis bullosa. They fund research into
finding these treatments. If you want to check out the sources, social media links or any other links
you can head to anatomyofillness.com. If you enjoyed this episode and would like to hear more
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(13:39):
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YouTube. Otherwise stick around for the next episode. Did you know the average person has

(14:01):
300 million skin cells? It also accounts for around 15% of your body weight.