November 26, 2025 • 34 mins
Dermatologist and clinical researcher Dr. Michael Bernhardt joins Dr. Erich Schramm to unpack the rapidly evolving science of atopic dermatitis. The two doctors discuss the symptoms, science, and treatments for atopic dermatitis, including how much clinical research has changed the landscape and improved outcomes. The two get into how the immune system drives the disease, and how new therapeutic drugs target those systems in way thats more than just skin deep.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Announcement (00:00):
Welcome to MedEvidence, where we help you
navigate the truth behindmedical research with unbiased,
evidence-proven facts, hosted bycardiologist and top medical
researcher, Dr.
Michael Koren.
Erich Schramm, MD (00:11):
Hello, and welcome back to another episode
of the MedEvidence Podcast.
I'm your host, Dr.
Erich Schramm.
I'm a board-certified familyphysician and longtime clinical
research investigator with theENCORE Clinical Research Group.
And I'm very excited to besitting across the table again
from one of my favoritedermatologists and esteemed
clinical research colleagues,Dr.
(00:31):
Michael Bernhardt.
Welcome back to another episodeof the MedEvidence Podcast.
Michael Bernhardt, MD (00:36):
Great to be back.
It's been a little while.
Erich Schramm, MD (00:38):
Yeah, it has been.
So just getting caught up onthings.
We've done a couple of few ofthese before.
Michael Bernhardt, MD (00:44):
Right.
Erich Schramm, MD (00:45):
And remember the kind of the origin story
for this was, you know, onFridays, we have opportunity to
work together, collaborating onpatients and studies.
And it came out of that that,you know, we spent a lot of time
discussing, you know, topics,clinical research reports, and
(01:06):
all the things that are comingdown the pike.
And people realized that, youknow, we'd get into very
detailed descriptions anddiscussions about, you know,
disease pathways, and it wasvery educational.
And they said, hey, you know,you guys should go and do a
podcast because you know, wejust we just like hanging out,
two docs, talking about, youknow, research and talking
(01:29):
about our patients.
And sure enough, and I lookedat Mike and I said, gee, Mike,
we should do some podcasts.
And I said, Well, how manypodcasts had you done at that
time?
And I believe your answer was
I think I had a my grand totalwas um zero.
Right, it was zero, somewhere between zero
and one.
And then the question was zero,right?
How many podcasts I'd actuallyhosted?
(01:50):
And the answer was for me a bigzero.
And so based on that kind ofexperience, we thought it would
be a great idea to plungeforward and do these kind of
podcast series.
And I'm, you know, I'm kind ofsaying that in a facetious way,
but quite honestly, you know,you really have a, you know,
you're not just a dedicatedclinician, but you're a clinical
(02:11):
researcher, an educator.
And so, you know, you when youcome into the office, um, I feel
like you really do bring a lotto the staff, including myself,
but also to the patients.
You know, you really do havequite a very holistic view of
patient care, and so I reallyreally admire and respect that.
Michael Bernhardt, MD (02:32):
As do you.
Erich Schramm, MD (02:33):
There you go.
Michael Bernhardt, MD (02:34):
Right back at you.
Erich Schramm, MD (02:34):
Right back at you.
Back at you, buddy.
So today we're gonna be talkingabout atopic dermatitis.
And, as you like to do withthese talks, you always do a
great job, kind of foundational,explaining a good definition
for atopic dermatitis, and thenmaybe running through, you know,
the epidemiology, etiology,and then you know, maybe even go
(02:56):
back and forth on a fewdifferent things.
Michael Bernhardt, MD (02:57):
Sounds good.
So we've come a long way withatopic dermatitis, and and
honestly, thanks to clinicalresearch, you know, and and you
know, it's so popular to bashthe pharmaceutical companies.
But like I tell the residents,you could be the best carpenter
in the world, but if you don'thave a hammer, nails, a skill
saw, and a level, you're notgonna be able to do anything.
(03:20):
And without the companiesactually make the drugs that we
can use, you know, we're back inthe Stone Age.
So we've had a lot of reallygreat progress with Atopic in
about the last eight or tenyears.
You know, they've drilled downand kind of found some very
significant pathways that drivethe disease condition.
(03:42):
You know, Atopic is known,quote unquote, as the itch that
rashes, right?
I think that's from thetextbooks around back when when
I had a full head of hair.
And I think our next talk'sgonna be about hair loss.
Erich Schramm, MD (03:56):
It's gonna be a hair loss.
I mean, you know, it's reallyinteresting.
You that's that's the phrasethat comes to mind because I was
one of your residents at onetime, and that was one of those
clinical pearls that stuck in myhead and found it very helpful,
you know, throughoutthroughout my career.
So I that's the great greatpearl, right?
Michael Bernhardt, MD (04:11):
Yeah, a lot of times each will precede,
you know, what you can see andwhat you can feel.
Um and it's common, starts inkids, very common in kids.
Usually in the young kids, sixmonths or so, periorificial, you
know, around the mouth, and andthen it spreads to the
anticubital folds, you know, thebends of the elbows, the bends
of the knees.
And these kids can be prettymiserable.
They really can be miserable,and it makes the whole family
(04:33):
miserable.
And you know, back in the day,all we had was topical steroids
and moisturizers andantihistamines.
And and the thing is,antihistamines are only
marginally ineffective in thiskind of itch because a lot there
are other itch pathways betweenthe skin and the brain, you
know, via the spinal cord thatgo through mechanisms other than
(04:56):
histamine.
You know, gavinergic pathways,what they call the cowhage
pathway.
And and we found that a lot ofthese cytokines or these
cycling intermediaries that helpstart the fire that that
transmits itch to the brain, aretotally independent of
histamine.
Right?
So we have molecules likeinterleukin 31, which is a
(05:19):
primary pruritogen of the skin,molecules like interleukin 4 and
interleukin 13, which drive thewhole inflammatory cascade.
And now they're they'restarting to drill a little
deeper and they're looking atother molecules like one of the
studies that we're trying toget, which is a combination of
blocking interleukin 4 andblocking another molecule called
TSLP.
(05:39):
And I always, always, alwaysmutilate the real name of this
thing, you know.
So I I'm just gonna stick withTSLP.
It's like FOMBO, strombo,fymbic, strombic, lymphopuetin,
or something like that.
That's right.
Erich Schramm, MD (05:52):
Sound sounds like a little bit this afternoon
we're gonna sit down and
Michael Bernhardt, MD (05:56):
I've tried to study it a hundred
times.
I still mutilate that.
But TSLP, IL-25, and IL-33 arewhat are called uh alarmins,
A-L-A-R-M-I-N-S.
And alarmins are these littlecytokine fragments that are
released with any kind ofirritation to the epidermis.
Right.
And they act like as the alarmclock.
That's why they call themalarmins, and tell the rest of
(06:18):
the inflammatory cascade, hey,wake up, there's something going
on here that doesn't belong,and it triggers the whole itch
scratch cycle.
So uh right now we have greatdrugs that are FDA approved down
to age six months of age.
For example, a drug likedipolumimab, FDA approved down
to six months of age.
It's an injectable and itworks great at shutting the
(06:41):
process off.
Erich Schramm, MD (06:42):
That's IL-4 & IL-13.
Michael Bernhardt, MD (06:44):
It blocks IL-4 & IL-13.
Erich Schramm, MD (06:46):
Right.
And then the 13 inhibitors, Ithink, are are only FDA approved
down to I have to check and seewhether it's 12 or or whether
it's approved for adolescents orjust adults.
I don't not sure off the top ofmy head.
The 13 inhibitors are alsoavailable.
And then there's a new class ofdrugs for atopic dermatitis
called JAK or JAK inhibitors.
(07:08):
And those are orals.
So in those kids and youngadults who are the ones who
predominantly have this whocan't tolerate an injection,
there's an oral form, but theyou know, there's risk to
benefits, and they all have thisside effect risk.
How do you think in terms ofwhen you're grading severity,
mild, moderate, severe, youknow, do you have some distinct
(07:31):
parameters that you're lookingin that and helping you to
decide what kind of therapiesyou're going to be looking at
with a patient?
Michael Bernhardt, MD (07:37):
And and the way when I'm teaching, when
I'm teaching residents, I alwaystell them that you know a lot
of there's no definitivediagnostic test for atopic
dermatitis.
You do a skin biopsy, it showsinflammation, what they call
spongiosis, which is microfluidin the epidermis.
Um maybe you'll see someeosinophils, which are cells
(07:57):
that get upregulated whenthere's an allergic process.
You can do some blood tests,may help, may not help.
The one I use as a yardstick isIgE.
Yeah.
Right?
And IgE is helpful if it'selevated.
If it's normal, it doesn'treally help you.
And people have to rememberthere's two pathways.
There's an allergic pathway andthere's an auto-inflammatory
pathway that's autonomous fromallergy.
(08:19):
So there's no real diagnostictest.
It's a clinical conundrum.
And you know, you look at theperson, you see, uh, you know,
are you itching?
Well, if someone's sittingthere scratching themselves to
death, it's kind of a sillyquestion to ask.
But you ask, how bad is theitch?
And criteria for itching is ifthe itch is such that it
(08:39):
prevents the person fromsleeping at night or staying
asleep at night, that's severe.
Erich Schramm, MD (08:44):
Right.
Michael Bernhardt, MD (08:44):
That's severe disease.
Um if it's in an in a kid oryoung adult, if it's impairing
their ability to stay awake andfunction in school, um, if they
can't go with their peers, ifthey're soccer players, they
can't play soccer.
A lot of times this is comorbidwith asthma, so they start
running around, they getbronchospasm.
Um, that's severe.
Right.
All right.
Uh kid's a basketball playerand he can't lift his arm ups to
(09:06):
shoot because his the hisaxillary area is so torn up that
it rips his skin when he triesto shoot a basketball.
Well, that's severe disease.
And, you know, back in the daywith these people, all we had
was topical steroids andantihistamines.
And you know, more often thannot, they did not accomplish the
full task that we wanted tohave done.
Erich Schramm, MD (09:27):
Right.
So, um, and just maybe we cantalk a little bit about how
important it is in terms of skincare and for these patients and
um moisturizers and you know, Imean what what kind of soaps uh
they should use or avoid.
Uh maybe you talk about that.
Michael Bernhardt, MD (09:43):
So the to to get to that answer, you have
to uh visualize the skin aslike a five-layer cake, right?
Think of the epidermis as afive-layer cake.
The basement, the first layeris the basal cells, right?
The basement layer, basalcells.
And the um the next layer isthe squamous cells, then there's
the spinous cells, and it's thegranular cells.
(10:04):
And then on top of the cake,like a thick layer of saran
wrap, you have the the stratumcorneum, which is the outer
barrier.
Right.
Right.
So we always say in in atopicdermatitis as a disrupted
barrier.
And when you think about thatand try to take it out of a
nebulous concept to a concreteconcept, what is disruptive?
Well, you you look at thegranular layer.
(10:26):
The granular layer is calledthe granular layer because, and
this is going to come as a shockto people out there, the cells
have granules in them, right?
Erich Schramm, MD (10:33):
Right.
Michael Bernhardt, MD (10:34):
So everybody recovers.
Erich Schramm, MD (10:35):
Right.
Michael Bernhardt, MD (10:35):
So these cells have granules.
And the problem in the atopicworld is that these granules,
which are important forsecreting uh filaggrin, which is
a structural protein uh for thestratum corneum, and it also
helps with junctional and tyingthe junction, the skin cells
together, or they call itjunctional adherence.
Um and then there's what'scalled the odland bodies, which
(10:57):
secrete um cholesterol andsterols and free fatty acids,
which are like the intercellularcement substance, right?
So when these granular, and weknow that in atopic dermatitis,
these granular cells aredefective.
Uh either A, they're secretingdefective products, um, and or
B, they don't secrete at all,they get jammed up.
(11:20):
Okay.
And when you're not secretingthese sterols or or uh what
they're called ceramides, theskin has a gap.
Normal ceramides run abouttwenty to twenty-four carbon
chains in length.
So think of it as like, I don'tknow, uh a tire chain that has
(11:40):
a certain length.
All right.
Okay.
So for the tire chain tofunction, it's gotta have X
amount of loops to it.
So in atopic dermatitis, it'slike X minus 10 in these loops.
Erich Schramm, MD (11:51):
So these are these are inherent to good skin
health because it maintains theintegrity of the skin in itself.
Michael Bernhardt, MD (11:58):
And even more importantly, sometimes when
these tire chains come out tooshort, they can actually act as
an inflammatory driver and uhand aggravate the situation.
So that's what leads to thisdefective barrier.
So moisturizing is superimportant.
And the reason I always tell mypatients to get a moisturizer
with ceramides is because ifthese kids and young adults are
(12:21):
not producing ceramides in sucha way that they keep the barrier
whole, you need to supplementthat.
So a moisturizer withoutceramides is only kind of
quasi-effective.
Erich Schramm, MD (12:33):
Is that you know if uh if I go to the
pharmacy and I find this easy tofind uh moisturizers with
ceramides, or do I have to lookon the backside and
Michael Bernhardt, MD (12:43):
now they they advertise it because every
you know everybody's kind of hipto the need for ceramides.
Erich Schramm, MD (12:48):
Okay.
So uh that's critical tomaintain um good skin health,
um, moisturizing.
Uh what about soaps?
Michael Bernhardt, MD (12:58):
Uh try to keep them bland.
You know, I'm I'm a big fan ofwhite fragrance-free dove soap.
Okay.
It's got mineral oil in it,which is lubricating.
Um, I'm not really a big fan ofof any fancy soaps that have
fragrance or color or dyesbecause people with atopic
diathesis are more sensitiveanyway.
So things that normallywouldn't irritate you or me or
(13:20):
or you guys in the room, youknow, if you have atopic, it
might set you off.
Right.
So try to keep it kind of onthe bland side.
On the mild side, not the wildside.
Erich Schramm, MD (13:30):
Uh uh shower uh cool or warm?
Michael Bernhardt, MD (13:34):
What any that means so if you take a
shower that's too hot, it'sgonna stimulate those itch
fibers and trigger that wholeitch scratch response.
So try to keep it moderate.
I know on a cold winter day youlove to crank that hot shower
up.
We all do.
And it does.
It feels so good, but if youhave atopic dermatitis, it's
gonna set you off.
Erich Schramm, MD (13:52):
Okay.
Uh good, good food for thought.
Um, the other question that'scoming to mind is um, can can
you describe the like earlyversus late stage disease
processes?
Because you know, at some pointthat you haven't activated so
much of that uh theauto-inflammatory or the the
(14:15):
allergy arm of it, but it itdoes ramp up over a period of
time, right?
Michael Bernhardt, MD (14:19):
Yeah, it's kind of cool because it's a
it's kind of a multiphasedisease, right?
And we know that in the firstphase it's inflammatory, and
then it becomes quote unquotefibrotic.
In other words, the skinthickens up.
And the TH2, you know, there'stwo inflammatory pathways,
right?
At least, I'll say three.
Erich Schramm, MD (14:36):
Yeah, please remind me of those.
So now we've talked about them.
Michael Bernhardt, MD (14:39):
And I'm sure there's going to be a
zillion more, you know, by thetime you guys are my current
age, there'll be a zillion morepathways found out.
But I mean, right now the threemain highways that we look at
is TH17, TH1, TH2.
And remember, there's someplasticity between the TH1 and
the TH2 pathway.
Um so with atopic dermatitis,we're mostly talking about the
TH2 pathway.
(15:00):
And what we find is that one ofthe little interesting things
that we see in some of these TH2diseases, they do end with
thickening or fibrosis of theskin.
Um we know that we're not sureof what what the exact mechanism
of that is, but we know that inpeople with chronic atopic
dermatitis, the skin will whatwe call licinofire, thicken.
(15:21):
Right.
Um now what's interesting isthere is a newer biologic drug,
nemolizumab, which doesn'tblock interleukin-4 or 13, which
are the main drugs that we'vebeen using.
It blocks interleukin-31.
Interleukin-31 is what's calleda pruritogen.
In English, to take it out ofscientific ease and put it in
(15:41):
English, pruritogen meanssomething that makes you itch.
Okay.
Okay.
So interleukin-31 is one of these
primary pruritogens that reallycauses severe itching.
It shares a receptor.
So in other words, when thesecytokines, if you think of
cytokines as a key, right?
They're floating around in yourbody, they're keys.
They're looking for a littlelock to go into in turn, right?
(16:05):
So interleukin-31, that littlekey is looking for its
receptor or its lock.
Well, it shares a receptor withanother molecule.
This is pretty cool.
Called Oncostatin M, which isOncostatin M is a cytokine that
or a receptor site that drivesfibrosis.
It also has other you knowoncologic related properties
(16:28):
that are just kind of beingdiscovered that are not germane
to this talk.
Um but what it what it does isit does stimulate fibrosis.
Erich Schramm, MD (16:36):
At the level of
the receptor level.
At the receptor level.
Michael Bernhardt, MD (16:40):
So that may be one of the you know,
activating IL-31 and oncostatinM may be one of the reasons that
tickles that pathway offibrosis.
So these the couple of thesedrugs have been um FDA approved
not just for atopic dermatitis,but another inflammatory
fibrosing disease calledprurigo nodularis, where people
get these horribly itchythumbtip size lumps on their on
(17:03):
their trunk and on their arm ontheir extremities.
And both these drugs work likea charm in terms of reducing not
just the inflammation, but thethickening and the fibrosis.
Erich Schramm, MD (17:13):
Once a person, say they develop some of
those thicker plaques um thatyou sometimes see, um, is that
reversible?
Can you how do you approachthat?
Michael Bernhardt, MD (17:24):
With one of these injectables, either
with um the 413 or the 13inhibitors or the the 31 OSM
inhibitor.
And that allows the skin tokind of re-engage and restore
kind of a more normal.
You're taking the inflammatory onus
away, and it with time itnormalizes.
Now, thicker fibrotic skintakes more time to normalize
(17:46):
than just quote unquote itchyskin.
With most of these drugs, theitching is gone within a day or
two.
Right.
And that's the main thing.
Because if you're itching, it'snever going to go away, right?
If you if you continue toitchy.
Yeah, the itch relief is a godsend.
You know, we're even seeing itnow with some of the topicals,
the topical JAK inhibitors, youknow, ruxolitinib, and there's a
new one that has some sort ofname that I can't ever remember,
(18:07):
um, "enzupco" or somethinglike that.
But they're topical JAKinhibitors.
And they they're they're greatfor chronic eczema, they're
great for chronic atopicdermatitis.
Um we use ruxolitinib, topicalruxolitinib for um vitiligo.
They stop itch in a matter ofhours.
I mean hours.
They've done studies wherethey've charted it in 15-minute
intervals, and you know, the theuh it's an inverted parabola
(18:31):
and how quickly they respond.
Wow.
Yeah,and we're using a lot of
multisyllable words too.
Erich Schramm, MD (18:36):
No, I get that.
You're must be Friday.
It is.
Well, we like that.
Um and we've done uh and we'redoing studies on ruxolitinib for
hidradenitis suppurativa, bythe way, which was another uh uh
great podcast with you.
So um, and we talked um in thepast, we talked a little bit
about um you've done some reallygood definitions to talk about
(18:57):
um the JAK-STAT pathways um anduh really some great uh ideas
some about understanding uminhibiting all the different
types of inflammatory cytokinesthat that were found in these
JAK inhibitors.
And um and just so that whenyou I think when we left off on
that, that we uh, or at leastyou were saying that that
(19:19):
there's a very high comfortlevel to be using, especially a
topical JAK inhibitor likeruxolitinib, um, we didn't have
any really safety concerns withit.
We thought it was or thought itwas a very safe and effective
treatment.
Um, but you know, you have todo the studies, right?
Yes, you can't.
Michael Bernhardt, MD (19:37):
I mean, all these drugs are are you
know, all drugs have sideeffects.
And when I'm doing talks, Ialways tell people that you
can't skip over important safetyinformation because A, it's
important, B, it's safety, andC, it's information.
Erich Schramm, MD (19:51):
Right,
Michael Bernhardt, MD (19:52):
Right.
So you always have to go overthat.
And and you know as aclinician, you'll see some
regulatory things that sometimesmake sense.
Um but again, as a clinician,you don't always see the whole
regulatory picture.
Right.
So FDA has the same warningsfor the topical ruxolitinib in
terms of of you knowcardiovascular events, D V T,
(20:15):
PE, thromboembolic phenomenathat they do with some of the
oral JAKs.
Um so far there's not aplethora of literature that
really um endorses that.
And you know, I don't again,I'm only seeing it from a
clinician viewpoint, not from aregulatory viewpoint.
But I still um counsel patientsas to the risks, including DVT,
(20:39):
uh deep vein thrombosis,pulmonary embolism, even from
the topical.
Erich Schramm, MD (20:43):
No.
Right.
Um Well, you have to, right,and that's a sign of a good
idea.
I think full disclosure forthose patients.
Michael Bernhardt, MD (20:52):
So the easiest way to think about the
JAKs if you want to kind of putthe JAK-STAT pathway in
perspective compared to blockingthe cytokines.
Erich Schramm, MD (20:59):
Right, which we've talked about before.
Michael Bernhardt, MD (21:01):
But the cytokines is like you're putting
the key in the ignition.
Okay?
If you don't have the rightkey, you can't turn on your
ignition.
Um the JAK-STAT pathway is thatelectrical conduit from the
ignition to the starter of yourcar.
Okay.
All right, and that's the easiest
way to think about it.
Erich Schramm, MD (21:15):
Okay, I like that.
Uh-huh.
Now, so um to that point, andthinking about um the four and
thirteen inhibitors, now we got31 inhibitor.
Um, do you see that see that asbeing a potentially greater
benefit than for the four andthirteen, or is there enough
(21:35):
information out there to to cometo some conclusion about it?
Michael Bernhardt, MD (21:38):
You know, they're all great drugs, right?
And you prioritize based onpatient age and in terms of
what's appropriate for thepatient.
And the comorbidities.
Um, you know, everybody'safraid of these JAK inhibitors,
but there was a study publishedMay, Journal of Clinical
Allergy, that looked atabrocitinib, which is there's
(21:58):
two main JAK inhibitors,pacritinib and abrocitinib, both
great drugs.
They both have done absolutewonders for people.
But this particular study justfocused on abrocitinib.
And they were saying that inthe low dose, the 100 milligram
dose, the risk of cardiovascularand thromboembolic phenomena
were no different in a youngerpopulation, the population under
65, um, which at that age to meis still a younger population.
(22:22):
But in the under 65 population,there was no difference between
the SEER data, the expectedepidemiologic data.
When patients are over 65, thenthe risks start to trend up a
little bit.
Right.
And when you have to go on the higher
dose, the 200 milligram dose,the risks start to trend up a
little bit.
But for younger people on thelow dose, um, based on this
(22:44):
article, the data shows thatthat the morbidity is about
equivalent to what you'd expectin the population.
Erich Schramm, MD (22:50):
Was that, to remind me, was that a kind of a
pan-JAK inhibitor, or is that amore selective JAK inhibitor?
Michael Bernhardt, (22:58):
abrocitinib is more of a selective JAK-1.
I mean, all these you know, allthe drugs have some effect on
multiple JAK sites, but you youlook at how effect how much
upregulation of the other JAKsand the difference between the
JAK 1 and JAK2 upregulation ishuge to the point where it's
really just a selective JAK 1.
Erich Schramm, MD (23:16):
Right.
And maybe, and just remind usum, you know, what are some of
the the bad actor um cytokinesthat are downstream once JAK 1
is is out of the same.
Michael Bernhardt, MD (23:27):
Yeah, I mean so so all these things
you're looking at like ininterleukin 6, TNF Alpha,
Interferon-gamma, uh those thosethere's others, but I mean
bottom line is those guys drivea lot of the inflammatory
cascade.
Great.
So now we've got um so we'vegot uh a number of tools in the
armament for atopic dermatitiswith some uh really solid
(23:51):
approaches with monoclonalantibodies.
We've got oral JAK inhibitors
There was a meta-analysis lastyear that where they looked at
at a upadacitinib.
I think they did 45 studies,15,000 patients, and they found
basically the same thing that inlow dose, the risk, the
cardiovascular and the DVT PErisk was equivalent to what
(24:12):
you'd see in the SEER data.
Right.
And that, you know, when you bump up the
dose, yeah, there's acorresponding increase in risk.
But low dose in a youngerpatient population, you were
pretty much at SEER data level.
Erich Schramm, MD (24:24):
Another uh question that comes to mind, and
um getting back and talkingabout some of the other topicals
out there, maybe you could talkabout the
calcineurin inhibitors and someof the other, you know, uh you
know, we've used andpimecrolimus and some of these
other things.
And if there's were their placefor those
Michael Bernhardt, MD (24:42):
So they're great drugs and they
work and and they're they're anice alternative to topical
steroids.
Um, you know, you you can'tparticularly in young kids,
because young kids have a highsurface to volume ratio.
So if you saturate their skinwith too strong a steroid, you
can get some systemic effects.
Right.
You know, you can get someadrenal cortical suppression.
(25:02):
Um, that's a lot ofmultisyllable words on a Friday
afternoon.
Anyway, you can get someadrenocortical suppression if
you're just bathing the kid inin a mid or higher potency
topical steroid multiple times aday.
Right.
Um so I mean a short blast ifyou need to bulldoze through it
is fine, but if you can switchthem off of that and get the
equivalent of steroid sparinglike we do with orals, with the
(25:25):
topical calcinerium inhibitors,ELIDEL, which is pimecrolimus,
and Protopic, which is uhtacrolimus, you can get pretty
much the same mileage withoutthat steroid risk.
Erich Schramm, MD (25:36):
Right.
And so for the the parents thatare out there listening and
they're like, wow, well, how doyou know uh how much uh topical
steroid is too much or which isyou know what's the right or the
wrong uh topical steroid outthere, I'd say, well, talk to
your informed dermatologist tomake sure that you know if
there's really you know concernsabout that.
So that's that's a that's agood point.
(25:58):
So uh we have a lot of optionsout there um aside from topical
steroids, but like you said,they're always available there
if you need it.
So um we've talked about uhways to keep the skin healthy
and having good skin hygiene.
Uh you've given us some reallygood uh background and talking
about and understanding the uhthe uh interleukin inhibitors,
(26:21):
the monoclonal antibodies.
We talked about um the uh howthe JAK-STAT inhibitors um are
out there and really being avery effective uh element.
Um fantastic.
Anything else that might be outyou see coming down the pike?
Michael Bernhardt, MD (26:37):
You know, we use sometimes left people
take bleach baths, which meansyou take a bathtub full of water
just like you normally wouldand put a cap, maybe two caps,
not a cup, not a C U P, a C A P,a cap or two of bleach.
And the you know, when I tellpeople that they look at me like
I'm either crazy or I have athird eye.
Erich Schramm, MD (26:54):
I've been looking around.
I'm uh maybe there is a thirdeye that is that is a first,
right?
Michael Bernhardt, MD (27:00):
Um and then I always say, well, there's
a reason for it.
And you know, why do we putchlorine, which is bleach, why
do you put it in swimming pools?
Because it kills bacteria.
Erich Schramm, MD (27:09):
Right.
Michael Bernhardt, MD (27:09):
Right?
So on the micro level, if youtake a bleach bath once every
week or two, you're gonna killthat staph that's on the skin.
You know, like I was talkingabout before with the uh
defective granular layersecretions, right?
Normally the skin secreteswhat's called antimicrobial
peptides, which reduce staphflora, and they do things to
make it harder for the staphaureus, which is the main uh
(27:32):
infection driver, to bind toskin.
Well, in kids with atopicdermatitis with defective
granular secretions, not only dothey not have enough
antimicrobial peptides to wardstaph off, they actually have
receptors on their stratumcorneum that encourage staph
binding.
So these kids are more prone tostaph carriage.
Now, when you when you use ableach bath once every week or
(27:55):
two, you're killing thatorganism off in a way that does
not cause drug resistance.
Okay.
And you're not going to put thekid at risk for a cap of bleach
in the tub units.
But um the other point I wasgoing to make is that once you
repair the barrier, when you'reusing the 413 or the 13
inhibitors or the JAKinhibitors, and you repair the
barrier, particularly in thefourth, there's data that shows
(28:16):
that with the 413 inhibitors,um, you actually reduce the
kid's risk of infection becauseyou've reintegrated the barrier.
Erich Schramm, MD (28:23):
Right.
Do you ever see a time whereyou would put somebody on just
oral antibiotics or any kind ofprophylactic or any time, uh any
time if you would consider anycourses for oral antibiotics in
that?
Michael Bernhardt, MD (28:37):
Yeah, when they're if they're starting
to look impetenized, yeah,sure.
Okay.
Sure, sure.
But I would definitely like tosee them do a bleach bath.
And then the other thing toremember, moms and dads out
there, especially if any of youwork with cement, right?
The skin, when you're in ashower or bath, is like wet
cement.
And when you get out of thatshower and bath, you've got
about four or five minutesbefore that cement sets.
(28:59):
And once the skin sets, it'sless effective with the
moisturizers.
So when you get the child,yourself or your child out of
the shower, pat dry, and thenthat's the time to put your
moisturizer right on.
Don't wait 20 or 30 minutes,put it on right after you get
out, and you get a betterresult.
Erich Schramm, MD (29:16):
Wow.
That's that's great.
I mean, that's just greatgeneral, good skin care.
Um back to thinking about umthe JAK inhibitors and the
monoclonal antibodies.
Um, as far as um expectationsfor patients for healing, their
timelines.
Is there one that's a littlequicker than the other, or is it
(29:36):
all about the same?
Michael Bernhardt, MD (29:38):
They're all pretty good.
Uh they're all pretty good.
When you look at the studies,there's a lot of overlapping
data with the low dose JAKsversus the 413 inhibitors.
They're really pretty good.
Um, some studies, some of thedrugs have studies that show
that itch reduction is a littlefaster with certain drugs.
Um but by and large, by thetime you see that person back.
(29:59):
In two or four weeks, uh, theyshould be significantly more
comfortable.
Erich Schramm, MD (30:04):
Wow.
Michael Bernhardt, MD (30:04):
And I typically give a drug about two,
three months.
And if they really haven'tturned around, then we start
talking about changing.
Okay.
Unless they just, you know, getobviously worse.
Erich Schramm, MD (30:16):
You know.
Um great.
So uh that's actually prettyimpressive that we can take, and
I've seen some really, reallychallenging cases with people
with atopic dermatitis,especially those kids.
And you know, it is a reallychallenging quality of life, and
you know, you see those thosepatients plenty, and to think
that in a matter of months thatyou can see such a such an
(30:39):
amazing turnaround.
Michael Bernhardt, MD (30:40):
Weeks,
Erich Schramm, MD (30:41):
right?
Michael Bernhardt, MD (30:41):
Weeks,
Erich Schramm, MD (30:41):
right?
Yeah.
And um, you know, we we joke uhto say that you know, we talk
about the three-headed monsterin dermatology, which were uh
atopic dermatitis,hidradenitis suppurativa, and
psoriasis.
And uh, you know, you're makingthat comment you'd said earlier
that you know, here we had whatdid you say, institutionalized
(31:02):
mediocrity for treatments upuntil a time that we ended up
and you know these kind ofgame-changing therapies came
out.
Michael Bernhardt, MD (31:10):
And yeah, these are these are true game
changers.
I mean, it's nice to have drugsthat deliver on the promise,
and that really work.
They've been approved by theFDA after very rigorous, like
studies that we did here.
We were involved in the phasetwo for dupilumab, right?
Very rigorous clinical trials,multi, you know, multiple
(31:31):
randomized clinical trials, hugedata sets with huge patient
populations that are by andlarge safe and effective.
Erich Schramm, MD (31:39):
Right.
Michael Bernhardt, MD (31:40):
You know, it's a whole different world
than even 15 years ago.
Erich Schramm, MD (31:44):
Right.
Right.
Michael Bernhardt, MD (31:45):
In my day, when I first came out with
someone with bad atopicdermatitis, we'd immediately
just start on one of theinjectables, one of the orals.
You know, in those days it wastap water wet dressings with
topical steroids, keep it onovernight, maybe some
phototherapy, yada yada yada.
And if you're better if youwere lucky, they were at best
twenty, thirty, forty percentbetter, which was you know not
(32:08):
where we want to be.
Erich Schramm, MD (32:09):
Wow.
So and that leads now uh to agreat improved job uh you know,
uh job satisfaction as adermatologist.
Michael Bernhardt, MD (32:18):
Thanks to clinical research.
Right.
All this is thanks to clinicalresearch.
Erich Schramm, MD (32:21):
Well, again, I appreciate your efforts and uh
every Friday an opportunity tobe able to learn from uh such a
great educator and clinician asyourself, so always appreciate
that.
Thank you.
So I understand the fourthheaded monster is gonna be
alopecia, right?
Yeah, so we're gonna be uhjumping, doing a deep dive uh at
(32:44):
an op uh in our next podcasttalking about alopecia.
Michael Bernhardt, MD (32:47):
We haven't talked about restaurants
yet.
Erich Schramm, MD (32:49):
Ah okay, all righty.
Okay, you go first.
Michael Bernhardt, MD (32:53):
Okay.
well, I would you know, I wasin Mayo Hospital for about five
days with a knee problem, and Ifound that of all the hospitals
I've been in, their food'sreally pretty good.
Um I'm not telling people it'sthe Mayo clinic.
I'm not telling people to goget sick just so that they can
get their food to say it out.
(33:14):
But my wife loved the food atat Mayo Hospital.
Erich Schramm, MD (33:18):
Um did they have a wine pairing with that?
But how did that work?
Michael Bernhardt, MD (33:21):
I don't think so.
But all kidding aside, um theonly new place that we've gone
that's been really pretty goodis uh is in St.
Augustine, Andaman.
Okay, what's that?
It's uh Asian.
Oh Asian Fusion, and um we'vegone there three or four times,
and the food's always beenreliably great.
Erich Schramm, MD (33:38):
Okay.
Well I'll have to look that up.
So my go-to now, um so I likeSouth Indian cuisine.
And so I would direct peopleto the Honest South Indian
restaurant that's over there onBay Meadows.
It's not very, it's not a fancyplace.
Michael Bernhardt, MD (33:59):
It's called Honest South Indians.
Erich Schramm, MD (34:01):
Honest, huh?
You know it's gotta be good,right?
Honestly
Michael Bernhardt, MD (34:04):
Honestly,
yeah.
So but yeah, so if you want toget a real sense for true,
authentic, delicious SouthIndian food, that's that's the
place to get.
My wife and kids love it, we'regonna go there.
Erich Schramm, MD (34:17):
Yeah.
It can get hot and be warnedit can be hot and spicy.
Michael Bernh (34:21):
I'll tell them to keep it in the negative range.
Cool, man.
Erich Schramm, MD (34:24):
Cool.
Anything else uh you want toput out there?
Michael Bernhardt, MD (34:27):
I think we've covered pretty much
everything you can cover.
Erich Schramm, MD (34:30):
We used all the big words that could
possibly come to mind on
Michael Bernhardt, MD (34:33):
a lot of syllables for a
Friday afternoon.
Erich Schramm, MD (34:35):
Maybe we've got to look up some things too
to make sure we're we're ontrack.
But thanks again, Mike.
It's always such a pleasure towork with you.
Mi (34:41):
My pleasure too man, enjoyed it.
Erich Schramm, MD (34:42):
We'll see you.
Announcement (34:43):
Thanks for joining the MedEvidence Podcast.
To learn more, head over toMedevidence.com or subscribe to
our podcast on your favoritepodcast platform.
Welcome to MedEvidence, where we help you
navigate the truth behindmedical research with unbiased,
evidence-proven facts, hosted bycardiologist and top medical
researcher, Dr.
Michael Koren.
Erich Schramm, MD (00:11):
Hello, and welcome back to another episode
of the MedEvidence Podcast.
I'm your host, Dr.
Erich Schramm.
I'm a board-certified familyphysician and longtime clinical
research investigator with theENCORE Clinical Research Group.
And I'm very excited to besitting across the table again
from one of my favoritedermatologists and esteemed
clinical research colleagues,Dr.
(00:31):
Michael Bernhardt.
Welcome back to another episodeof the MedEvidence Podcast.
Michael Bernhardt, MD (00:36):
Great to be back.
It's been a little while.
Erich Schramm, MD (00:38):
Yeah, it has been.
So just getting caught up onthings.
We've done a couple of few ofthese before.
Michael Bernhardt, MD (00:44):
Right.
Erich Schramm, MD (00:45):
And remember the kind of the origin story
for this was, you know, onFridays, we have opportunity to
work together, collaborating onpatients and studies.
And it came out of that that,you know, we spent a lot of time
discussing, you know, topics,clinical research reports, and
(01:06):
all the things that are comingdown the pike.
And people realized that, youknow, we'd get into very
detailed descriptions anddiscussions about, you know,
disease pathways, and it wasvery educational.
And they said, hey, you know,you guys should go and do a
podcast because you know, wejust we just like hanging out,
two docs, talking about, youknow, research and talking
(01:29):
about our patients.
And sure enough, and I lookedat Mike and I said, gee, Mike,
we should do some podcasts.
And I said, Well, how manypodcasts had you done at that
time?
And I believe your answer was
I think I had a my grand totalwas um zero.
Right, it was zero, somewhere between zero
and one.
And then the question was zero,right?
How many podcasts I'd actuallyhosted?
(01:50):
And the answer was for me a bigzero.
And so based on that kind ofexperience, we thought it would
be a great idea to plungeforward and do these kind of
podcast series.
And I'm, you know, I'm kind ofsaying that in a facetious way,
but quite honestly, you know,you really have a, you know,
you're not just a dedicatedclinician, but you're a clinical
(02:11):
researcher, an educator.
And so, you know, you when youcome into the office, um, I feel
like you really do bring a lotto the staff, including myself,
but also to the patients.
You know, you really do havequite a very holistic view of
patient care, and so I reallyreally admire and respect that.
Michael Bernhardt, MD (02:32):
As do you.
Erich Schramm, MD (02:33):
There you go.
Michael Bernhardt, MD (02:34):
Right back at you.
Erich Schramm, MD (02:34):
Right back at you.
Back at you, buddy.
So today we're gonna be talkingabout atopic dermatitis.
And, as you like to do withthese talks, you always do a
great job, kind of foundational,explaining a good definition
for atopic dermatitis, and thenmaybe running through, you know,
the epidemiology, etiology,and then you know, maybe even go
(02:56):
back and forth on a fewdifferent things.
Michael Bernhardt, MD (02:57):
Sounds good.
So we've come a long way withatopic dermatitis, and and
honestly, thanks to clinicalresearch, you know, and and you
know, it's so popular to bashthe pharmaceutical companies.
But like I tell the residents,you could be the best carpenter
in the world, but if you don'thave a hammer, nails, a skill
saw, and a level, you're notgonna be able to do anything.
(03:20):
And without the companiesactually make the drugs that we
can use, you know, we're back inthe Stone Age.
So we've had a lot of reallygreat progress with Atopic in
about the last eight or tenyears.
You know, they've drilled downand kind of found some very
significant pathways that drivethe disease condition.
(03:42):
You know, Atopic is known,quote unquote, as the itch that
rashes, right?
I think that's from thetextbooks around back when when
I had a full head of hair.
And I think our next talk'sgonna be about hair loss.
Erich Schramm, MD (03:56):
It's gonna be a hair loss.
I mean, you know, it's reallyinteresting.
You that's that's the phrasethat comes to mind because I was
one of your residents at onetime, and that was one of those
clinical pearls that stuck in myhead and found it very helpful,
you know, throughoutthroughout my career.
So I that's the great greatpearl, right?
Michael Bernhardt, MD (04:11):
Yeah, a lot of times each will precede,
you know, what you can see andwhat you can feel.
Um and it's common, starts inkids, very common in kids.
Usually in the young kids, sixmonths or so, periorificial, you
know, around the mouth, and andthen it spreads to the
anticubital folds, you know, thebends of the elbows, the bends
of the knees.
And these kids can be prettymiserable.
They really can be miserable,and it makes the whole family
(04:33):
miserable.
And you know, back in the day,all we had was topical steroids
and moisturizers andantihistamines.
And and the thing is,antihistamines are only
marginally ineffective in thiskind of itch because a lot there
are other itch pathways betweenthe skin and the brain, you
know, via the spinal cord thatgo through mechanisms other than
(04:56):
histamine.
You know, gavinergic pathways,what they call the cowhage
pathway.
And and we found that a lot ofthese cytokines or these
cycling intermediaries that helpstart the fire that that
transmits itch to the brain, aretotally independent of
histamine.
Right?
So we have molecules likeinterleukin 31, which is a
(05:19):
primary pruritogen of the skin,molecules like interleukin 4 and
interleukin 13, which drive thewhole inflammatory cascade.
And now they're they'restarting to drill a little
deeper and they're looking atother molecules like one of the
studies that we're trying toget, which is a combination of
blocking interleukin 4 andblocking another molecule called
TSLP.
(05:39):
And I always, always, alwaysmutilate the real name of this
thing, you know.
So I I'm just gonna stick withTSLP.
It's like FOMBO, strombo,fymbic, strombic, lymphopuetin,
or something like that.
That's right.
Erich Schramm, MD (05:52):
Sound sounds like a little bit this afternoon
we're gonna sit down and
Michael Bernhardt, MD (05:56):
I've tried to study it a hundred
times.
I still mutilate that.
But TSLP, IL-25, and IL-33 arewhat are called uh alarmins,
A-L-A-R-M-I-N-S.
And alarmins are these littlecytokine fragments that are
released with any kind ofirritation to the epidermis.
Right.
And they act like as the alarmclock.
That's why they call themalarmins, and tell the rest of
(06:18):
the inflammatory cascade, hey,wake up, there's something going
on here that doesn't belong,and it triggers the whole itch
scratch cycle.
So uh right now we have greatdrugs that are FDA approved down
to age six months of age.
For example, a drug likedipolumimab, FDA approved down
to six months of age.
It's an injectable and itworks great at shutting the
(06:41):
process off.
Erich Schramm, MD (06:42):
That's IL-4 & IL-13.
Michael Bernhardt, MD (06:44):
It blocks IL-4 & IL-13.
Erich Schramm, MD (06:46):
Right.
And then the 13 inhibitors, Ithink, are are only FDA approved
down to I have to check and seewhether it's 12 or or whether
it's approved for adolescents orjust adults.
I don't not sure off the top ofmy head.
The 13 inhibitors are alsoavailable.
And then there's a new class ofdrugs for atopic dermatitis
called JAK or JAK inhibitors.
(07:08):
And those are orals.
So in those kids and youngadults who are the ones who
predominantly have this whocan't tolerate an injection,
there's an oral form, but theyou know, there's risk to
benefits, and they all have thisside effect risk.
How do you think in terms ofwhen you're grading severity,
mild, moderate, severe, youknow, do you have some distinct
(07:31):
parameters that you're lookingin that and helping you to
decide what kind of therapiesyou're going to be looking at
with a patient?
Michael Bernhardt, MD (07:37):
And and the way when I'm teaching, when
I'm teaching residents, I alwaystell them that you know a lot
of there's no definitivediagnostic test for atopic
dermatitis.
You do a skin biopsy, it showsinflammation, what they call
spongiosis, which is microfluidin the epidermis.
Um maybe you'll see someeosinophils, which are cells
(07:57):
that get upregulated whenthere's an allergic process.
You can do some blood tests,may help, may not help.
The one I use as a yardstick isIgE.
Yeah.
Right?
And IgE is helpful if it'selevated.
If it's normal, it doesn'treally help you.
And people have to rememberthere's two pathways.
There's an allergic pathway andthere's an auto-inflammatory
pathway that's autonomous fromallergy.
(08:19):
So there's no real diagnostictest.
It's a clinical conundrum.
And you know, you look at theperson, you see, uh, you know,
are you itching?
Well, if someone's sittingthere scratching themselves to
death, it's kind of a sillyquestion to ask.
But you ask, how bad is theitch?
And criteria for itching is ifthe itch is such that it
(08:39):
prevents the person fromsleeping at night or staying
asleep at night, that's severe.
Erich Schramm, MD (08:44):
Right.
Michael Bernhardt, MD (08:44):
That's severe disease.
Um if it's in an in a kid oryoung adult, if it's impairing
their ability to stay awake andfunction in school, um, if they
can't go with their peers, ifthey're soccer players, they
can't play soccer.
A lot of times this is comorbidwith asthma, so they start
running around, they getbronchospasm.
Um, that's severe.
Right.
All right.
Uh kid's a basketball playerand he can't lift his arm ups to
(09:06):
shoot because his the hisaxillary area is so torn up that
it rips his skin when he triesto shoot a basketball.
Well, that's severe disease.
And, you know, back in the daywith these people, all we had
was topical steroids andantihistamines.
And you know, more often thannot, they did not accomplish the
full task that we wanted tohave done.
Erich Schramm, MD (09:27):
Right.
So, um, and just maybe we cantalk a little bit about how
important it is in terms of skincare and for these patients and
um moisturizers and you know, Imean what what kind of soaps uh
they should use or avoid.
Uh maybe you talk about that.
Michael Bernhardt, MD (09:43):
So the to to get to that answer, you have
to uh visualize the skin aslike a five-layer cake, right?
Think of the epidermis as afive-layer cake.
The basement, the first layeris the basal cells, right?
The basement layer, basalcells.
And the um the next layer isthe squamous cells, then there's
the spinous cells, and it's thegranular cells.
(10:04):
And then on top of the cake,like a thick layer of saran
wrap, you have the the stratumcorneum, which is the outer
barrier.
Right.
Right.
So we always say in in atopicdermatitis as a disrupted
barrier.
And when you think about thatand try to take it out of a
nebulous concept to a concreteconcept, what is disruptive?
Well, you you look at thegranular layer.
(10:26):
The granular layer is calledthe granular layer because, and
this is going to come as a shockto people out there, the cells
have granules in them, right?
Erich Schramm, MD (10:33):
Right.
Michael Bernhardt, MD (10:34):
So everybody recovers.
Erich Schramm, MD (10:35):
Right.
Michael Bernhardt, MD (10:35):
So these cells have granules.
And the problem in the atopicworld is that these granules,
which are important forsecreting uh filaggrin, which is
a structural protein uh for thestratum corneum, and it also
helps with junctional and tyingthe junction, the skin cells
together, or they call itjunctional adherence.
Um and then there's what'scalled the odland bodies, which
(10:57):
secrete um cholesterol andsterols and free fatty acids,
which are like the intercellularcement substance, right?
So when these granular, and weknow that in atopic dermatitis,
these granular cells aredefective.
Uh either A, they're secretingdefective products, um, and or
B, they don't secrete at all,they get jammed up.
(11:20):
Okay.
And when you're not secretingthese sterols or or uh what
they're called ceramides, theskin has a gap.
Normal ceramides run abouttwenty to twenty-four carbon
chains in length.
So think of it as like, I don'tknow, uh a tire chain that has
(11:40):
a certain length.
All right.
Okay.
So for the tire chain tofunction, it's gotta have X
amount of loops to it.
So in atopic dermatitis, it'slike X minus 10 in these loops.
Erich Schramm, MD (11:51):
So these are these are inherent to good skin
health because it maintains theintegrity of the skin in itself.
Michael Bernhardt, MD (11:58):
And even more importantly, sometimes when
these tire chains come out tooshort, they can actually act as
an inflammatory driver and uhand aggravate the situation.
So that's what leads to thisdefective barrier.
So moisturizing is superimportant.
And the reason I always tell mypatients to get a moisturizer
with ceramides is because ifthese kids and young adults are
(12:21):
not producing ceramides in sucha way that they keep the barrier
whole, you need to supplementthat.
So a moisturizer withoutceramides is only kind of
quasi-effective.
Erich Schramm, MD (12:33):
Is that you know if uh if I go to the
pharmacy and I find this easy tofind uh moisturizers with
ceramides, or do I have to lookon the backside and
Michael Bernhardt, MD (12:43):
now they they advertise it because every
you know everybody's kind of hipto the need for ceramides.
Erich Schramm, MD (12:48):
Okay.
So uh that's critical tomaintain um good skin health,
um, moisturizing.
Uh what about soaps?
Michael Bernhardt, MD (12:58):
Uh try to keep them bland.
You know, I'm I'm a big fan ofwhite fragrance-free dove soap.
Okay.
It's got mineral oil in it,which is lubricating.
Um, I'm not really a big fan ofof any fancy soaps that have
fragrance or color or dyesbecause people with atopic
diathesis are more sensitiveanyway.
So things that normallywouldn't irritate you or me or
(13:20):
or you guys in the room, youknow, if you have atopic, it
might set you off.
Right.
So try to keep it kind of onthe bland side.
On the mild side, not the wildside.
Erich Schramm, MD (13:30):
Uh uh shower uh cool or warm?
Michael Bernhardt, MD (13:34):
What any that means so if you take a
shower that's too hot, it'sgonna stimulate those itch
fibers and trigger that wholeitch scratch response.
So try to keep it moderate.
I know on a cold winter day youlove to crank that hot shower
up.
We all do.
And it does.
It feels so good, but if youhave atopic dermatitis, it's
gonna set you off.
Erich Schramm, MD (13:52):
Okay.
Uh good, good food for thought.
Um, the other question that'scoming to mind is um, can can
you describe the like earlyversus late stage disease
processes?
Because you know, at some pointthat you haven't activated so
much of that uh theauto-inflammatory or the the
(14:15):
allergy arm of it, but it itdoes ramp up over a period of
time, right?
Michael Bernhardt, MD (14:19):
Yeah, it's kind of cool because it's a
it's kind of a multiphasedisease, right?
And we know that in the firstphase it's inflammatory, and
then it becomes quote unquotefibrotic.
In other words, the skinthickens up.
And the TH2, you know, there'stwo inflammatory pathways,
right?
At least, I'll say three.
Erich Schramm, MD (14:36):
Yeah, please remind me of those.
So now we've talked about them.
Michael Bernhardt, MD (14:39):
And I'm sure there's going to be a
zillion more, you know, by thetime you guys are my current
age, there'll be a zillion morepathways found out.
But I mean, right now the threemain highways that we look at
is TH17, TH1, TH2.
And remember, there's someplasticity between the TH1 and
the TH2 pathway.
Um so with atopic dermatitis,we're mostly talking about the
TH2 pathway.
(15:00):
And what we find is that one ofthe little interesting things
that we see in some of these TH2diseases, they do end with
thickening or fibrosis of theskin.
Um we know that we're not sureof what what the exact mechanism
of that is, but we know that inpeople with chronic atopic
dermatitis, the skin will whatwe call licinofire, thicken.
(15:21):
Right.
Um now what's interesting isthere is a newer biologic drug,
nemolizumab, which doesn'tblock interleukin-4 or 13, which
are the main drugs that we'vebeen using.
It blocks interleukin-31.
Interleukin-31 is what's calleda pruritogen.
In English, to take it out ofscientific ease and put it in
(15:41):
English, pruritogen meanssomething that makes you itch.
Okay.
Okay.
So interleukin-31 is one of these
primary pruritogens that reallycauses severe itching.
It shares a receptor.
So in other words, when thesecytokines, if you think of
cytokines as a key, right?
They're floating around in yourbody, they're keys.
They're looking for a littlelock to go into in turn, right?
(16:05):
So interleukin-31, that littlekey is looking for its
receptor or its lock.
Well, it shares a receptor withanother molecule.
This is pretty cool.
Called Oncostatin M, which isOncostatin M is a cytokine that
or a receptor site that drivesfibrosis.
It also has other you knowoncologic related properties
(16:28):
that are just kind of beingdiscovered that are not germane
to this talk.
Um but what it what it does isit does stimulate fibrosis.
Erich Schramm, MD (16:36):
At the level of
the receptor level.
At the receptor level.
Michael Bernhardt, MD (16:40):
So that may be one of the you know,
activating IL-31 and oncostatinM may be one of the reasons that
tickles that pathway offibrosis.
So these the couple of thesedrugs have been um FDA approved
not just for atopic dermatitis,but another inflammatory
fibrosing disease calledprurigo nodularis, where people
get these horribly itchythumbtip size lumps on their on
(17:03):
their trunk and on their arm ontheir extremities.
And both these drugs work likea charm in terms of reducing not
just the inflammation, but thethickening and the fibrosis.
Erich Schramm, MD (17:13):
Once a person, say they develop some of
those thicker plaques um thatyou sometimes see, um, is that
reversible?
Can you how do you approachthat?
Michael Bernhardt, MD (17:24):
With one of these injectables, either
with um the 413 or the 13inhibitors or the the 31 OSM
inhibitor.
And that allows the skin tokind of re-engage and restore
kind of a more normal.
You're taking the inflammatory onus
away, and it with time itnormalizes.
Now, thicker fibrotic skintakes more time to normalize
(17:46):
than just quote unquote itchyskin.
With most of these drugs, theitching is gone within a day or
two.
Right.
And that's the main thing.
Because if you're itching, it'snever going to go away, right?
If you if you continue toitchy.
Yeah, the itch relief is a godsend.
You know, we're even seeing itnow with some of the topicals,
the topical JAK inhibitors, youknow, ruxolitinib, and there's a
new one that has some sort ofname that I can't ever remember,
(18:07):
um, "enzupco" or somethinglike that.
But they're topical JAKinhibitors.
And they they're they're greatfor chronic eczema, they're
great for chronic atopicdermatitis.
Um we use ruxolitinib, topicalruxolitinib for um vitiligo.
They stop itch in a matter ofhours.
I mean hours.
They've done studies wherethey've charted it in 15-minute
intervals, and you know, the theuh it's an inverted parabola
(18:31):
and how quickly they respond.
Wow.
Yeah,and we're using a lot of
multisyllable words too.
Erich Schramm, MD (18:36):
No, I get that.
You're must be Friday.
It is.
Well, we like that.
Um and we've done uh and we'redoing studies on ruxolitinib for
hidradenitis suppurativa, bythe way, which was another uh uh
great podcast with you.
So um, and we talked um in thepast, we talked a little bit
about um you've done some reallygood definitions to talk about
(18:57):
um the JAK-STAT pathways um anduh really some great uh ideas
some about understanding uminhibiting all the different
types of inflammatory cytokinesthat that were found in these
JAK inhibitors.
And um and just so that whenyou I think when we left off on
that, that we uh, or at leastyou were saying that that
(19:19):
there's a very high comfortlevel to be using, especially a
topical JAK inhibitor likeruxolitinib, um, we didn't have
any really safety concerns withit.
We thought it was or thought itwas a very safe and effective
treatment.
Um, but you know, you have todo the studies, right?
Yes, you can't.
Michael Bernhardt, MD (19:37):
I mean, all these drugs are are you
know, all drugs have sideeffects.
And when I'm doing talks, Ialways tell people that you
can't skip over important safetyinformation because A, it's
important, B, it's safety, andC, it's information.
Erich Schramm, MD (19:51):
Right,
Michael Bernhardt, MD (19:52):
Right.
So you always have to go overthat.
And and you know as aclinician, you'll see some
regulatory things that sometimesmake sense.
Um but again, as a clinician,you don't always see the whole
regulatory picture.
Right.
So FDA has the same warningsfor the topical ruxolitinib in
terms of of you knowcardiovascular events, D V T,
(20:15):
PE, thromboembolic phenomenathat they do with some of the
oral JAKs.
Um so far there's not aplethora of literature that
really um endorses that.
And you know, I don't again,I'm only seeing it from a
clinician viewpoint, not from aregulatory viewpoint.
But I still um counsel patientsas to the risks, including DVT,
(20:39):
uh deep vein thrombosis,pulmonary embolism, even from
the topical.
Erich Schramm, MD (20:43):
No.
Right.
Um Well, you have to, right,and that's a sign of a good
idea.
I think full disclosure forthose patients.
Michael Bernhardt, MD (20:52):
So the easiest way to think about the
JAKs if you want to kind of putthe JAK-STAT pathway in
perspective compared to blockingthe cytokines.
Erich Schramm, MD (20:59):
Right, which we've talked about before.
Michael Bernhardt, MD (21:01):
But the cytokines is like you're putting
the key in the ignition.
Okay?
If you don't have the rightkey, you can't turn on your
ignition.
Um the JAK-STAT pathway is thatelectrical conduit from the
ignition to the starter of yourcar.
Okay.
All right, and that's the easiest
way to think about it.
Erich Schramm, MD (21:15):
Okay, I like that.
Uh-huh.
Now, so um to that point, andthinking about um the four and
thirteen inhibitors, now we got31 inhibitor.
Um, do you see that see that asbeing a potentially greater
benefit than for the four andthirteen, or is there enough
(21:35):
information out there to to cometo some conclusion about it?
Michael Bernhardt, MD (21:38):
You know, they're all great drugs, right?
And you prioritize based onpatient age and in terms of
what's appropriate for thepatient.
And the comorbidities.
Um, you know, everybody'safraid of these JAK inhibitors,
but there was a study publishedMay, Journal of Clinical
Allergy, that looked atabrocitinib, which is there's
(21:58):
two main JAK inhibitors,pacritinib and abrocitinib, both
great drugs.
They both have done absolutewonders for people.
But this particular study justfocused on abrocitinib.
And they were saying that inthe low dose, the 100 milligram
dose, the risk of cardiovascularand thromboembolic phenomena
were no different in a youngerpopulation, the population under
65, um, which at that age to meis still a younger population.
(22:22):
But in the under 65 population,there was no difference between
the SEER data, the expectedepidemiologic data.
When patients are over 65, thenthe risks start to trend up a
little bit.
Right.
And when you have to go on the higher
dose, the 200 milligram dose,the risks start to trend up a
little bit.
But for younger people on thelow dose, um, based on this
(22:44):
article, the data shows thatthat the morbidity is about
equivalent to what you'd expectin the population.
Erich Schramm, MD (22:50):
Was that, to remind me, was that a kind of a
pan-JAK inhibitor, or is that amore selective JAK inhibitor?
Michael Bernhardt, (22:58):
abrocitinib is more of a selective JAK-1.
I mean, all these you know, allthe drugs have some effect on
multiple JAK sites, but you youlook at how effect how much
upregulation of the other JAKsand the difference between the
JAK 1 and JAK2 upregulation ishuge to the point where it's
really just a selective JAK 1.
Erich Schramm, MD (23:16):
Right.
And maybe, and just remind usum, you know, what are some of
the the bad actor um cytokinesthat are downstream once JAK 1
is is out of the same.
Michael Bernhardt, MD (23:27):
Yeah, I mean so so all these things
you're looking at like ininterleukin 6, TNF Alpha,
Interferon-gamma, uh those thosethere's others, but I mean
bottom line is those guys drivea lot of the inflammatory
cascade.
Great.
So now we've got um so we'vegot uh a number of tools in the
armament for atopic dermatitiswith some uh really solid
(23:51):
approaches with monoclonalantibodies.
We've got oral JAK inhibitors
There was a meta-analysis lastyear that where they looked at
at a upadacitinib.
I think they did 45 studies,15,000 patients, and they found
basically the same thing that inlow dose, the risk, the
cardiovascular and the DVT PErisk was equivalent to what
(24:12):
you'd see in the SEER data.
Right.
And that, you know, when you bump up the
dose, yeah, there's acorresponding increase in risk.
But low dose in a youngerpatient population, you were
pretty much at SEER data level.
Erich Schramm, MD (24:24):
Another uh question that comes to mind, and
um getting back and talkingabout some of the other topicals
out there, maybe you could talkabout the
calcineurin inhibitors and someof the other, you know, uh you
know, we've used andpimecrolimus and some of these
other things.
And if there's were their placefor those
Michael Bernhardt, MD (24:42):
So they're great drugs and they
work and and they're they're anice alternative to topical
steroids.
Um, you know, you you can'tparticularly in young kids,
because young kids have a highsurface to volume ratio.
So if you saturate their skinwith too strong a steroid, you
can get some systemic effects.
Right.
You know, you can get someadrenal cortical suppression.
(25:02):
Um, that's a lot ofmultisyllable words on a Friday
afternoon.
Anyway, you can get someadrenocortical suppression if
you're just bathing the kid inin a mid or higher potency
topical steroid multiple times aday.
Right.
Um so I mean a short blast ifyou need to bulldoze through it
is fine, but if you can switchthem off of that and get the
equivalent of steroid sparinglike we do with orals, with the
(25:25):
topical calcinerium inhibitors,ELIDEL, which is pimecrolimus,
and Protopic, which is uhtacrolimus, you can get pretty
much the same mileage withoutthat steroid risk.
Erich Schramm, MD (25:36):
Right.
And so for the the parents thatare out there listening and
they're like, wow, well, how doyou know uh how much uh topical
steroid is too much or which isyou know what's the right or the
wrong uh topical steroid outthere, I'd say, well, talk to
your informed dermatologist tomake sure that you know if
there's really you know concernsabout that.
So that's that's a that's agood point.
(25:58):
So uh we have a lot of optionsout there um aside from topical
steroids, but like you said,they're always available there
if you need it.
So um we've talked about uhways to keep the skin healthy
and having good skin hygiene.
Uh you've given us some reallygood uh background and talking
about and understanding the uhthe uh interleukin inhibitors,
(26:21):
the monoclonal antibodies.
We talked about um the uh howthe JAK-STAT inhibitors um are
out there and really being avery effective uh element.
Um fantastic.
Anything else that might be outyou see coming down the pike?
Michael Bernhardt, MD (26:37):
You know, we use sometimes left people
take bleach baths, which meansyou take a bathtub full of water
just like you normally wouldand put a cap, maybe two caps,
not a cup, not a C U P, a C A P,a cap or two of bleach.
And the you know, when I tellpeople that they look at me like
I'm either crazy or I have athird eye.
Erich Schramm, MD (26:54):
I've been looking around.
I'm uh maybe there is a thirdeye that is that is a first,
right?
Michael Bernhardt, MD (27:00):
Um and then I always say, well, there's
a reason for it.
And you know, why do we putchlorine, which is bleach, why
do you put it in swimming pools?
Because it kills bacteria.
Erich Schramm, MD (27:09):
Right.
Michael Bernhardt, MD (27:09):
Right?
So on the micro level, if youtake a bleach bath once every
week or two, you're gonna killthat staph that's on the skin.
You know, like I was talkingabout before with the uh
defective granular layersecretions, right?
Normally the skin secreteswhat's called antimicrobial
peptides, which reduce staphflora, and they do things to
make it harder for the staphaureus, which is the main uh
(27:32):
infection driver, to bind toskin.
Well, in kids with atopicdermatitis with defective
granular secretions, not only dothey not have enough
antimicrobial peptides to wardstaph off, they actually have
receptors on their stratumcorneum that encourage staph
binding.
So these kids are more prone tostaph carriage.
Now, when you when you use ableach bath once every week or
(27:55):
two, you're killing thatorganism off in a way that does
not cause drug resistance.
Okay.
And you're not going to put thekid at risk for a cap of bleach
in the tub units.
But um the other point I wasgoing to make is that once you
repair the barrier, when you'reusing the 413 or the 13
inhibitors or the JAKinhibitors, and you repair the
barrier, particularly in thefourth, there's data that shows
(28:16):
that with the 413 inhibitors,um, you actually reduce the
kid's risk of infection becauseyou've reintegrated the barrier.
Erich Schramm, MD (28:23):
Right.
Do you ever see a time whereyou would put somebody on just
oral antibiotics or any kind ofprophylactic or any time, uh any
time if you would consider anycourses for oral antibiotics in
that?
Michael Bernhardt, MD (28:37):
Yeah, when they're if they're starting
to look impetenized, yeah,sure.
Okay.
Sure, sure.
But I would definitely like tosee them do a bleach bath.
And then the other thing toremember, moms and dads out
there, especially if any of youwork with cement, right?
The skin, when you're in ashower or bath, is like wet
cement.
And when you get out of thatshower and bath, you've got
about four or five minutesbefore that cement sets.
(28:59):
And once the skin sets, it'sless effective with the
moisturizers.
So when you get the child,yourself or your child out of
the shower, pat dry, and thenthat's the time to put your
moisturizer right on.
Don't wait 20 or 30 minutes,put it on right after you get
out, and you get a betterresult.
Erich Schramm, MD (29:16):
Wow.
That's that's great.
I mean, that's just greatgeneral, good skin care.
Um back to thinking about umthe JAK inhibitors and the
monoclonal antibodies.
Um, as far as um expectationsfor patients for healing, their
timelines.
Is there one that's a littlequicker than the other, or is it
(29:36):
all about the same?
Michael Bernhardt, MD (29:38):
They're all pretty good.
Uh they're all pretty good.
When you look at the studies,there's a lot of overlapping
data with the low dose JAKsversus the 413 inhibitors.
They're really pretty good.
Um, some studies, some of thedrugs have studies that show
that itch reduction is a littlefaster with certain drugs.
Um but by and large, by thetime you see that person back.
(29:59):
In two or four weeks, uh, theyshould be significantly more
comfortable.
Erich Schramm, MD (30:04):
Wow.
Michael Bernhardt, MD (30:04):
And I typically give a drug about two,
three months.
And if they really haven'tturned around, then we start
talking about changing.
Okay.
Unless they just, you know, getobviously worse.
Erich Schramm, MD (30:16):
You know.
Um great.
So uh that's actually prettyimpressive that we can take, and
I've seen some really, reallychallenging cases with people
with atopic dermatitis,especially those kids.
And you know, it is a reallychallenging quality of life, and
you know, you see those thosepatients plenty, and to think
that in a matter of months thatyou can see such a such an
(30:39):
amazing turnaround.
Michael Bernhardt, MD (30:40):
Weeks,
Erich Schramm, MD (30:41):
right?
Michael Bernhardt, MD (30:41):
Weeks,
Erich Schramm, MD (30:41):
right?
Yeah.
And um, you know, we we joke uhto say that you know, we talk
about the three-headed monsterin dermatology, which were uh
atopic dermatitis,hidradenitis suppurativa, and
psoriasis.
And uh, you know, you're makingthat comment you'd said earlier
that you know, here we had whatdid you say, institutionalized
(31:02):
mediocrity for treatments upuntil a time that we ended up
and you know these kind ofgame-changing therapies came
out.
Michael Bernhardt, MD (31:10):
And yeah, these are these are true game
changers.
I mean, it's nice to have drugsthat deliver on the promise,
and that really work.
They've been approved by theFDA after very rigorous, like
studies that we did here.
We were involved in the phasetwo for dupilumab, right?
Very rigorous clinical trials,multi, you know, multiple
(31:31):
randomized clinical trials, hugedata sets with huge patient
populations that are by andlarge safe and effective.
Erich Schramm, MD (31:39):
Right.
Michael Bernhardt, MD (31:40):
You know, it's a whole different world
than even 15 years ago.
Erich Schramm, MD (31:44):
Right.
Right.
Michael Bernhardt, MD (31:45):
In my day, when I first came out with
someone with bad atopicdermatitis, we'd immediately
just start on one of theinjectables, one of the orals.
You know, in those days it wastap water wet dressings with
topical steroids, keep it onovernight, maybe some
phototherapy, yada yada yada.
And if you're better if youwere lucky, they were at best
twenty, thirty, forty percentbetter, which was you know not
(32:08):
where we want to be.
Erich Schramm, MD (32:09):
Wow.
So and that leads now uh to agreat improved job uh you know,
uh job satisfaction as adermatologist.
Michael Bernhardt, MD (32:18):
Thanks to clinical research.
Right.
All this is thanks to clinicalresearch.
Erich Schramm, MD (32:21):
Well, again, I appreciate your efforts and uh
every Friday an opportunity tobe able to learn from uh such a
great educator and clinician asyourself, so always appreciate
that.
Thank you.
So I understand the fourthheaded monster is gonna be
alopecia, right?
Yeah, so we're gonna be uhjumping, doing a deep dive uh at
(32:44):
an op uh in our next podcasttalking about alopecia.
Michael Bernhardt, MD (32:47):
We haven't talked about restaurants
yet.
Erich Schramm, MD (32:49):
Ah okay, all righty.
Okay, you go first.
Michael Bernhardt, MD (32:53):
Okay.
well, I would you know, I wasin Mayo Hospital for about five
days with a knee problem, and Ifound that of all the hospitals
I've been in, their food'sreally pretty good.
Um I'm not telling people it'sthe Mayo clinic.
I'm not telling people to goget sick just so that they can
get their food to say it out.
(33:14):
But my wife loved the food atat Mayo Hospital.
Erich Schramm, MD (33:18):
Um did they have a wine pairing with that?
But how did that work?
Michael Bernhardt, MD (33:21):
I don't think so.
But all kidding aside, um theonly new place that we've gone
that's been really pretty goodis uh is in St.
Augustine, Andaman.
Okay, what's that?
It's uh Asian.
Oh Asian Fusion, and um we'vegone there three or four times,
and the food's always beenreliably great.
Erich Schramm, MD (33:38):
Okay.
Well I'll have to look that up.
So my go-to now, um so I likeSouth Indian cuisine.
And so I would direct peopleto the Honest South Indian
restaurant that's over there onBay Meadows.
It's not very, it's not a fancyplace.
Michael Bernhardt, MD (33:59):
It's called Honest South Indians.
Erich Schramm, MD (34:01):
Honest, huh?
You know it's gotta be good,right?
Honestly
Michael Bernhardt, MD (34:04):
Honestly,
yeah.
So but yeah, so if you want toget a real sense for true,
authentic, delicious SouthIndian food, that's that's the
place to get.
My wife and kids love it, we'regonna go there.
Erich Schramm, MD (34:17):
Yeah.
It can get hot and be warnedit can be hot and spicy.
Michael Bernh (34:21):
I'll tell them to keep it in the negative range.
Cool, man.
Erich Schramm, MD (34:24):
Cool.
Anything else uh you want toput out there?
Michael Bernhardt, MD (34:27):
I think we've covered pretty much
everything you can cover.
Erich Schramm, MD (34:30):
We used all the big words that could
possibly come to mind on
Michael Bernhardt, MD (34:33):
a lot of syllables for a
Friday afternoon.
Erich Schramm, MD (34:35):
Maybe we've got to look up some things too
to make sure we're we're ontrack.
But thanks again, Mike.
It's always such a pleasure towork with you.
Mi (34:41):
My pleasure too man, enjoyed it.
Erich Schramm, MD (34:42):
We'll see you.
Announcement (34:43):
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