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Kathryn “Cassie” Torok, MD, director of the Pediatric Scleroderma Clinic at UPMC Children’s Hospital of Pittsburgh, is one of the few doctors in the nation that is considered an expert on pediatric scleroderma and patients will travel from other cities to meet with her. Learn about this uncommon condition and the clinical work and research coming from the Pediatric Scleroderma Clinic.
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Dr. J Williams: This podcast is for informational and educational purposes only and is not to be
considered medical advice for any particular patient. Clinicians must rely on
their own informed clinical judgments when making recommendations for their
patients. Patients in need of medical advice should consult their personal
Dr. Steph Dewar: From UPMC Children's Hospital of Pittsburgh, welcome to That's Pediatrics. I'm
Steph Dewar, one of the hospitalists physicians here at Children's, and codirector of the Pediatric Residency Training Program.
Dr. J Williams: And I'm John Williams, chief of Pediatric Infectious Diseases. And, we are
delighted to welcome as our guest today, Dr. Cassie Torok, a pediatric
rheumatologist and a specialist in pediatric scleroderma. Cassie, welcome to
Dr. C Torok: Thanks, John and Stephanie.
Dr. Steph Dewar: So, Cassie, you have a wide range of clinical and research interests. The one
thing I thought would be useful for folks to hear about is your work with
patients with scleroderma.
Dr. C Torok: Okay, great. So, I'll give you a little bit of background. I was a trainee here, and
during my training and part of my fellowship training, I worked with Dr. Thomas
Medsger, who's a world-renowned scleroderma expert in the adult world. I
followed him and performed research and, in that methodology, really got in
tune with scleroderma and then branched this into pediatric scleroderma, both
localized scleroderma and systemic scleroderma. With that, we started a
pediatric scleroderma clinic in 2012ish, and over time it's expanded. So,
clinically, I'll see these patients on a day-to-day basis. We have weekly
scleroderma clinics right now.
From that, I saw some issues that need to be addressed. Some are clinical issues
as far as day-to-day management and treatment of these patients and then,
also, education. Some patients would come in from different providers being
misdiagnosed or managed in a different way. Then, also, the biology behind the
disease is very unknown. It's not a disease that's tapped into as much as far as
the research realm. So, I was very interested to find out what's driving this
disease and how can we treat it, and how can we treat it better? So, as part of
this scleroderma clinic, we also collect blood specimens on these patients and
follow them longitudinally. Hopefully, then to find biomarkers and other
indicators of what's driving this disease and how we can stop it and also,
hopefully, maybe someday, find a cure.
Dr. J Williams: So, Cassie, you're the director of the Pediatric Scleroderma Clinic and this is a
pretty uncommon disease and, therefore, you have kids coming from short of all
over to see you as an expert. Correct?
Dr. C Torok: Correct. So, this an uncommon condition, so a pediatric rheumatologist, in
general, is not that common to find. But, even an established pediatric
rheumatologist may only see a handful of these patients a year. Maybe one or
two patients. Therefore, if a patient has more severe disease, like linear down
their leg, they're getting joint contractors, some limb length discrepancy, they
would tend to reach out to me, maybe just to discuss management. But, a lot of
the time, the parents would also be appreciative of a visit with me. So, they will
fly out and see me even if it's just a one-time visit, and then I help co-manage
with their pediatric rheumatologist. But, several of the patients after coming to
the Pediatric Scleroderma Clinic actually like to come at least on an annual basis
just to have a check in with me and then I'll report back to their primary
pediatric rheumatologist or dermatologist.
Dr. Steph Dewar: So, Cassie, you mentioned that you did your training here and how you became
interested in scleroderma. I'm just wondering, was there something particular
about that disease process or rheumatology, in general, that sort of got you
going down this path?
Dr. C Torok: Yeah. So, on a personal note, back in high school I actually was on Minocycline
for acne, and this was before this was a known entity, but I had drug-induced
lupus. Had arthritis, the typical morning stiffness, swelling, et cetera, some
pericarditis, things of that nature. And, was seen by an adult rheumatologist and
actually, I remember my experience with an adult rheumatologist as a teenager.
This was back before pediatric rheumatologists were a little more common. I
then went to medical school at Hersey and ran into Barb Ostrov, and she's still
one of my mentors, and asked her, "Hey. Can I do an elective in pediatric
rheumatology?" She opened me up to the rotation. The first day, I fell in love
with it. I saw people with periodic fever syndrome, Raynaud's, pernio,
dermatomyositis, things I've never heard of, as a medical student, and knew
that that was for me. It was actually during my time with her where she was
presenting a case of atypical lupus that I kind of diagnosed myself, along with
her, that I had Minocycline-induced Lupus, in retrospect. So, that's how I got
interested in pediatric rheumatology and actually fast-tracked while I was here
and just did two years of general peds and then applied and went into the
fellowship right away.
Dr. J Williams: God, it's so fascinating how one's experience leads you to a field where, as you
mentioned, there are not a lot of pediatric rheumatologists, so the need is
great. But you didn't come to the field necessarily just because of the need
there, but because of your own experience. So, that's how you got clinically
interested in these diseases and taking care of these kids. How did you become
interested in doing the kinds of research you do on these diseases, which
include really basic laboratory techniques?
Dr. C Torok: Yeah. So, the research component came from wanting to understand some of
the biology behind it. We would see kids with very active disease. Typical
treatment is steroids or methotrexate and some would respond, a fair amount
do. But then, some would break through and keep having ongoing disease
which would cause further decrease in the size of the leg, or joint contractors, et
cetera. Trying to understand the biology, maybe other medicines that are
already available may work for these patients. That's why I work for biomarkers,
looking at biomarkers in the blood and in the skin during active disease versus
inactive disease, seeing if maybe a TNF-alpha, or something like that, is elevated
in active disease. Then, we could use drugs that are already available such as
Enbrel or Humira for this condition. We just haven't tried those yet, just because
those are kind of more standard for the juvenile arthritis. So, finding some
biology behind it to understand what drugs that are available now that might be
better treatments, but then also, opening the door for further research into
maybe newer molecules that haven't been identified that could potentially be
developed to treat this better.
Dr. Steph Dewar: So, you mentioned that some of the patients that come to you have been
misdiagnosed, or perhaps not treated. I'm just curious, are there common
themes behind the misdiagnoses?
Dr. C Torok: That's a great question. When I give some education conferences this is usually
what I talk about, how they present. Because it's important for the general
pediatrician providers to understand different ways it can show up. I've actually
had kids come from hematology clinic because they had this bruise that
wouldn't go away. Typically, a localized scleroderma, or also known as morphea
lesion, will start as, sometimes, an erythematous or violaceous linear band and
it may look like a bruise in the beginning. But, if it's a bruise and it's still there
after six months, and then it starts to get a little hard or turn a little brown,
usually that is starting to change into the linear scleroderma or morphea. So,
yes, it's the bruise that won't go away. I've had, also, kids have a smaller hand,
finger, the leg. They might go to neurology or genetics to try to figure out why is
the limb slightly smaller? But, unless you're actually feeling the skin or deep into
the fascia, you wouldn't realize that maybe they have deeper skin fascial or
muscle involvement from the linear scleroderma.
I've also had kids come with joint contractors because it goes from the skin
down into the tendons and ligaments. So, this is an inflammatory disease, it's
also fibrotic. So, the inflammation then leads to fibrosis or increase of collagen
deposition in the tendons, the fascia, et cetera. So, they might come to me with
a joint contractor. So, they may come from hand surgery because they have this
finger contractor, they can't open their fingers and they were told it was from
texting. But, if you actually feel all the way up the arm it may be some more
indurated areas up in the fascia of the forearm that's giving a pulley effect,
pulling down the fingers.
The other area to be knowledgeable is about new seizure in a child, just to kind
of screen and look for skin findings. The patients with linear scleroderma of the
head, about 20% can have some CNS or neurological issues. Sometimes, it's a
white matter lesion in the line of the area, sometimes it's uveitis or eye changes,
papilledema, et cetera. And then, there have been kids that have actually have
presented with seizures and then later, it was noticed, "Oh, they have a faint
erythematous linear band on their face." We've had a few patients that I've
shared with neurology that have presented that way. And, we're actually
working getting a publication to a pediatrics general journal to kind of get that
awareness out to neurologist, et cetera, who may be seeing these patients first.
Dr. Steph Dewar: So, I'm suspicious that earlier recognition, diagnosis, and treatment could
potentially affect outcome and debility.
Dr. C Torok: Yes, excellent point. The mean age of onset is around six to seven-years-old and
the mean time to a pediatric rheumatologist might be around eight to nineyears-old. So, there's about a two-year lag because of some of the issues I
mentioned. So, the more education and awareness we get out there, the better.
I had spoke at American Academy of Pediatric forums and also Grand Rounds, et
cetera. I'm actually going to a patient education conference in two days. So, I try
to get the word out with my colleagues as much as we can. There's only two
hundred pediatric rheumatologists in the nation, and there's just about four of
us that actually focus on this. So, that's why some of these things are
understandable that people aren't recognizing this, but we're trying to get that
Dr. Steph Dewar: So, to try and address the rarity, and what you mentioned, that the mechanisms
are not really well understood, you mentioned getting blood and skin samples
from patients. What do you do with those blood and skin samples in your lab?
And what are you learning?
Dr. C Torok: One main component that we're looking at is a composite biomarker. That
basically is, when the kids come in and they have active disease and floored. It's
very red, it's white waxy, it's erythematous. We can kind of tell that that's active
disease and typically we'll treat, and then they'll have the erythema, the
thickness will get better, just may be left with some trace hyperpigmentation, so
changes of the skin. But, then, usually, it's pretty quiet. But then, 50% of these
patients recur. When they flare, it's unclear. They might just have a little bit of
pink or red color change, or a little bit of itching of the skin. But, right now, even
us experts, it's hard for us to tell when exactly the flare is starting, so when to
restart this methotrexate, or the steroids, et cetera. So, what my main focus is,
is developing a blood biomarker that will help with your clinical assessment of,
"Hey. Is this patient active again? When do we start treatment?"
So, I'm trying to use the patients that have clear cut and active disease, no
treatment, store their blood and get their skin samples. I follow these patients
longitudinally, treat them, get them when they're inactive, collect that blood
and skin and then compare the two. So, then you can define the biomarkers
that are definitely elevated and predominate in the active phase of disease. So,
then you can use it later to help then predict, in general, other patients, how
active their disease is if you should restart therapy. So, it's a composite of the
serological biomarkers like cytokines, ketokines. We've seen CXCL9, CXCL10,
other interferon gamma-associated biomarkers. Then, also, in the peripheral
blood looking at the cellular markers, doing flow cytometry and CyTOF, which is
just fancy flow cytometry using metal tagged ions. Then, also, looking at, in
tandem, the skin. And, again, doing similar methodology, we're looking at flow
cytometry, et cetera. But then, we're also doing RNA SIQ, which is looking at the
transcriptome expression. And then, also, single-cell sequencing.
So, we actually can tell what cells are kind of driving these biomarkers. For
example, I mentioned CXCL9 and 10 in the peripheral blood, but actually, when
we do RNA single-cell Seq and look at what cells are actually different in the
localized scleroderma patients from healthies, and also compared to
active/inactive, the fibroblasts that have CXCL9 and 10, are actually different in
pediatric localized scleroderma compared to pediatric healthy control. So,
things like that may help say, "Oh, these biomarkers are of interest. One, the
can help tell us if the disease is active or inactive.", or, maybe prognostic
biomarkers. "Hey. This kid's going to flare down the road or have more severe
disease." And also, may help for therapeutic drug targets as well.
Dr. Steph Dewar: So, this sounds like research which is very patient-based, not an animal model
to help you with this
Dr. C Torok: Correct.
Dr. Steph Dewar: ... in a very unusual disorder. So, it sounds like there might be a challenge
getting adequate numbers. I'm wondering what other barriers you have to your
work, like patient access. I'm just wondering if there's innovations that you have
thought about or have used to help improve patients access to you.
Dr. C Torok: Yes. So, as far as patient access, I work with my social worker and we do help fly
patients and provide some funding and housing there, and actually, I help
connect patients. So, if I know it says "teenage female of this age" and she has
linear of her leg and is maybe having trouble, then I will try to help connect
them, as far as both parties agree, to other children with this and also for their
parents to help. Being at the patient education conferences, I've had a ton of
one-on-one time with patients and families that may not be able to physically
make it here at Pittsburgh, but I'm always at the Scleroderma Annual Patient
Education conferences, so they know where to find me. Then, we just develop
this Kids Get Scleroderma Too, patient education conferences. The second one
we're having in two days in Colorado. So, I'll be out there and meeting up with
patients that may not have access to me for whatever travel reasons, et cetera. I
do try to make myself accessible other ways, and that's on the clinical basis.
On the research basis, I actually am the central biorepository and lead some of
the multi-center studies that I have available through CARRA. So, CARRA is
Childhood Arthritis Rheumatology Research Alliance. Why that exists is not just
pediatric scleroderma, but pediatric juvenile dermatomyositis, pediatric lupus,
pediatric juvenile arthritis. All of these are relatively uncommon conditions, so
we need to work together at the different sites so that we have the numbers to
do research. Clinical research, translational research, et cetera. Therefore, I'm
one of the leaders of the pediatric scleroderma group, so what I've done is, I've
developed, with some of my colleagues, such as Susan Lee at Hackensack, New
Jersey, protocol where they enroll into the registry, we collect the clinical
research data, the variables, et cetera from these multiple centers, and then I'm
the biorepository, so they'll collect blood and ship it over. So, even if I physically
can't see the patient, they're seeing another peds rheumatologist who's
invested enough to collect the clinical data, the collect the blood and send it and
be part of these multi-center studies.
Dr. J Williams: So, it's really critical, clearly, for these uncommon diseases of childhood to have
these networks and groups of other physicians, and families, and patients who
are dedicated enough to do what it takes to advance the field and develop new
tools and new treatments.
Dr. C Torok: Correct. So, having the physicians onboard and collaborating, but then, also the
patients and different patient advocacy through, as I mentioned, sometimes it's
the Scleroderma Foundation, I have patients that they have a Facebook like
Sclera Moms, but it's a private Facebook, so you have to get invited. But, they've
networked themselves and then, some of them will see me and they'll say, "Oh.
You need to see Dr. Torok." So, not to my doing, but they communicate as well.
So, yes, it's both the patients and the clinicians kind of working together.
Dr. J Williams: Steph touched on this. For this disease, it sounds like this is the only way you're
going to move the field forward. There's not any kind of small animal/mouse
model or anything that people can study. Is there?
Dr. C Torok: We're starting to collaborate. One of the Ph.D.'s at Boston, so, Gillian Richmond,
we just wrote an R1, so we'll see where it goes. But, they are looking at,
traditionally, systemic scleroderma is more common in the adult field and I do
have systemic scleroderma patients and do research on that as well, but
localized is way more common. But, we've used the bleomycin mouse, which is
typically a fibrosis mouse that the adult systemic scleroderma researchers use.
But, basically, taking it just a day or two into the bleomycin process before the
fibrosis gets too far in the skin or the lungs, is actually or kind of morphea model
or localized scleroderma model. So, we've kind of just used that mouse model
but just slightly adjusted it and we're starting to find skin changes and when we
do the biopsy of the mouse skin it looks similar to the human localized
scleroderma skin. Right now, actually, we're doing the RNA Seq and the Bulk Seq
and the single-cell Seq to see if it's similar or not to our localized scleroderma
patients. So, that's happening right now. Most likely, mouse model. But, we're
working with it right now, but that's new.
Dr. Steph Dewar: So, you mentioned previously that you also have done some work with
neurologists with the finding about the symptom of seizures in some patients
with scleroderma. Are there other subspecialty collaborators that you have in
Dr. C Torok: Yeah. So, I've been working a little while with Dr. Losee here at Children's
Hospital Pittsburgh. Especially for the patients that have the linear facial
involvement. We call it our linear scleroderma of the head/Parry–Romberg
clinic. But, basically, linear scleroderma of the head can be sub-termed, en coup
de sabre, or French for "sort of the saber" because it looks like a linear line or
depression on the face/skull with some alopecia, et cetera. Or, it can also be
termed Parry-Romberg, which is hemifacial atrophy, so one side of the face is
In reality, these kind of overlap. They have similar phenotypes. I have children
that have en coup de sabre on the left, and Parry-Romberg on the right. So,
they're kind of all in the same boat. But, we see these patients in tandem
together, usually on a Monday when he has his craniofacial clinic that the dental
orthodontics come in as well as the craniofacial plastic surgery. We do 3D
imaging of the face and then we monitor the child at the next visit, we do 3D
modeling again with the camera, and we kind of overlay those pictures and if
there's progression of the disease, there's a color, it will look kind of red or
depressed, then we'll know, "Okay. This is depressed disease." Then, on the
other management side, Dr. Losee also collaborates with myself and then Jessie
Goldstein as well, to treat these patients after the therapies we mentioned like
steroids, or methotrexate or CellCept and other medicine. If they're in remission
and the child is unhappy with the depression on their face, et cetera, we do fat
grafting. So, basically, taking some of the fat, spinning it down, and do micro-fat
grafting to kind of even out the face. So, we have kind of a team here.
Dr. J Williams: Well, it's really an incredible multidisciplinary effort. Isn't it? Both in the clinical
side and in the research realm. It just shows, I think for something as complex as
this, that you need so many different people with different expertise to attack
it. Maybe in the last couple minutes, you could just tell us a little. You're
engaged in so many different things from directly seeing patients, to clinical
research, to lab research, being a physician-scientist and balancing those things
and how you enjoy that.
Dr. C Torok: I mean, I love what I do. I just took that UPMC survey about your quality of life. I
love what I do, I love my colleagues, all my colleagues are supportive, so I haveDr. J Williams: That was not a sponsored statement, by the way.
Dr. C Torok: I have clinicians in my group and we work together. So, if things are stressful
and someone needs to see someone in clinic, they'll say, "Hey. I'll see that
patient. I know you have to go run up to the lab." So, I think it also depends on
the balance in your group and how supportive your group of colleagues is. So,
my group of colleagues is very supportive and also, I mentor a lot of people. So,
they also understand the projects and research that I do with my fellows, et
cetera. So, I would say it's a balance. I don't get much sleep, that's the reality of
it, but I'm happy. I think, basically, in pediatric rheumatology, some of these kids
can come in very sick, but we have advanced medications and more research
keeps coming. There's more biologics that keep coming down the road, that it's
very gratifying because we can help these patients and treat them. And,
hopefully, one day, actually find a cure. Maybe good or bad, then I won't have a
job. But, hopefully, find a cure.
So, I think, the bottom line is, yes, I juggle a lot, but I also have great colleagues
that help balance the clinical and research part as well as excellent fellows and
other people on projects that are kind of doing their own thing, but I'm
mentoring, so we can still keep the research moving forward, it just might be
more of their ideas. I also do things with quality of life, I do a little bit of
everything. So, I think, basically, just working as a team, getting collaborators,
sharing those projects. I didn't mention, with the biorepository, it's not just my
research, I have a ton of colleagues that say, "Hey. I have this idea. This IL12 in
this disease. I want to see if it's in pediatric localized scleroderma." I collaborate
with people all the time because this is a national registry meant to collaborate
Dr. Steph Dewar: Well, Cassie, I really appreciate you joining us today. Certainly, I have always
found your support to be a breath of fresh air. Incredibly knowledgeable
clinician with some of the more challenging patients that we've run by you. I
want to thank you for joining us on the podcast today.
Dr. J Williams: Yeah. Thanks to our guest, Dr. Cassie Torok, physician-scientist and director of
the pediatric scleroderma clinic. We'll see you next time on That's Pediatrics.
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