An Itch That Must be Scratched: Questioning the Genetics of Atopic Dermatitis

Overview of Research:
Atopic dermatitis is a debilitating disease that affects both children and adults. A
large amount of the worlds population has atopic dermatitis, which decreases their
overall quality of life, and in some cases, causes disability in adult cases. The exact cause
of atopic dermatitis is not entirely know, although genetics is known to play a part in the
predisposition for the disease. By studying and cataloging the genetic anomalies in atopic
dermatitis patients, specifically those with severe cases that contain recurrent infections,
personalized medicine can be created to assist this group of people who otherwise would
not receive effective treatment.
Background and History of the Issue:
The basis of predisposition to almost every disease lies in a persons genetics. In
the case of 20% of children and 10% of adults across the world, genetic code
predetermines atopic dermatitis (National Institute of Health). Atopic dermatitis, or AD,
falls under the wide umbrella of eczema. It is characterized by scaly and red skin
accompanied by weeping fluid and bouts of itchiness. (National Institute of Arthritis and
Musculoskeletal and Skin Diseases, 2014). This phenotype of extreme reactions stems
from genotypes so diverse that it is difficult to find the mutation or mutations that are
responsible for the disease. The strongest commonality between 30% of people living
with AD is the FLG gene mutation (National Institute of Health). This mutation seems to
be the clearest cause of AD as it produces fillagrin protein, or the protein that hydrates
and protects the skin and also attaches keratin to skin cells. This connection would
explain the prevalence of AD as association with the FLG gene makes AD autosomal
dominant (NIH-9/30). This mutation is only one of many, however, that explain the
causes of many facets of AD; genes for the immune system could explain high levels of
inflammation while other genes connected to the nervous system could explain abnormal
itching.
It is important to note that in more serious cases of AD, recurrent bacterial
infections are also a symptom. And while these infections may be causes of continuous
itching and scaling of the skin, some AD patients are predisposed to having a higher
chance of being infected because of their genetics (Ong, Leung, 2016). The most
common bacterial infection to appear in AD patients is S. aureus, but other viral
infections actually have the ability, assisted by genetic mutations, to transform an AD
patients form of disease. Those AD patients who become infected with Herpes Simplex
Virus are often diagnosed with eczema herpeticum (characterized by recurrent infections,
septic shock, and fever) while others who become infected with smallpox may be
diagnosed with eczema vacciticum, which is oftentimes fatal (Leung- 10/10). In fact,
eczema vacciticum has played and continues to play an important role in history,
especially American history. People with AD cannot receive the smallpox vaccine as it is
unclear which AD patients could get eczema vaccinatum. While smallpox was eradicated
in 1979, strains of the disease are still held by the United States and Russia, which raises
the issue of bioterrorism. If smallpox were to be released into either population, those
with AD would have no medical means of protecting themselves by chance they may
contract eczema vaccinatum (Engler, Kenner, Leung, 2002).
Problem Statement and Rationale:
Those patients with particularly rare cases of AD spend a large portion of their
lives in clinical care. There have been topical and oral treatments that reduce the amount
of swelling, itching, and infections in mild cases, but the most severe cases have yet to
benefit entirely from those treatments. By researching the individual genetics of patients,
personalized care treatments can be made so that each patient has a regimen specific to
them. In the end, this research would be improving these individuals overall quality of
life. In addition, the threat of smallpox as a bioterrorism tool would be diminished. By
genetically identifying the few individuals who are more at risk for eczema vaccinatum,
those AD patients who are not at a genetic risk would be able to receive their smallpox
vaccinations. Research would still have to be done to assist those still at risk for
contraction, but a large portion of the population, especially the military population,
would be put at ease if smallpox were to ever break out.
Research Question and Hypothesis:
Question: What genetic anomalies in this individual associate them with their type
and severity of atopic dermatitis?
Hypothesis: The phenotypic mutations that differ in this individual versus other
individuals with atopic dermatitis most likely result from genetic mutations in the
interferon gamma gene in this patients genome.
Basis of Hypothesis:
The genetic code that determines the basics of atopic dermatitis is usually very
similar in all AD patients, such as mutations on the FLG gene. If novel mutations were to
be found in this individual, they would affect the genes that code for signaling proteins,
or they would even affect non-coding genes that regulate exonic function. Because this
individual has eczema herpeticum, there is high likelihood that their novel mutations
occur in genes that code for immune system signaling proteins, as eczema herpeticum is
so rare, even in AD patients. The interferon gamma gee codes for signaling proteins that
respond to the attack of pathogens. These signaling proteins would have to be
compromised in some way to allow herpes simplex virus to morph into eczema
herpeticum in this patient, so it is highly likely that the novel mutations are concentrated
in the interferon gamma.
Research Design:
My research will be quantitative as I will be conducting data analysis on an
individual with AD and eczema herpeticum. It will mainly be causal-comparative
research as this individual already has the disease. The research I do additional to this
primary data collection of data analysis will allow connections to be made between the
cause and effects of this persons genetic code.
Operational Definitions:
Genetic anomalies: mutations specific to the individual
Type: specific recurrent bacterial infection as well as severity of the case of AD
Severity: Can be measured in IgE serum levels, rate of bacterial infection, time
between infections, width of affected areas, amount of uncontrollable itchiness
(usually on scale or 1-12)
Novel: specific/unlike any other
Product Overview:
I intend to create a childrens book on the topic of atopic dermatitis, as children
are the largest group affected by the disease (Leung, 2013). People are often diagnosed
with atopic dermatitis at a young age, and there are psychological affects to those who
have very severe cases and a decreased quality of life as a result. By introducing a
childrens book specific to these individuals that are diagnosed at a young age, these
patients may feel validated when they find the cause behind their disease when written in
simpler jargon. These books could be placed in waiting rooms of doctors offices so
children and their parents could read them while awaiting treatment or diagnosis. This
method would target those children and their parents who are wary after the diagnosis of
eczema or AD, especially for those who have to deal with severe cases. The product
could be read and then evaluated by parents who may have thought the book was helpful
in educating their child on their disease.
Logistical Consideration:
There would be a cost to printing this product, although the exact cost is not yet
known as a number of books to be distributed has not been decided. I would also have to
ask permission to place these books in medicals centers, most likely in pediatrician
offices. I have already received confirmation that I can utilize the data analysis I will
collect as primary source in my research. In third quarter, a timeline will be added that
outlines the data collection, products development, and audience distribution.