>> Good morning.
Thank you for the introduction.
I hope I can live up to the rock star
preview.
I (clears throat) participated in my first
Women's Journey this past fall
and it was really wonderful.
And I think a lot of us who go into medicine
do so because we really want to teach
and empower our patients
and the Women's Journey really allows us to do that
outside of the clinic.
And so,
I hope we can do that today as well
for this smaller group.
I am very excited to share with you two hot topics
and these are hot topics not just in Dermatology,
but also in many fields in medicine today.
And hopefully you've had heard of these
and have some familiarity with them.
But the first topic is how inflammation in one part
of the body is associated
with what we call "systemic inflammation"
and that's inflammation throughout the rest of the body.
The second concept is how our microbiome,
and that is the entirety of trillions of microbes
that live in us and on us,
can impact our health.
So, I will illustrate these concepts
by taking you on a journey,
because this is a Woman's Journey,
with Sally and Eleanor, two patients
with common skin diseases, psoriasis and eczema.
And those diseases have had an expansion of knowledge
that has changed not only how we understand
what drives the conditions to start,
but also how we treat them.
And of course, their names have been changed for privacy,
but go ahead and put on your white coats.
I've just graduated you all from medical school.
(crowd laughs softly)
And come along with me as these patients' stories unfold.
So, we'll first meet Sally.
She's a 62-year-old woman,
and she reports that for the last year she's had
red, raised legions on the back of her scalp and her elbows
and knees.
They're occasionally itchy.
She's tried multiple different types
of moisturizing lotions,
but nothing's really working.
Sometimes it gets better,
but usually there's always some kind of rash on her body.
She's never really had a rash like this before
the year ago when it started.
But she does remember her father
maybe having a rash like that.
She does not take any medications.
She's healthy.
She does have mildly elevated blood pressure
and is slightly overweight,
and she's been trying to manage these problems
with a healthy diet and trying to exercise
two to three times a week.
When we examine her,
we see what she described:
pink-to-red scaly plaques on the back of her scalp,
both of her elbows,
and the fronts of her knees.
So we diagnosed Sally with chronic plaque psoriasis,
which is the most common type of psoriasis.
And we explain to her that 1 to 2% of the population
has psoriasis.
Men and women are affected equally.
And psoriasis usually appears at two age ranges:
one is the teens to 20's,
and one peak in the 50's to 60's.
So, she fits with sort of the later onset peak.
And like Sally,
about a third of patients with psoriasis
do have a family member also who have
had a history of psoriasis,
suggesting that it arises from a combination
of genetic and environmental factors.
We take a look at Sally's nails
because we know that psoriasis can affect the nails
and her nails actually appear normal.
We then ask Sally about joint pain
since about 30% of patients
with psoriasis can have an associated arthritis.
And she says:
yes, she has right knee pain
and she always attributed it just to her age,
but she's never actually had it evaluated
by a doctor before.
We make a referral to a rheumatologist
to evaluate Sally for psoriatic arthritis.
Now the association between psoriasis and arthritis
has been recognized for decades.
And when we have an association like this in medicine,
we call it a "comorbidity"
and that is the simultaneous presence
of two chronic diseases or conditions in one patient.
In the last five years,
our understanding of the comorbidities with psoriasis
has literally exploded.
We have recognized that psoriasis
has many other significant comorbidities in addition to
just arthritis
and particularly with regard to cardiovascular disease.
For example,
patients with psoriasis have a 1.6-fold increased risk
of stroke just because they have psoriasis.
There's a 1.7-fold increased risk of a heart attack
compared to people who do not have psoriasis.
Additionally,
patients with Psoriasis have a 2.3-fold increased risk
of Metabolic Syndrome.
And Metabolic Syndrome is what we call
it's a constellation of diseases,
including abdominal obesity,
insulin resistance,
high blood pressure,
and high cholesterol.
And all of those things individually
and in combination
can also increase cardiovascular disease risk.
So, this is exploding
and there are also a lot of other associations
like depression
and other types of mental illness as well.
I'm going to sort of focus
on the cardiovascular disease comorbidity.
So while these connections are being made clinically
between Psoriasis and these other comorbidities,
investigators have also been working really hard
to try and understand what,
at the microscopic level,
is happening in the skin of psoriasis patients
as compared to their unaffected skin.
And the key finding really seems to be
the presence of inflammatory cells,
mostly T-Cells.
This is a T-Cell driven inflammatory disease.
And what we know is that
these T-Cells are not only active
in the inflamed psoriasis skin,
but also are circulating
through that patient's body
and they were not sure what is the chicken and the egg,
but they may be driving not just the psoriasis in the skin,
but also the cardiovascular disease
that these patients have.
So when I was a resident even,
not that long ago,
we once considered (laughs)
and I'm a dermatologist,
I know,
tried Botox and everything,
but it really wasn't that long ago,
but when I was a resident,
we considered psoriasis a disease pretty much limited
to the skin and joints.
But now we consider psoriasis a systemic disease.
This is inflammation that can affect
the patient's entire body.
So when we're talking to Sally,
I can't just treat her skin and send her
to the Rheumatologist for her joints.
I also have to talk to her and educate her
about her cardiovascular risks as well.
And usually patients like Sally
are actually really interested in hearing about these,
just like you guys are.
People really do want to own their health
and want to know about it
and so we say
"go to see your primary care doctor
or even a cardiologist to actually maybe get treated
for your high blood pressure
and try and do what you can to lose weight
because it actually really may have a significant impact
on your overall health
because of your underlying psoriasis."
For other patients,
this may include smoking cessation counseling,
counseling on decreasing their alcohol intake,
and a variety of other factors.
So our improved knowledge of the inflammation,
which drives psoriasis,
has also allowed us to develop new treatments,
which really, specifically target that inflammation.
And an important question Sally is going to ask us
is whether if she takes one of these newer medications
that specifically targets this inflammation
to treat her skin and possibly her arthritis,
will this lower her cardiovascular risk as well?
And that's a good question.
So if we use these anti-inflammatory treatments,
will she also benefit from a cardiovascular standpoint?
And this is actively being investigated.
There are studies just within the last year
that have been published that do suggest
that certain psoriasis treatments,
that do target very specifically the inflammation
that drives the condition,
may lower some of cardiovascular disease risk markers
and that is really exciting.
So we're not just going to help her skin and her joints,
but we may actually also reverse some of the
cardiovascular risk.
So she's going to talk to her primary care doctor
about her blood pressure.
She's going to talk to her Rheumatologist.
And we will kind of circle back to Sally,
but really her story illustrates how inflammation
in one part of the body can reflect systemic inflammation.
And thus how a skin disease
like psoriasis
can really have significant implications
for a patient's overall health.
OK we're ready for the next patient.
We're only 30 minutes behind in clinic.
It's not that bad.
(crowd laughs)
Now you guys know why we run behind.
There's a lot to get in a 15 minute visit.
So in our next room,
we meet Eleanor.
And Eleanor is eight-year-old girl with atopic dermatitis.
Atopic dermatitis is the most common type of eczema,
and that affects about 10% of the population.
And as is typical,
Eleanor's eczema showed up in infancy
around when she was five months old.
And her eczema has changed somewhat as she's gotten older.
It used to affect her face and her wrists,
and now it affects more her neck and her inner elbows
and the skin behind her knees.
And she's in the clinic with her mom today
who helps tell us what's going on.
And we also note in her medical record
that she has seasonal allergies
and that she has a maternal uncle
who also had eczema and has food allergies.
So Eleanor seems to be doing well today,
but she still reports a lot of itching
and her mom says the itching is making it hard for her
to concentrate in school
and she's having trouble sleeping at night
because of it as well.
And they've been really trying to keep up a good routine
of taking care of her dry skin,
but her mom seems to think that Eleanor's eczema
just seems to have a mind of its own.
That no matter what they try to do,
it still seems out of control.
Now over the past year,
we have seen Eleanor four times in the hospital.
She's what we call a "Frequent Flier"
but you don't get any miles for that, unfortunately.
(crowd laughs faintly)
And every time she's come in,
it's because her eczema has flared so severely
that it results in what we call "erythroderma"
which is total body redness.
When a rash
and it can be from other conditions
so psoriasis actually can cause erythroderma
but eczema is a common one and it's total body,
head-to-toe
red,
rashy body.
And it's so severe,
patients can't really control their temperature,
they lose fluid,
so they really need to be hospitalized for that.
And so every time she's been hospitalized,
she's missed school,
her mom misses work,
her siblings have to go stay at the aunt and uncle's house.
So Eleanor's eczema is really turning
her and her whole family's life completely upside-down.
And we've also noted when she's been admitted
to the hospital all these times
that when we culture her skin,
her bacteria "staph aureus" is growing.
OK?
And so part of her regimen,
in addition to intense treatments with topical steroids
and we do these wet wraps
where we get the patients wet
and we cover them with steroids and wrap them up.
But part of it has been oral antibiotics
to treat the staph infection on her skin.
And Eleanor's case is not unusual.
We have known
again for years
that patients with eczema have an impaired skin barrier
and we hypothesize that that impaired skin barrier
led to an increase in skin infections.
However,
we are just now starting to put the pieces together
as to why this is happening.
So through studying atopic dermatitis
and the propensity of these patients
to develop various skin infections,
we have learned about the skin microbiome
and its role in impacting disease.
So the human microbiome is the collection of microbes
including bacteria and viruses that inhabit us.
We're not alone.
You're never alone.
You think you're alone,
you're never alone.
Although microbial cells are much smaller than a human cell,
together they may weigh up to five pounds in an adult.
I always knew there was a reason we could never lose
that last stubborn five pounds.
(crowd laughs)
OK.
But these microbes do a lot for us.
They help us digest our food,
they produce vitamins,
and they can prevent infections,
among other functions.
Recent advances in DNA technology have actually allowed us
to really identify these microbes.
Because most of them you can't grow in a culture.
You can't grow from just swabbing the skin.
And one important finding is just how extensively varied
the microbiome is in individuals
even without any particular disease.
So one person's microbiome on their skin
can be very different from another person's,
but investigators have also started
to look at particular diseases and to say
"in patients with eczema and patients without eczema,
how do their microbiomes compare to each other?"
So interestingly in atopic dermatitis,
affected skin with eczema actually has
decreased microbial diversity
as compared to unaffected skin.
So there's not as many microbes in that skin.
Along with that,
there's a higher rate of staph aureus in that skin.
And studies have beautifully shown these beautiful graphs
where patients with eczema
they kind of swab the skin over time
and as the staph aureus counts start to increase,
the flare of eczema follows.
OK so we get a sense of timing
of this.
So what we saw with Eleanor,
with her concurrent staph infections
every time her eczema flares,
is common
and somehow the combination of this impaired skin barrier
that patients with atopic dermatitis have
and the presence of less microbial diversity
with the predominance of staph aureus being there
on the skin is actually driving the inflammation
that leads to eczema.
So historically eczema treatments have really focused
on improving that skin barrier
and reducing inflammation on the skin
as well as treating any super infection that may occur.
But understanding the microbiome
may present an opportunity
for us to focus our treatment
on maintaining the microbial diversity seen
in normal skin, not affected by eczema.
So for example,
why not take these good, diverse bacteria,
put them in a lotion,
and give it to our eczema patients to put on their skin?
And this is actually currently being studied
in a Phase Two trial right now.
And that would really radically change
our treatment approach to patients with eczema
because we would be really trying to
prevent the flares and the exacerbations
that just lead to not just a miserable life
and not sleeping
and not studying in school,
but also hospitalizations where they're out of school
and the parents are out of work.
There are also studies right now asking whether exposing
just healthy baby skin to diverse bacteria
can even prevent atopic dermatitis
from developing in the first place.
So we are really at the tip of the iceberg of all this
and it gets even more complicated
when if I tell you that patients with atopic dermatitis
about a third of them have food allergies
and the whole role of the gut microbiome
and food allergy development is also exploding
and how the skin microbiome and the gut microbiome
might even talk to each other
is also a huge, new, unfolding field.
So by studying the role
of the skin microbiome in atopic dermatitis development,
it's really helped us to learn about the interaction
of the microbiome in eczema
as well as other types of eczema that people develop,
not just atopic dermatitis,
and other skin diseases as well.
(clears throat)
So in conclusion,
we've always known as dermatologists that there's more
to skin disease than what superficially meets the eye.
And through our recent advances in understanding the link
between skin and inflammation and systemic inflammation
as well as our discovery of the skin microbiome
and its role in keeping us healthy,
we are getting better
at being able to take care of our patients,
like Sally and Eleanor.
So,
thank you for your attention and I'll
happy to take questions at the end.
(crowd applauds)