June 11, 2025 • 34 mins
Dermatologist Dr. Michael Bernhardt joins Dr. Eric Schramm to discuss hidradenitis suppurativa (HS), a debilitating skin condition that affects skin creases such as the armpits and groin. HS is an inflammatory condition that can be misdiagnosed for years. New medications target the underlying inflammation. Treatments are currently in clinical trials as part of an effort to tackle the last of the "three-headed monsters" in dermatology.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Announcer (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.
Dr. Erich Schramm (00:11):
Hello and welcome back to the MedEvidence
podcast.
I'm your host, Dr.
Erich Schramm, sitting in forDr.
Koren today.
For those who don't know me,I'm a board-certified family
physician and longtime clinicalresearch investigator with
ECNORE Clinical Research Group.
I'm also a seasoned cannabisphysician involved in helping
people following their healingjourney with medical marijuana.
(00:33):
I'm very excited to be heretoday with one of my favorite
dermatologists, Dr MichaelBernhardt.
Dr Bernhardt and I go back many, many years.
He never gets tired of hearingthe story about me being that
family practice resident
Dr. Michael Bernhardt (00:49):
One of the smartest they ever had.
Dr. Erich Schramm (00:51):
Well, he's very generous, but recalling a
very, very good experience withmy clinical dermatology rotation
and Mike was a fantasticteacher, of course, but
importantly he was a really goodrole model, you know,
demonstrating empathetic,patient-centered care.
I learned a lot from Mike
Dr. Michael Bernhardt (01:12):
Thank you .
Dr. Erich Schramm (01:13):
And still do I get an opportunity to work
with you every Friday afternoon,which is another extension, I
would think of your teaching,which we can talk about.
Your backgroundSo, for those who don't know Dr.
Michael Bernhardt, he's beenpracticing clinical dermatology
(01:33):
for several decades.
In addition, he is a veryseasoned clinical investigator,
as I've alluded to, and I've hadthe pleasure of collaborating
on a number of studies with Mike.
In addition, he's got extensivebackground in clinical
education and medical educationand just recently completed his
three-year stint at the FloridaState University teaching
(01:56):
residents, and that is no smalltask, I would say.
So you're kind of this triplethreat in the clinical world of
research, clinical practice and,as well as doing your academics
.
So one of the things we'reexcited to be talking about
today is hydradenitissuppurativa Now, that's a
(02:18):
mouthful, so we like to refer toit as HS, and perhaps you could
give us a little idea aboutHS-101.
Dr. Michael Bernhardt (02:26):
Sure, sure, I'd be glad to.
But before we start on HS, Ijust got to tell you this stress
ball is the perfect stress ballfor a dermatologist because
it's called Molecool M-O-L-EC-O-L-L Molecule Not molecule,
but molecoll.
So I highly recommend this forall you stressed out
(02:48):
dermatologists.
Dr. Erich Schramm (02:49):
There we go.
Dr. Michael Bernhardt (02:49):
Very good , all right.
So we're going to talk a littlebit about HS.
So the cool thing in the last 10or 15 years that we've done is
it used to be what I used tocall the three-headed monster in
dermatology.
We'd have people with severepsoriasis, severe eczema or
atopic dermatitis andhidradenitis.
(03:10):
And we've really come a longway, largely because of some of
the research that's done inclinical facilities like this
with clinical trials.
We had a lot of patients on theclinical trials for psoriasis.
We did some of the phase 2 andphase 3s for atopic dermatitis.
Now we're dealing with the lastof the three-headed monsters
(03:32):
and we're just now bringing itinto the modern era of treatment
with things other thanantibiotics.
So Hidradenitis; All right, solet's you know, if you guys know
me, you know I can't freeassociate and think without
being able to draw, because itjust kind of facilitates a whole
thought process.
So this is the skin.
(03:54):
The epidermis has severallayers to it and then within the
epidermis you've got the hairfollicle, and feeding into the
hair follicle is oil gland, whatwe call the sebaceous gland.
This is a little dermalpapillae, which is a bunch of
blood vessels and collagen,which has all these little
chemical intermediators that wecall cytokines, which are like
(04:16):
cell and cell signals thatstimulate the hair shaft to grow
.
Okay, and at the same time thatthe hair shaft is stimulated to
grow, basically the same cellsthat line the epidermis will
also line the follicle.
Dr. Erich Schramm (04:32):
And some people are more follically
challenged than others.
I understand Preaching to thechoir.
I know I was going to say maybethat's the next four-headed
monster to tackle, right?
if I say hair today, gonetomorrow.
I know from personal experience.
So this is the oil gland andwhat basically happens in
(04:54):
hidradenitis.
Let's go clinical first beforeI draw.
The average person withhidradenitis starts with lesions
, typically in their teens, andit'll go for eight to 10 years
before that person's diagnosed.
These lesions are normallyfound in what we call the fusion
planes, the armpit, the areaunder the breast, the crease of
(05:18):
the groin and the perianalcrease.
That's the usual hot spots andwhat'll happen is a person will
present to their family, they'llpresent to the emergency room
or urgent care with boils andthey'll get treated as boils.
They get lanced, they getdrained, they get put on an
antibiotic and this will go onfor typically 8 to 10 years
(05:38):
before someone puts it togetherand says, hey, wait a minute,
we've got the same lesionsrecurring in similar areas that
are leaving tracks and scarring,leaving draining areas, and
it's always in that same spot.
You know the armpit, theinframammary crease.
Boom, it's hidradenitis.
And that's really the clinicalhallmark of hidradenitis
(05:58):
Recurrent, quote-unquoteabscesses and boils.
Same area goes on for a longtime.
Now why does it happen?
Well, these cells that line thefollicle, they swell up and
form plugs and there's a lot ofthings that these cells will
overreact to.
Smoking is one, nicotine is one.
(06:20):
Hormones testosterone,progesterone can drive it.
Metabolic syndrome morbidobesity can drive that.
We can get into more detailsabout that in a little while.
But those are the clinicaldrivers.
All right Now seen, I understand, a little
more so in women than men.
(06:40):
Is that your typical experience?
Dr. Michael Bernhardt (06:42):
Yeah, my, experience is it's mostly
females.
You know, when you look at someof the clinical trials, a lot
of clinical trial data will beskewed.
A lot of them, you know, ispredominantly Caucasian
community in clinical trials.
But my own personal experience,overwhelmingly the
African-American community isoverrepresented with this
condition and usually hasseveral underlying comorbidities
(07:05):
obesity, diabetes that tend todrive this Metabolic syndrome,
non-alcoholic steatohepatitis.
We tend to see all that kind ofoverlap.
Dr. Erich Schramm (07:15):
How would you compare or contrast this to
acne?
Dr. Michael Bernhardt (07:19):
So in the old days, back when I was a
resident um, we used to call itacne inversa right, because it's
not in the face or back, it'sin these inverse areas, um, and
in certain ways it overlaps.
But when we start talking aboutthe cytokines, the cytokine
(07:39):
soup in hidradenitis is a littlebit different than what we see
in that acne.
Of course, they're both bothneutrophil-mediated conditions,
right, they're both due tooverexcitation, shall we say, of
the oil secretion apparatus,but the cytokine milieu is a
little bit different.
Dr. Erich Schramm (07:58):
Okay, we can talk a little bit more about
that a little bit later.
But also to underscore inprimary care we treat a lot of
this.
See, you treat a lot of thisand this can be really
devastating to patients.
I mean, it's painful scarformation, very poor quality of
life for those patients withthis.
Dr. Michael Bernhardt (08:18):
I've seen people's lives totally
destroyed when you start talkingto people about it.
Patients cannot marry, theycan't have a normal dating life
or sex life.
They have to be judicious aboutwhat kind of work they do
because, if God forbid, you goin and get a great new corporate
job and you have a bunch ofthese abscesses that decide to
(08:39):
spontaneously open a drain andrelease a foul odor while you're
in the middle of a boardmeeting.
It's going to be tough formaintenance.
So in terms of the areas ofinvolvement, right, it's always
and forgive my drawing, I'm nota very good artist but it's
armpits, right inframammarycrease, genital area and the
(09:03):
gluteal crease, and sometimesthey'll be associated with it.
Sometimes they'll also have anassociated pilonidal cyst.
So when you see recurrent cropsof abscesses in that area, I
mean bang, that's hidradenitisuntil proven otherwise.
Dr. Erich Schramm (09:16):
Right and back 20 years ago as a rotating
resident, we might have beenlooking at, you know, topical
compresses, oral antibiotics.
I won't say that's primitive.
Maybe looking back now it seemskind of sort of primitive, but
we just didn't have a whole lotto offer those patients.
Dr. Michael Bernhardt (09:37):
We didn't , and really up until two, three
years ago it was the same thingOral antibiotics, particularly
doxycycline, because it drivesdown some of these enzymes
called metalloproteinases thatupregulate inflammatory markers.
So we'd use a lot ofdoxycycline.
We would use metformin to blockthe insulin growth factor.
(09:58):
One pathway Humira was a hugefirst step in the right
direction because Humira, whichis a TNF inhibitor, was the
first FDA-approved biologic thathad some impact.
And what we do is we quantifythese lesions in terms of what's
called a high scar, HISCR,which is hidradenitis
(10:21):
remediation, basically.
And what are we looking at?
We're looking at a reduction ofabscesses, nodules and tracts,
and so if you have a 50%reduction of these abscesses and
nodules, you've achieved whatthey call a HISCR 50, 75%, HISCR
75, and so on and so forth.
So Humira was great because itwas the first drug that gave us
(10:42):
a HISCR 50.
It actually worked.
It was wonderful.
And then, when the pandemic hit, the FDA got so slammed and so
overworked with things relatedto COVID that a lot of non-COVID
things got pushed on the backburner.
So several drugs that we werewaiting for approval.
One was secukinumab, which ismarketed as Cosentyx, and
(11:05):
bimekizumba, which is Bimzelx,which involved 17 A inhibitors
finally got the FDA approval andthese drugs are kind of putting
us in the modern era now.
Dr. Erich Schramm (11:15):
Right, and you were already talking about
some of the bad actor cytokinesthat we often talk about when we
have time on Fridays when wehave an opportunity to do that.
But getting back to theoriginal Humira as a monoclonal
antibody was a real game changerand we talked about that also
(11:36):
in treating psoriasis.
Dr. Michael Bernhardt (11:38):
Oh, it was a huge game changer, right.
Dr. Erich Schramm (11:41):
And then, consequently, you know, do you
see the newer agents as the newand improved version of Humira,
or just a different version.
Dr. Michael Bernhardt (11:52):
Humira's a really cool.
Drop my phone, sorry.
That makes for a great podcastand great radio and TV.
Sorry, but it didn't break.
Yeah, these things are a gamechanger because you know there's
several inflammatory mediators.
I call them like the three orfour amigos or the three
musketeers.
(12:12):
They always run together andwherever they run, trouble
follows right.
So whether you're talking aboutinterleukin-6, whether you're
talking about TNF-alpha, whetheryou're talking about 17A 17AF
or the 17AF heterodimer Whereverthese guys go, trouble follows.
And we knew that 17A played arole in the inflammatory cascade
(12:32):
in HS, and some of the newerdata is showing that 17A WAP,
while being a major driver, 17Fand 17AF heterodimer may play
even more of a role ofamplification.
Now, with that being said, thespecific mechanism hasn't been
quantified, so some of this isstill kind of speculative, based
(12:54):
on own personal interpretationof the data, you know.
But we seem to know that thismolecule 17A, 17F, 17AF really
seem to upregulate theinflammatory cascade.
Dr. Erich Schramm (13:09):
Right, and maybe more so than TNF.
Dr. Michael Bernhardt (13:14):
Yeah, well, TNF is upregulated.
Dr. Erich Schramm (13:15):
Right, but maybe 17A and F, being a more
potent stimulator, would you say, is a better target for
treating in terms of itsanti-inflammatory responses.
Dr. Michael Bernhardt (13:28):
I think it's emerging, as in the latest
literature, it's really kind ofevolving into the given a choice
that would be my first choiceto target in terms of mediators.
Now, the problem is that youknow this from practicing
medicine that if the patient hascertain comorbidities, it
(13:50):
carves out certain classes ofdrugs, which is why it's good to
have both the TNF inhibitors aswell as the 17A or 17F
inhibitors, because the personmay have certain premorbidities
that prevent us from using onedrug by the other.
Dr. Erich Schramm (14:05):
Right and kind of the premise for those
therapies is they're monoclonalantibodies directed specifically
at these targets, but not everytreatment out there is a
monoclonal antibody, so whatother ways are there to affect
the inflammatory pathway?
These cascades without.
What are some of the othertherapies out there that don't
(14:27):
involve monoclonal antibodies?
Dr. Michael Bernhardt (14:29):
Well, let's start with the monoclones
first a little bit.
I mean, the nice thing is thatthere's two drugs that target
17A and 17AF, right?
So the sekukinumab targets 17A,bimekizumab targets 17AF.
And that's important becausethere's about because there's an
article that was just publishedin the British Journal that in
(14:50):
the dermis that surrounds thefollicle there's huge amounts of
17 F being secreted by the skinaround the follicle, which is
an upregulatory drives moreinflammation.
Okay, so that's important, butsome people can't tolerate this
drug.
So we know that 17A, which isalso secreted by dendritic cells
(15:12):
, will drive inflammation.
Now you have the 17A, 17AF.
They'll all interact and alsoupregulate TNF, which is also
secreted by some of thesedendritic cells, secreted by
some of these dendritic cells.
So if someone can't toleratethe 17A or the 17AF drug, at
(15:37):
least we have the TNF inhibitorto fall back on.
So when we'relooking at drugs outside of the
biologics right.
So I know that right nowthere's some clinical trials in
the pipeline and the nextgeneration of drugs are going to
be the JAK inhibitors.
We don't have a JAK inhibitororal FDA approved yet for
treating HS.
I've heard some scuttlebuttthat there's things in the
pipeline.
There is a clinical trial goingon.
(15:59):
It's going to be starting, Ithink, here within the next
month or so with a topical JAKinhibitor, ruxolitinib, which is
marketed as Opzelura.
It's a JAK1-2 inhibitor and it'sgoing to be used for mild to
moderate disease, not thosesevere where people have
hypertrophic keloidal scarringand 100 abscesses, but more with
(16:20):
the follicular occlusion andoccasional papules Right, and
that's a topical cream.
It's already got the FDAapproval for things like eczema
and vitiligo.
So it's not, you know, it's notlike the first scene in Hamlet
where the three witches arebrewing something and taking,
you know, the wing of a bat andthe eye of a newt and putting it
together and saying, here, trythis, you know.
(16:42):
So it's not anything like that.
This is already an approveddrug looking at it for an
unfulfilled need and you knowthe theory with HS is if we can
intervene early and catch thingsin the mild to moderate stage
and not let people go to thatsevere stage, you can hopefully
decrease disease progression andat the same time decrease
(17:03):
morbidity.
So in the case of usingtopicals, these would be just at
specific sites, affected sites.
Or do you see that it might havesome greater systemic
absorption that would?
I'll have to check with the medical
science liasons to to see whatthe degree of absorption is.
My overall impression is that Idon't think you can be getting
(17:24):
enough to get a systemic popfrom the drive.
I think that it's just more ofa localized absorption.
Dr. Erich Schramm (17:33):
Cool, maybe you could talk a little bit
about JAK and JAK STAT and whatthe heck is that?
Dr. Michael Bernhardt (17:40):
Oh, JAK STAT All right.
Wasn't it a song by the RollingStones?
No, it was
Dr. Erich Schramm (17:44):
Jumping Jack.
Yes, there you go.
There you go.
Right, that's right.
Yes, there you go.
There you go.
Yeah, right, that's right.
Dr. Michael Bernhardt (17:48):
Somebody got that wrong on Jeopardy last
night.
They asked the final questionwas what band got the best new
performing?
Or it was the quick categorywas Grammys, what band got the
best new performers in the sixthGrammy and then the 35th and
the 67th?
And of course, one person putthe Rolling Stones.
(18:11):
It was the Beatles.
Okay, I'm a big Beatles fan.
Okay, so of course it was theBeatles.
You know that.
So, JAK STAT, has absolutelynothing to do with the Rolling
Stones, so all right, so I'mgoing to have to draw.
Dr. Erich Schramm (18:23):
Okay, there we go.
I was hoping you were going topull that out now.
Dr. Michael Bernhardt (18:27):
Yeah, it shuts me up, right?
If I'm drawing and I have myback, I can't be talking, right,
all right?
So everybody, get your cup ofcoffee and start waking up, all
right?
So here we go.
So let's pretend that this is acell and let's pretend, for the
sake of argument, that this iswhat we call a Th17 cell.
Dr. Erich Schramm (18:50):
T helper 17.
That's part of the immunesystem.
Dr. Michael Bernhardt (18:54):
There are mainly three classes of active
cells and inflammation for ourpurposes, right Th1, cells and
inflammation for our purposes,right TH1, that drives the type
1 pathway.
Th2, which drives the eczemapathway, interleukens 4,13, so
(19:18):
on and so forth, and then theTH17 cells which drive the IL17
pathway .
Right.
We talked about that inpsoriasis as well.
So we're going to pretend that this lousy
drawing of a chocolate chipcookie is really a Th17 cell.
And if you in your mind's eyevisualize like a beach ball with
the port that you put yourmouth on to blow the beach ball
(19:39):
up, so that port is what we callthe cell receptor.
So the receptor will bindcirculating things that float in
the bloodstream.
In this case these things areinterleukin-17 molecules, which
act as an antigen.
So what's an antigen?
(19:59):
Something that stimulates areaction.
So the antigen, the 17 antigen,binds to the receptor.
And when that antigen binds tothe receptor it activates the
receptor.
So that's a separate one-hourlecture I'll avoid, but let's
just say it activates thereceptor.
And in the course of activatingthe receptor there are these
(20:20):
little enzymes that sit on thereceptor, kind of like if you
picture a stick with a glob ofhoney on it, the glob of honey
would be the JAK enzyme system.
Okay, so when these enzymes getactivated, there's another set
of enzymes within the cellcalled STAT S-T-A-T, signal
(20:47):
transduction and translation.
They will automatically jointogether and then move to the
cell nucleus where they induceupregulation of the inflammatory
molecule.
So the way I like to describeit is the receptor gets
activated.
So, in other words, thecatcher's mit has caught the
(21:09):
baseball.
So, the baseball being theantigen, the catcher's mitt has
caught the baseball and in thecourse of catching the baseball,
instead of bringing your armback and throwing the ball, the
receptor gets activated and theSTATS join together.
I'd like to say boy meets girl,they run off to a nice happy
place, which is the nucleus, andthey make this Interleukin-17.
Dr. Erich Schramm (21:29):
The baby comes out, okay.
Dr. Michael Bernhardt (21:30):
Right, and that's what drives the
inflammation that we see prettymuch in hidradenitis as well as
psoriasis.
Dr. Erich Schramm (21:37):
Right.
So right now you could look atthat and say OK, well, there's
two things you could do toaffect that.
One would be to block IL-17with an antibody or,
Or we could go back and look atsome of these intracellular
mechanisms and look at that andthink that might be a really
good opportunity, because youknow thinking about JAK what
(22:00):
some of the bad actors that JAKproduces in where we talked
about IL-1, TNF, it's a longlist of cytokines that JAK
produces, not just IL-17, but itproduces a wide variety of bad
actors there.
Dr. Michael Bernhardt (22:21):
As I'd say, the whole enchilada.
Dr. Erich Schramm (22:27):
What would be the potential downside if you
shut JAK down altogether?
Would there be any necessarilydownside?
Dr. Michael Bernhardt (22:32):
Yeah, I mean, all drugs have side
effects, right, otherwise they'dbe sold in the candy counter.
So when you're blocking JAK,there's all sorts of things that
you have to be cognizant ofright.
JAK inhibitors affect certainblood counts, platelet counts,
lipid profiles, the main thingthat we worry about,
particularly in people over theage of 65, and this is more with
(22:53):
the pills, this isn't reallywith the cream, this is more
with the pills, although the FDAhas mandated a class-wide
warning, even with the cream,that we have to be just as
vigilant.
But the reality of the realityscope is people are much more at
risk to severe side effectsfrom the pills than they are
from the cream.
All right, so do we worry aboutdeep vein thrombosis.
(23:18):
Pulmonary Embolism,cardiovascular disease.
I just reviewed an articleyesterday, it came out in May
Journal of Clinical Allergy andImmunology where it showed that
most of the time when you're onthese pills, in younger people,
the side effects profile isconsidered manageable.
When you get into the over 65cohort, these drugs have to be
used appropriately with moderateto severe disease with a good
(23:42):
history, good physical exam,making sure there's no
predisposing factors, and usedwith caution.
And it's our obligation aslearned intermediaries to
transmit this risk benefit tothe patient and their potential
surviving spouse, depending onthe circumstance.
Dr. Erich Schramm (24:01):
Right and to be clear, when you're talking
about oral medications, you'respecifically referring to the
JAK inhibitors.
Dr. Michael Bernhardt (24:05):
They're all JAK inhibitors Correct.
So I mean they're helpful.
Dr. Erich Schramm (24:10):
What would be a few examples of that, just so
people might have heard,
Dr. Michael Bernhardt (24:14):
severe atopic dermatitis.
You know there are several drugsalready approved, FDA approved,
that are JAK inhibitors andthey're game changers for people
, the life-changing drugs.
That's we're in dermatology, weuse it the most Now the topical
, which is the same one thatwe're going to be doing the
clinical trial on for topicalhidradenitis, mild-moderate
(24:36):
hidadrenitis.
The topical is a great drug.
It's a great drug.
We use it for atopic dermatitisand vitiligo.
It's been a huge game changerfor vitiligo.
I mean, we had nothing thatworked for vitiligo, zip, zero
and nada.
And up until about two or threeyears ago, people came in with
vitiligo.
The spiel they get from me ishey, if it's been there longer
(24:58):
than two years, good luck.
Well, we've turned that around,you know, with the topical JAK
inhibitor, topical ruxolitinib,we've got people repigmenting
and it's amazing, there'snothing short of amazing, and
hopefully we can achieve thesame thing in mild to moderate
hidradenitis by using thetopical JAK, without having to
(25:19):
get into some of the systemicconcerns.
Right, you know it's FDAapproved down to age of 12.
So it's appropriate foradolescence.
So hopefully this will be anice addition to the
armamentarium.
Dr. Erich Schramm (25:33):
Right.
Well, let me ask you aninvestigator question, because
occasionally patients will readabout this and say hey, we know
that this topical works for thiscondition and this condition.
Why can't we just, why can'tyou just prescribe it for, hey,
this other condition, right, whycan't?
If it works for vitiligo andatopic derm, hey, just write me
a script for my HS.
(25:55):
Why can't we just do that?
Dr. Michael Bernhardt (25:58):
It doesn't have the FDA approval,
there's no scientific data,there's no randomized clinical
trials that says, hey, it'sgoing to work, right, you know.
And these things are expensiveand the side effect risks, and
that's what I mean.
Everything has to be usedappropriately and that's the
beauty of doing the randomizedclinical trials, so then we can
know that we're giving this drugto this patient for a good
(26:20):
reason, right, with ananticipation of results.
Dr. Erich Schramm (26:25):
Right.
Now.
Of course, as investigators,you know we have a certain level
of reassurance when we arealready familiar with a
medication or a compound and say, OK, you know, we've got a lot
of experience with this, but,your understanding, we're
looking at that in a differentapplication, so you can't just
go and decide.
You shouldn't be just going anddeciding.
(26:45):
you're going to treat peoplewithout having a good
understanding about the approvalcost
Dr. Michael Bernhardt (26:51):
If you go off label and just shoot from
the hip.
I mean, usually you want to doa literature search first and
just make sure there's someappropriate literature Like, for
example, androgenetic alopecia.
Dr. Erich Schramm (27:08):
For those of you that said we're all pointed
at our relatively hair-freescalps.
Dr. Michael Bernhardt (27:15):
So like for androgenetic, alopecia and I
had this discussion with atleast two people this morning.
Right Off-label use of low-doseminoxidil it works.
It's great Is a quackery to useit because there's no FDA
approval.
No, the drug went generic.
Once a drug goes generic, nocompany is going to pony up the
money that it costs to run therandomized clinical trials and
(27:36):
go through the FDA hurdles Okay,fine.
But you can pull out 10 or 15articles which there are that
show, hey, this works.
And here's the side effectprofile.
So you're not just makingsomething up and it works.
It works well.
There's risks when you get overa certain dosage, but for by
and large low-dose drug for guysand young men that have hair
(27:57):
loss, it's a great drug.
People, alopecia areata, it's agreat drug.
It works.
Here's your side effect profile.
But you're not just makingsomething up.
You've done the literaturesearch.
You've pulled 10 or 15 articles, you've read the risk-benefit
ratio and you can have anintelligent discussion with a
patient.
So that's the differencebetween just saying, yeah, let's
(28:19):
just try this.
40 years ago you could do that.
But what was this joke that Iheard?
It's not a joke.
There was a story back in themid-1970s that, the way that
methotrexate got the approvalfrom the FDA for psoriasis, a
group of dermatologists went upto the FDA and said we'd like to
use this for psoriasis.
Okay, that won't happen.
(28:44):
Now, boys, that's not happeninganymore.
But half a century ago that'swhat people did to start using
drugs.
Hey, this worked.
I've used it on a dozenpatients.
Everybody's doing great.
It's getting approved, okay,fine, that doesn't happen
anymore.
So, like, when we do this trial, we'll be one site.
There are multiple sites ofinterviews in the AHS trial and
(29:08):
it's randomized, so we don'tknow what cream the person's
getting, because that's what wecall blinded.
We don't know what person'susing and we look at the results
and we don't know.
(29:45):
So the results can't be tweaked,there's no cheating in the
system.
It is what it is, if it's not,it's not.
If it works, great.
If not, back to something else.
Dr. Erich Schramm (29:45):
And to be clear
so for us as unbiasedinvestigators, we just want to
get to the truth.
Dr. Michael Bernhardt (29:46):
Which is what science is.
It's exercise in empiricskepticism to search for truth.
Dr. Erich Schramm (29:52):
That's right.
Anything else you'd like to addto your JAK STAT?
Dr. Michael Bernhardt (29:59):
Yeah, I mean I think we covered the JAK
STAT basis right.
JAK get activated, STAT, STATS, translocate to the nucleus and
upregulate cytokine cascade.
So going back to HS, right,let's go back to HS because
there's some cool things aboutHS.
So, from my readings and mythought process, HS, I think, is
(30:23):
a two-phase disease and that'swhy it's been so challenging to
treat right.
So you have the initialinflammatory phases, which is
when people come in with thedraining tracts and the big
tender lumps and bumps right,what we call abscesses and
nodules, and that's reallydriven by 17A and 17AF, at least
(30:43):
based on what we see on currentresearch levels.
And then what happens is ittransforms and turns into this
scarring process which can bequite severe.
I mean, some of these scars areso bad that people can't lift
their arm.
If it's in the axillary creaseor what we call the armpit, they
have restriction of legmovement if it's in the groin,
(31:06):
and that, based on what I'veread, seems to be a different
set of chemical mediators thatseems to be a little bit of
interleukin-1 and transformationgrowth factor beta.
That's trying to for some crazymeans trying to get the skin to
recreate the epidermis insidethe dermis, inside the outer
layer and the lower layer.
(31:26):
Why would it be doing that?
You know the computer system ismisprogrammed, obviously.
So the thinking is that if youcan shut down the inflammation
in the 17A, 17AF phase, youdon't get to the interleukin-1
transformation growth factorphase, so you don't get the big
scarring.
And that's what we're reallytrying to prevent.
Dr. Erich Schramm (31:46):
All right, so you're trying to back to what I
meant when we were looking atyour drawing.
I said thinking in terms oftrying to treat things more
upstream.
Right, Try to prevent as muchof that, the inflammatory
cascade.
Dr. Michael Bernhardt (32:00):
Exactly, exactly, yes, and it'll be
really cool to see if thetopical JAK can do as well as
some of the monoclonals.
Now again, the monoclonals arefor the more severe disease.
Dr. Erich Schramm (32:14):
Right yeah.
Dr. Michael Bernhardt (32:15):
But it'd be really interesting to see how
much progress we can make withjust the topical.
That'd be really cool, right,well, this is my new picture.
By the way, I like this.
This is called Snowstorm andHouse.
Dr. Erich Schramm (32:25):
I like that.
You've really accuratelyrecreated tha t.
One of you are many talentsright Educator, researcher,
clinician, that's right, that'sright.
Well, so Mike, get to thatpoint in the interview and I say
, hey, any question you wish I'dasked or anything you'd like to
add to what we've set up tothis point.
Dr. Michael Bernhardt (32:48):
Well restaurant review.
Ah, okay, Good okay, okay, thisis the highlight.
This is what everybody'swanting to find.
I had dinner the other night atM Brothers in Mayo.
I've got to tell you it wasreally good, really good.
I'd give it a five star.
You know, the same people doMatthews and do Medura's.
They have M Brothers and it's aMayo Clinic Absolutely great.
Dr. Erich Schramm (33:12):
Okay.
Dr. Michael Bernhard (33:12):
Absolutely great.
Dr. Erich Schramm (33:14):
Do you have a recommendation?
Dr. Michael Bernhardt (33:16):
I had to steak.
For all you vegetarians, forall you people that are watching
cholesterol.
I had the steak.
Okay, it was pretty good Okay.
Dr. Erich Schramm (33:23):
Okay, so my turn.
Okay, I'm actually a vegetarian, so you're looking right at one
.
How about that?
Dr. Michael Bernhardt (33:27):
What if you had steak?
You're an indirect vegetarianright Because the steak ate the
ketchup.
There you go.
Dr. Erich Schramm (33:33):
That's right.
It that's right.
So I'm going to put a shout outfor the Floridian in St.
Augustine.
Ok, I like this.
It's a great kind of thatFlorida southern comfort cooking
(33:55):
.
It's got a lot of greatvegetarian options and, for
people who eat seafood, lots ofgreat options.
So I'm a go-to all the timethere.
Dr. Michael Bernhardt (33:59):
The Floridian?
Dr. Erich Schramm (34:00):
The Floridian .
Dr. Michael Bernhardt (34:02):
Good to know
Dr. Erich Schramm (34:02):
Yes, sir, all right, so what's our next topic
of discussion going to be inDermotology role?
Dr. Michael Bernhardt (34:08):
What?
do you want to talk about?
Dr. Erich Schramm (34:11):
Well, we're talking about our bald heads,
but until we've got to come upwith something better to help
that,
I'll talk about alopecia.
Okay, I'll talk about the marchof the hair follicles.
Let's do that .
Dr. Michael Bernhardt (34:21):
Sounds good.
Dr. Erich Schramm (34:21):
Cool man, all right, sounds good.
Dr. Michael Bernhardt (34:23):
Hair today going tomorrow.
Dr. Erich Schramm (34:24):
There you go, all right.
Announcer (34:25):
Thanks for joining the MedEvidence podcast.
To learn more, head over toMedEvidence.
com or subscribe to our podcaston your favorite podcast
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.
Dr. Erich Schramm (00:11):
Hello and welcome back to the MedEvidence
podcast.
I'm your host, Dr.
Erich Schramm, sitting in forDr.
Koren today.
For those who don't know me,I'm a board-certified family
physician and longtime clinicalresearch investigator with
ECNORE Clinical Research Group.
I'm also a seasoned cannabisphysician involved in helping
people following their healingjourney with medical marijuana.
(00:33):
I'm very excited to be heretoday with one of my favorite
dermatologists, Dr MichaelBernhardt.
Dr Bernhardt and I go back many, many years.
He never gets tired of hearingthe story about me being that
family practice resident
Dr. Michael Bernhardt (00:49):
One of the smartest they ever had.
Dr. Erich Schramm (00:51):
Well, he's very generous, but recalling a
very, very good experience withmy clinical dermatology rotation
and Mike was a fantasticteacher, of course, but
importantly he was a really goodrole model, you know,
demonstrating empathetic,patient-centered care.
I learned a lot from Mike
Dr. Michael Bernhardt (01:12):
Thank you .
Dr. Erich Schramm (01:13):
And still do I get an opportunity to work
with you every Friday afternoon,which is another extension, I
would think of your teaching,which we can talk about.
Your backgroundSo, for those who don't know Dr.
Michael Bernhardt, he's beenpracticing clinical dermatology
(01:33):
for several decades.
In addition, he is a veryseasoned clinical investigator,
as I've alluded to, and I've hadthe pleasure of collaborating
on a number of studies with Mike.
In addition, he's got extensivebackground in clinical
education and medical educationand just recently completed his
three-year stint at the FloridaState University teaching
(01:56):
residents, and that is no smalltask, I would say.
So you're kind of this triplethreat in the clinical world of
research, clinical practice and,as well as doing your academics
.
So one of the things we'reexcited to be talking about
today is hydradenitissuppurativa Now, that's a
(02:18):
mouthful, so we like to refer toit as HS, and perhaps you could
give us a little idea aboutHS-101.
Dr. Michael Bernhardt (02:26):
Sure, sure, I'd be glad to.
But before we start on HS, Ijust got to tell you this stress
ball is the perfect stress ballfor a dermatologist because
it's called Molecool M-O-L-EC-O-L-L Molecule Not molecule,
but molecoll.
So I highly recommend this forall you stressed out
(02:48):
dermatologists.
Dr. Erich Schramm (02:49):
There we go.
Dr. Michael Bernhardt (02:49):
Very good , all right.
So we're going to talk a littlebit about HS.
So the cool thing in the last 10or 15 years that we've done is
it used to be what I used tocall the three-headed monster in
dermatology.
We'd have people with severepsoriasis, severe eczema or
atopic dermatitis andhidradenitis.
(03:10):
And we've really come a longway, largely because of some of
the research that's done inclinical facilities like this
with clinical trials.
We had a lot of patients on theclinical trials for psoriasis.
We did some of the phase 2 andphase 3s for atopic dermatitis.
Now we're dealing with the lastof the three-headed monsters
(03:32):
and we're just now bringing itinto the modern era of treatment
with things other thanantibiotics.
So Hidradenitis; All right, solet's you know, if you guys know
me, you know I can't freeassociate and think without
being able to draw, because itjust kind of facilitates a whole
thought process.
So this is the skin.
(03:54):
The epidermis has severallayers to it and then within the
epidermis you've got the hairfollicle, and feeding into the
hair follicle is oil gland, whatwe call the sebaceous gland.
This is a little dermalpapillae, which is a bunch of
blood vessels and collagen,which has all these little
chemical intermediators that wecall cytokines, which are like
(04:16):
cell and cell signals thatstimulate the hair shaft to grow
.
Okay, and at the same time thatthe hair shaft is stimulated to
grow, basically the same cellsthat line the epidermis will
also line the follicle.
Dr. Erich Schramm (04:32):
And some people are more follically
challenged than others.
I understand Preaching to thechoir.
I know I was going to say maybethat's the next four-headed
monster to tackle, right?
if I say hair today, gonetomorrow.
I know from personal experience.
So this is the oil gland andwhat basically happens in
(04:54):
hidradenitis.
Let's go clinical first beforeI draw.
The average person withhidradenitis starts with lesions
, typically in their teens, andit'll go for eight to 10 years
before that person's diagnosed.
These lesions are normallyfound in what we call the fusion
planes, the armpit, the areaunder the breast, the crease of
(05:18):
the groin and the perianalcrease.
That's the usual hot spots andwhat'll happen is a person will
present to their family, they'llpresent to the emergency room
or urgent care with boils andthey'll get treated as boils.
They get lanced, they getdrained, they get put on an
antibiotic and this will go onfor typically 8 to 10 years
(05:38):
before someone puts it togetherand says, hey, wait a minute,
we've got the same lesionsrecurring in similar areas that
are leaving tracks and scarring,leaving draining areas, and
it's always in that same spot.
You know the armpit, theinframammary crease.
Boom, it's hidradenitis.
And that's really the clinicalhallmark of hidradenitis
(05:58):
Recurrent, quote-unquoteabscesses and boils.
Same area goes on for a longtime.
Now why does it happen?
Well, these cells that line thefollicle, they swell up and
form plugs and there's a lot ofthings that these cells will
overreact to.
Smoking is one, nicotine is one.
(06:20):
Hormones testosterone,progesterone can drive it.
Metabolic syndrome morbidobesity can drive that.
We can get into more detailsabout that in a little while.
But those are the clinicaldrivers.
All right Now seen, I understand, a little
more so in women than men.
(06:40):
Is that your typical experience?
Dr. Michael Bernhardt (06:42):
Yeah, my, experience is it's mostly
females.
You know, when you look at someof the clinical trials, a lot
of clinical trial data will beskewed.
A lot of them, you know, ispredominantly Caucasian
community in clinical trials.
But my own personal experience,overwhelmingly the
African-American community isoverrepresented with this
condition and usually hasseveral underlying comorbidities
(07:05):
obesity, diabetes that tend todrive this Metabolic syndrome,
non-alcoholic steatohepatitis.
We tend to see all that kind ofoverlap.
Dr. Erich Schramm (07:15):
How would you compare or contrast this to
acne?
Dr. Michael Bernhardt (07:19):
So in the old days, back when I was a
resident um, we used to call itacne inversa right, because it's
not in the face or back, it'sin these inverse areas, um, and
in certain ways it overlaps.
But when we start talking aboutthe cytokines, the cytokine
(07:39):
soup in hidradenitis is a littlebit different than what we see
in that acne.
Of course, they're both bothneutrophil-mediated conditions,
right, they're both due tooverexcitation, shall we say, of
the oil secretion apparatus,but the cytokine milieu is a
little bit different.
Dr. Erich Schramm (07:58):
Okay, we can talk a little bit more about
that a little bit later.
But also to underscore inprimary care we treat a lot of
this.
See, you treat a lot of thisand this can be really
devastating to patients.
I mean, it's painful scarformation, very poor quality of
life for those patients withthis.
Dr. Michael Bernhardt (08:18):
I've seen people's lives totally
destroyed when you start talkingto people about it.
Patients cannot marry, theycan't have a normal dating life
or sex life.
They have to be judicious aboutwhat kind of work they do
because, if God forbid, you goin and get a great new corporate
job and you have a bunch ofthese abscesses that decide to
(08:39):
spontaneously open a drain andrelease a foul odor while you're
in the middle of a boardmeeting.
It's going to be tough formaintenance.
So in terms of the areas ofinvolvement, right, it's always
and forgive my drawing, I'm nota very good artist but it's
armpits, right inframammarycrease, genital area and the
(09:03):
gluteal crease, and sometimesthey'll be associated with it.
Sometimes they'll also have anassociated pilonidal cyst.
So when you see recurrent cropsof abscesses in that area, I
mean bang, that's hidradenitisuntil proven otherwise.
Dr. Erich Schramm (09:16):
Right and back 20 years ago as a rotating
resident, we might have beenlooking at, you know, topical
compresses, oral antibiotics.
I won't say that's primitive.
Maybe looking back now it seemskind of sort of primitive, but
we just didn't have a whole lotto offer those patients.
Dr. Michael Bernhardt (09:37):
We didn't , and really up until two, three
years ago it was the same thingOral antibiotics, particularly
doxycycline, because it drivesdown some of these enzymes
called metalloproteinases thatupregulate inflammatory markers.
So we'd use a lot ofdoxycycline.
We would use metformin to blockthe insulin growth factor.
(09:58):
One pathway Humira was a hugefirst step in the right
direction because Humira, whichis a TNF inhibitor, was the
first FDA-approved biologic thathad some impact.
And what we do is we quantifythese lesions in terms of what's
called a high scar, HISCR,which is hidradenitis
(10:21):
remediation, basically.
And what are we looking at?
We're looking at a reduction ofabscesses, nodules and tracts,
and so if you have a 50%reduction of these abscesses and
nodules, you've achieved whatthey call a HISCR 50, 75%, HISCR
75, and so on and so forth.
So Humira was great because itwas the first drug that gave us
(10:42):
a HISCR 50.
It actually worked.
It was wonderful.
And then, when the pandemic hit, the FDA got so slammed and so
overworked with things relatedto COVID that a lot of non-COVID
things got pushed on the backburner.
So several drugs that we werewaiting for approval.
One was secukinumab, which ismarketed as Cosentyx, and
(11:05):
bimekizumba, which is Bimzelx,which involved 17 A inhibitors
finally got the FDA approval andthese drugs are kind of putting
us in the modern era now.
Dr. Erich Schramm (11:15):
Right, and you were already talking about
some of the bad actor cytokinesthat we often talk about when we
have time on Fridays when wehave an opportunity to do that.
But getting back to theoriginal Humira as a monoclonal
antibody was a real game changerand we talked about that also
(11:36):
in treating psoriasis.
Dr. Michael Bernhardt (11:38):
Oh, it was a huge game changer, right.
Dr. Erich Schramm (11:41):
And then, consequently, you know, do you
see the newer agents as the newand improved version of Humira,
or just a different version.
Dr. Michael Bernhardt (11:52):
Humira's a really cool.
Drop my phone, sorry.
That makes for a great podcastand great radio and TV.
Sorry, but it didn't break.
Yeah, these things are a gamechanger because you know there's
several inflammatory mediators.
I call them like the three orfour amigos or the three
musketeers.
(12:12):
They always run together andwherever they run, trouble
follows right.
So whether you're talking aboutinterleukin-6, whether you're
talking about TNF-alpha, whetheryou're talking about 17A 17AF
or the 17AF heterodimer Whereverthese guys go, trouble follows.
And we knew that 17A played arole in the inflammatory cascade
(12:32):
in HS, and some of the newerdata is showing that 17A WAP,
while being a major driver, 17Fand 17AF heterodimer may play
even more of a role ofamplification.
Now, with that being said, thespecific mechanism hasn't been
quantified, so some of this isstill kind of speculative, based
(12:54):
on own personal interpretationof the data, you know.
But we seem to know that thismolecule 17A, 17F, 17AF really
seem to upregulate theinflammatory cascade.
Dr. Erich Schramm (13:09):
Right, and maybe more so than TNF.
Dr. Michael Bernhardt (13:14):
Yeah, well, TNF is upregulated.
Dr. Erich Schramm (13:15):
Right, but maybe 17A and F, being a more
potent stimulator, would you say, is a better target for
treating in terms of itsanti-inflammatory responses.
Dr. Michael Bernhardt (13:28):
I think it's emerging, as in the latest
literature, it's really kind ofevolving into the given a choice
that would be my first choiceto target in terms of mediators.
Now, the problem is that youknow this from practicing
medicine that if the patient hascertain comorbidities, it
(13:50):
carves out certain classes ofdrugs, which is why it's good to
have both the TNF inhibitors aswell as the 17A or 17F
inhibitors, because the personmay have certain premorbidities
that prevent us from using onedrug by the other.
Dr. Erich Schramm (14:05):
Right and kind of the premise for those
therapies is they're monoclonalantibodies directed specifically
at these targets, but not everytreatment out there is a
monoclonal antibody, so whatother ways are there to affect
the inflammatory pathway?
These cascades without.
What are some of the othertherapies out there that don't
(14:27):
involve monoclonal antibodies?
Dr. Michael Bernhardt (14:29):
Well, let's start with the monoclones
first a little bit.
I mean, the nice thing is thatthere's two drugs that target
17A and 17AF, right?
So the sekukinumab targets 17A,bimekizumab targets 17AF.
And that's important becausethere's about because there's an
article that was just publishedin the British Journal that in
(14:50):
the dermis that surrounds thefollicle there's huge amounts of
17 F being secreted by the skinaround the follicle, which is
an upregulatory drives moreinflammation.
Okay, so that's important, butsome people can't tolerate this
drug.
So we know that 17A, which isalso secreted by dendritic cells
(15:12):
, will drive inflammation.
Now you have the 17A, 17AF.
They'll all interact and alsoupregulate TNF, which is also
secreted by some of thesedendritic cells, secreted by
some of these dendritic cells.
So if someone can't toleratethe 17A or the 17AF drug, at
(15:37):
least we have the TNF inhibitorto fall back on.
So when we'relooking at drugs outside of the
biologics right.
So I know that right nowthere's some clinical trials in
the pipeline and the nextgeneration of drugs are going to
be the JAK inhibitors.
We don't have a JAK inhibitororal FDA approved yet for
treating HS.
I've heard some scuttlebuttthat there's things in the
pipeline.
There is a clinical trial goingon.
(15:59):
It's going to be starting, Ithink, here within the next
month or so with a topical JAKinhibitor, ruxolitinib, which is
marketed as Opzelura.
It's a JAK1-2 inhibitor and it'sgoing to be used for mild to
moderate disease, not thosesevere where people have
hypertrophic keloidal scarringand 100 abscesses, but more with
(16:20):
the follicular occlusion andoccasional papules Right, and
that's a topical cream.
It's already got the FDAapproval for things like eczema
and vitiligo.
So it's not, you know, it's notlike the first scene in Hamlet
where the three witches arebrewing something and taking,
you know, the wing of a bat andthe eye of a newt and putting it
together and saying, here, trythis, you know.
(16:42):
So it's not anything like that.
This is already an approveddrug looking at it for an
unfulfilled need and you knowthe theory with HS is if we can
intervene early and catch thingsin the mild to moderate stage
and not let people go to thatsevere stage, you can hopefully
decrease disease progression andat the same time decrease
(17:03):
morbidity.
So in the case of usingtopicals, these would be just at
specific sites, affected sites.
Or do you see that it might havesome greater systemic
absorption that would?
I'll have to check with the medical
science liasons to to see whatthe degree of absorption is.
My overall impression is that Idon't think you can be getting
(17:24):
enough to get a systemic popfrom the drive.
I think that it's just more ofa localized absorption.
Dr. Erich Schramm (17:33):
Cool, maybe you could talk a little bit
about JAK and JAK STAT and whatthe heck is that?
Dr. Michael Bernhardt (17:40):
Oh, JAK STAT All right.
Wasn't it a song by the RollingStones?
No, it was
Dr. Erich Schramm (17:44):
Jumping Jack.
Yes, there you go.
There you go.
Right, that's right.
Yes, there you go.
There you go.
Yeah, right, that's right.
Dr. Michael Bernhardt (17:48):
Somebody got that wrong on Jeopardy last
night.
They asked the final questionwas what band got the best new
performing?
Or it was the quick categorywas Grammys, what band got the
best new performers in the sixthGrammy and then the 35th and
the 67th?
And of course, one person putthe Rolling Stones.
(18:11):
It was the Beatles.
Okay, I'm a big Beatles fan.
Okay, so of course it was theBeatles.
You know that.
So, JAK STAT, has absolutelynothing to do with the Rolling
Stones, so all right, so I'mgoing to have to draw.
Dr. Erich Schramm (18:23):
Okay, there we go.
I was hoping you were going topull that out now.
Dr. Michael Bernhardt (18:27):
Yeah, it shuts me up, right?
If I'm drawing and I have myback, I can't be talking, right,
all right?
So everybody, get your cup ofcoffee and start waking up, all
right?
So here we go.
So let's pretend that this is acell and let's pretend, for the
sake of argument, that this iswhat we call a Th17 cell.
Dr. Erich Schramm (18:50):
T helper 17.
That's part of the immunesystem.
Dr. Michael Bernhardt (18:54):
There are mainly three classes of active
cells and inflammation for ourpurposes, right Th1, cells and
inflammation for our purposes,right TH1, that drives the type
1 pathway.
Th2, which drives the eczemapathway, interleukens 4,13, so
(19:18):
on and so forth, and then theTH17 cells which drive the IL17
pathway .
Right.
We talked about that inpsoriasis as well.
So we're going to pretend that this lousy
drawing of a chocolate chipcookie is really a Th17 cell.
And if you in your mind's eyevisualize like a beach ball with
the port that you put yourmouth on to blow the beach ball
(19:39):
up, so that port is what we callthe cell receptor.
So the receptor will bindcirculating things that float in
the bloodstream.
In this case these things areinterleukin-17 molecules, which
act as an antigen.
So what's an antigen?
(19:59):
Something that stimulates areaction.
So the antigen, the 17 antigen,binds to the receptor.
And when that antigen binds tothe receptor it activates the
receptor.
So that's a separate one-hourlecture I'll avoid, but let's
just say it activates thereceptor.
And in the course of activatingthe receptor there are these
(20:20):
little enzymes that sit on thereceptor, kind of like if you
picture a stick with a glob ofhoney on it, the glob of honey
would be the JAK enzyme system.
Okay, so when these enzymes getactivated, there's another set
of enzymes within the cellcalled STAT S-T-A-T, signal
(20:47):
transduction and translation.
They will automatically jointogether and then move to the
cell nucleus where they induceupregulation of the inflammatory
molecule.
So the way I like to describeit is the receptor gets
activated.
So, in other words, thecatcher's mit has caught the
(21:09):
baseball.
So, the baseball being theantigen, the catcher's mitt has
caught the baseball and in thecourse of catching the baseball,
instead of bringing your armback and throwing the ball, the
receptor gets activated and theSTATS join together.
I'd like to say boy meets girl,they run off to a nice happy
place, which is the nucleus, andthey make this Interleukin-17.
Dr. Erich Schramm (21:29):
The baby comes out, okay.
Dr. Michael Bernhardt (21:30):
Right, and that's what drives the
inflammation that we see prettymuch in hidradenitis as well as
psoriasis.
Dr. Erich Schramm (21:37):
Right.
So right now you could look atthat and say OK, well, there's
two things you could do toaffect that.
One would be to block IL-17with an antibody or,
Or we could go back and look atsome of these intracellular
mechanisms and look at that andthink that might be a really
good opportunity, because youknow thinking about JAK what
(22:00):
some of the bad actors that JAKproduces in where we talked
about IL-1, TNF, it's a longlist of cytokines that JAK
produces, not just IL-17, but itproduces a wide variety of bad
actors there.
Dr. Michael Bernhardt (22:21):
As I'd say, the whole enchilada.
Dr. Erich Schramm (22:27):
What would be the potential downside if you
shut JAK down altogether?
Would there be any necessarilydownside?
Dr. Michael Bernhardt (22:32):
Yeah, I mean, all drugs have side
effects, right, otherwise they'dbe sold in the candy counter.
So when you're blocking JAK,there's all sorts of things that
you have to be cognizant ofright.
JAK inhibitors affect certainblood counts, platelet counts,
lipid profiles, the main thingthat we worry about,
particularly in people over theage of 65, and this is more with
(22:53):
the pills, this isn't reallywith the cream, this is more
with the pills, although the FDAhas mandated a class-wide
warning, even with the cream,that we have to be just as
vigilant.
But the reality of the realityscope is people are much more at
risk to severe side effectsfrom the pills than they are
from the cream.
All right, so do we worry aboutdeep vein thrombosis.
(23:18):
Pulmonary Embolism,cardiovascular disease.
I just reviewed an articleyesterday, it came out in May
Journal of Clinical Allergy andImmunology where it showed that
most of the time when you're onthese pills, in younger people,
the side effects profile isconsidered manageable.
When you get into the over 65cohort, these drugs have to be
used appropriately with moderateto severe disease with a good
(23:42):
history, good physical exam,making sure there's no
predisposing factors, and usedwith caution.
And it's our obligation aslearned intermediaries to
transmit this risk benefit tothe patient and their potential
surviving spouse, depending onthe circumstance.
Dr. Erich Schramm (24:01):
Right and to be clear, when you're talking
about oral medications, you'respecifically referring to the
JAK inhibitors.
Dr. Michael Bernhardt (24:05):
They're all JAK inhibitors Correct.
So I mean they're helpful.
Dr. Erich Schramm (24:10):
What would be a few examples of that, just so
people might have heard,
Dr. Michael Bernhardt (24:14):
severe atopic dermatitis.
You know there are several drugsalready approved, FDA approved,
that are JAK inhibitors andthey're game changers for people
, the life-changing drugs.
That's we're in dermatology, weuse it the most Now the topical
, which is the same one thatwe're going to be doing the
clinical trial on for topicalhidradenitis, mild-moderate
(24:36):
hidadrenitis.
The topical is a great drug.
It's a great drug.
We use it for atopic dermatitisand vitiligo.
It's been a huge game changerfor vitiligo.
I mean, we had nothing thatworked for vitiligo, zip, zero
and nada.
And up until about two or threeyears ago, people came in with
vitiligo.
The spiel they get from me ishey, if it's been there longer
(24:58):
than two years, good luck.
Well, we've turned that around,you know, with the topical JAK
inhibitor, topical ruxolitinib,we've got people repigmenting
and it's amazing, there'snothing short of amazing, and
hopefully we can achieve thesame thing in mild to moderate
hidradenitis by using thetopical JAK, without having to
(25:19):
get into some of the systemicconcerns.
Right, you know it's FDAapproved down to age of 12.
So it's appropriate foradolescence.
So hopefully this will be anice addition to the
armamentarium.
Dr. Erich Schramm (25:33):
Right.
Well, let me ask you aninvestigator question, because
occasionally patients will readabout this and say hey, we know
that this topical works for thiscondition and this condition.
Why can't we just, why can'tyou just prescribe it for, hey,
this other condition, right, whycan't?
If it works for vitiligo andatopic derm, hey, just write me
a script for my HS.
(25:55):
Why can't we just do that?
Dr. Michael Bernhardt (25:58):
It doesn't have the FDA approval,
there's no scientific data,there's no randomized clinical
trials that says, hey, it'sgoing to work, right, you know.
And these things are expensiveand the side effect risks, and
that's what I mean.
Everything has to be usedappropriately and that's the
beauty of doing the randomizedclinical trials, so then we can
know that we're giving this drugto this patient for a good
(26:20):
reason, right, with ananticipation of results.
Dr. Erich Schramm (26:25):
Right.
Now.
Of course, as investigators,you know we have a certain level
of reassurance when we arealready familiar with a
medication or a compound and say, OK, you know, we've got a lot
of experience with this, but,your understanding, we're
looking at that in a differentapplication, so you can't just
go and decide.
You shouldn't be just going anddeciding.
(26:45):
you're going to treat peoplewithout having a good
understanding about the approvalcost
Dr. Michael Bernhardt (26:51):
If you go off label and just shoot from
the hip.
I mean, usually you want to doa literature search first and
just make sure there's someappropriate literature Like, for
example, androgenetic alopecia.
Dr. Erich Schramm (27:08):
For those of you that said we're all pointed
at our relatively hair-freescalps.
Dr. Michael Bernhardt (27:15):
So like for androgenetic, alopecia and I
had this discussion with atleast two people this morning.
Right Off-label use of low-doseminoxidil it works.
It's great Is a quackery to useit because there's no FDA
approval.
No, the drug went generic.
Once a drug goes generic, nocompany is going to pony up the
money that it costs to run therandomized clinical trials and
(27:36):
go through the FDA hurdles Okay,fine.
But you can pull out 10 or 15articles which there are that
show, hey, this works.
And here's the side effectprofile.
So you're not just makingsomething up and it works.
It works well.
There's risks when you get overa certain dosage, but for by
and large low-dose drug for guysand young men that have hair
(27:57):
loss, it's a great drug.
People, alopecia areata, it's agreat drug.
It works.
Here's your side effect profile.
But you're not just makingsomething up.
You've done the literaturesearch.
You've pulled 10 or 15 articles, you've read the risk-benefit
ratio and you can have anintelligent discussion with a
patient.
So that's the differencebetween just saying, yeah, let's
(28:19):
just try this.
40 years ago you could do that.
But what was this joke that Iheard?
It's not a joke.
There was a story back in themid-1970s that, the way that
methotrexate got the approvalfrom the FDA for psoriasis, a
group of dermatologists went upto the FDA and said we'd like to
use this for psoriasis.
Okay, that won't happen.
(28:44):
Now, boys, that's not happeninganymore.
But half a century ago that'swhat people did to start using
drugs.
Hey, this worked.
I've used it on a dozenpatients.
Everybody's doing great.
It's getting approved, okay,fine, that doesn't happen
anymore.
So, like, when we do this trial, we'll be one site.
There are multiple sites ofinterviews in the AHS trial and
(29:08):
it's randomized, so we don'tknow what cream the person's
getting, because that's what wecall blinded.
We don't know what person'susing and we look at the results
and we don't know.
(29:45):
So the results can't be tweaked,there's no cheating in the
system.
It is what it is, if it's not,it's not.
If it works, great.
If not, back to something else.
Dr. Erich Schramm (29:45):
And to be clear
so for us as unbiasedinvestigators, we just want to
get to the truth.
Dr. Michael Bernhardt (29:46):
Which is what science is.
It's exercise in empiricskepticism to search for truth.
Dr. Erich Schramm (29:52):
That's right.
Anything else you'd like to addto your JAK STAT?
Dr. Michael Bernhardt (29:59):
Yeah, I mean I think we covered the JAK
STAT basis right.
JAK get activated, STAT, STATS, translocate to the nucleus and
upregulate cytokine cascade.
So going back to HS, right,let's go back to HS because
there's some cool things aboutHS.
So, from my readings and mythought process, HS, I think, is
(30:23):
a two-phase disease and that'swhy it's been so challenging to
treat right.
So you have the initialinflammatory phases, which is
when people come in with thedraining tracts and the big
tender lumps and bumps right,what we call abscesses and
nodules, and that's reallydriven by 17A and 17AF, at least
(30:43):
based on what we see on currentresearch levels.
And then what happens is ittransforms and turns into this
scarring process which can bequite severe.
I mean, some of these scars areso bad that people can't lift
their arm.
If it's in the axillary creaseor what we call the armpit, they
have restriction of legmovement if it's in the groin,
(31:06):
and that, based on what I'veread, seems to be a different
set of chemical mediators thatseems to be a little bit of
interleukin-1 and transformationgrowth factor beta.
That's trying to for some crazymeans trying to get the skin to
recreate the epidermis insidethe dermis, inside the outer
layer and the lower layer.
(31:26):
Why would it be doing that?
You know the computer system ismisprogrammed, obviously.
So the thinking is that if youcan shut down the inflammation
in the 17A, 17AF phase, youdon't get to the interleukin-1
transformation growth factorphase, so you don't get the big
scarring.
And that's what we're reallytrying to prevent.
Dr. Erich Schramm (31:46):
All right, so you're trying to back to what I
meant when we were looking atyour drawing.
I said thinking in terms oftrying to treat things more
upstream.
Right, Try to prevent as muchof that, the inflammatory
cascade.
Dr. Michael Bernhardt (32:00):
Exactly, exactly, yes, and it'll be
really cool to see if thetopical JAK can do as well as
some of the monoclonals.
Now again, the monoclonals arefor the more severe disease.
Dr. Erich Schramm (32:14):
Right yeah.
Dr. Michael Bernhardt (32:15):
But it'd be really interesting to see how
much progress we can make withjust the topical.
That'd be really cool, right,well, this is my new picture.
By the way, I like this.
This is called Snowstorm andHouse.
Dr. Erich Schramm (32:25):
I like that.
You've really accuratelyrecreated tha t.
One of you are many talentsright Educator, researcher,
clinician, that's right, that'sright.
Well, so Mike, get to thatpoint in the interview and I say
, hey, any question you wish I'dasked or anything you'd like to
add to what we've set up tothis point.
Dr. Michael Bernhardt (32:48):
Well restaurant review.
Ah, okay, Good okay, okay, thisis the highlight.
This is what everybody'swanting to find.
I had dinner the other night atM Brothers in Mayo.
I've got to tell you it wasreally good, really good.
I'd give it a five star.
You know, the same people doMatthews and do Medura's.
They have M Brothers and it's aMayo Clinic Absolutely great.
Dr. Erich Schramm (33:12):
Okay.
Dr. Michael Bernhard (33:12):
Absolutely great.
Dr. Erich Schramm (33:14):
Do you have a recommendation?
Dr. Michael Bernhardt (33:16):
I had to steak.
For all you vegetarians, forall you people that are watching
cholesterol.
I had the steak.
Okay, it was pretty good Okay.
Dr. Erich Schramm (33:23):
Okay, so my turn.
Okay, I'm actually a vegetarian, so you're looking right at one
.
How about that?
Dr. Michael Bernhardt (33:27):
What if you had steak?
You're an indirect vegetarianright Because the steak ate the
ketchup.
There you go.
Dr. Erich Schramm (33:33):
That's right.
It that's right.
So I'm going to put a shout outfor the Floridian in St.
Augustine.
Ok, I like this.
It's a great kind of thatFlorida southern comfort cooking
(33:55):
.
It's got a lot of greatvegetarian options and, for
people who eat seafood, lots ofgreat options.
So I'm a go-to all the timethere.
Dr. Michael Bernhardt (33:59):
The Floridian?
Dr. Erich Schramm (34:00):
The Floridian .
Dr. Michael Bernhardt (34:02):
Good to know
Dr. Erich Schramm (34:02):
Yes, sir, all right, so what's our next topic
of discussion going to be inDermotology role?
Dr. Michael Bernhardt (34:08):
What?
do you want to talk about?
Dr. Erich Schramm (34:11):
Well, we're talking about our bald heads,
but until we've got to come upwith something better to help
that,
I'll talk about alopecia.
Okay, I'll talk about the marchof the hair follicles.
Let's do that .
Dr. Michael Bernhardt (34:21):
Sounds good.
Dr. Erich Schramm (34:21):
Cool man, all right, sounds good.
Dr. Michael Bernhardt (34:23):
Hair today going tomorrow.
Dr. Erich Schramm (34:24):
There you go, all right.
Announcer (34:25):
Thanks for joining the MedEvidence podcast.
To learn more, head over toMedEvidence.
com or subscribe to our podcaston your favorite podcast
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