Pediatric Scleroderma with Dr. Kathryn Torok

This episode focuses on scleroderma, a disease that the host of the CARRA Podcast was diagnosed with at nine years old. To help explain what the disease is all about, we turn to Dr. Kathryn Torok, Associate Professor of Pediatrics and Clinical and Translational Science. Dr. Torok is the director of the Pediatric Scleroderma Clinic at UPMC Children's Hospital of Pittsburgh, where she is also the co-director of the Pediatric Craniofacial Scleroderma Clinic. 

Dr. Torok explains the different types of scleroderma and how doctors diagnose them, as well as the possible treatment options and the challenges that patients and physicians face with this rare disease. As a leading researcher in pediatric scleroderma who co-leads CARRA's Scleroderma Workgroup, Dr. Torok also shares the latest exciting updates in her scleroderma research.

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Pediatric Scleroderma with Dr. Kathryn Torok

Claudette Johnson: CARRA, the Childhood Arthritis and Rheumatology Research Alliance, represents dozens of different diseases, different experiences – all that begin with a diagnosis. There is stress in the new diagnosis period, especially with rare diseases where you feel like you're completely alone.

You are never alone. That is why we will dedicate several episodes to exploring different [00:01:00] diseases that make up our CARRA community. How to get a diagnosis, the basics of the disease, where research is heading, and how you can help. You're listening to The CARRA Podcast. My name is Claudette Johnson, and I'm your host.

Claudette Johnson: Today, scleroderma, a disease that I was diagnosed with at nine years old. To help explain what the disease is all about, we turn to Dr. Torok, Associate Professor of Pediatrics and Clinical and Translational Science. She is the director of the Pediatric Scleroderma Clinic at UPMC Children's Hospital of Pittsburgh, where she is also the co-director of the Pediatric Craniofacial Scleroderma Clinic. Dr. Torok, thank you so much for joining us.

Dr. Kathryn Torok: My pleasure. Glad to be here, Claudette. 

Claudette Johnson: So, here's the first challenge. In non-doctor speak, can you explain to me what scleroderma is? 

Dr. Kathryn Torok: Sure. Scleroderma is hard to [00:02:00] say, so it's okay if you're not saying it correctly in general when you're visiting with your healthcare provider. It actually has a Greek background, “sclero” meaning sclerosis or hardened, and “derma” means skin. So, scleroderma, hard skin, that's the origination of the term. That is an umbrella term that we use for both forms of scleroderma that I'm sure we'll get into during this discussion, but just to give the two names.

One is systemic scleroderma, or systemic sclerosis, and that's where that hardened skin that comes from the root of the name. That's usually throughout many areas of the skin, many areas of the body and has some internal organ damage. systems that go along with that localized scleroderma or morphia is the other term that also is in this umbrella of scleroderma.

We call it localized because it tends to go in bands, maybe down the arm, the center of the body or the head or face. [00:03:00] And that's why it's called localized scleroderma, but that “Sclero” (hard) – “derma” (skin) is a feature in both forms of the condition. So that's why it gets its name and they're both autoimmune disease, meaning the immune system is overactive and starts attacking itself.

So, if somebody did a biopsy of the skin in either the systemic scleroderma or the localized scleroderma forms, they look under the microscope and they would see extra immune cells that shouldn't be there in the skin. So that's kind of the driving force of this condition, it's autoimmune. You're not born with it; it's bad luck. The immune system just went a little haywire, and it needs to be regulated typically with some of our medications we use in rheumatology.

Claudette Johnson: I just want to talk through these two different types a bit – localized and systemic scleroderma – and how their experiences may differ from one another for the patients. 

Dr. Kathryn Torok: Sure, I'm going to focus on pediatric scleroderma, so it's slightly [00:04:00] different than what the adult scleroderma patients experience. So, from a pediatric scleroderma standpoint, localized scleroderma, (or morphea) is the other term, is much more common in pediatrics. So, we see localized scleroderma much more common than systemic scleroderma. So, for localized scleroderma in kiddos, usually the onset of disease is around six to eight years old on average, but there's definitely some younger children, you know, two to three years old.

Dr. Kathryn Torok: The children usually don't have too many outward symptoms. As far as pain or limitation at first, you know, it might be a discoloration of the skin. The skin has a divot or may look like a bruise that won't go away. But then over time, it does tend to get deeper, especially if it's crossing the joint. And then it can go into the tendons, ligaments, and muscles, and it can cause a limitation. of the range of motion of your joints, you know, such as your finger or wrist. And the kids are [00:05:00] resilient. They're really most of the time not going to say anything. It's just the parents pick up and say, “Hey, why is little Sally not able to draw anymore?”or, “She's holding this funny or she can't open this jar or something like she used to.” So that's typically how a localized scleroderma patient might present. There are various forms of it, but that's just kind of the generic kind of linear extremity localized scleroderma presentation.

And sometimes if it's the lower extremity, it might be limping or something like that. They might go to orthopedics or neurology or something before they get the final diagnosis from a dermatologist or rheumatologist. 

Dr. Kathryn Torok: For kids with systemic scleroderma, that's a little bit different.

It's a systemic disease, so a lot of the times it might be very subtle at first. It might be fatigue that's kind of unexplained and failure to thrive, which means like poor weight gain. It's unclear, but for some reason, the child on the growth curve is just not gaining [00:06:00] weight or height. And then you kind of dig deeper and they're just not hungry. They don't have an appetite. And that's usually because they have some esophageal or GI dysfunction, and they're just not hungry because they're, you know, their stomach doesn't feel good. Then the Raynaud's is that kind of color change and numbness and tingling of the fingers and toes. That typically will happen around that same time at the beginning.

And that can be very distressing because watching your child's fingers turn kind of purple and then white. And then they have trouble opening things when that's happening. Those are usually kind of the onset of symptoms that the other organ manifestations typically are figured out by the doctor doing different investigations. But those are the main, main two examples I can think of how children might have initial symptoms at their onset. 

Claudette Johnson: I envisioned a parent who searched up this episode because their child has just been diagnosed with typical localized scleroderma. Where would you recommend that they start? 

Dr. Kathryn Torok: Usually, [00:07:00] they are seen by their pediatrician and the pediatrician tends to refer those patients with a linear, say linear scleroderma on the arm, for example, typically would refer to dermatology. I would suggest that if they haven't, they see pediatric dermatology, they just see it more often and might be more in an academic center. And that's kind of the first step. I would definitely want to make sure that child was also referred to a pediatric rheumatologist, just because we work in tandem with dermatology, but kind of also, assess for different things.

Dr. Kathryn Torok: There's some things in the blood work we might be looking for. Also, the exam, the disease seems potentially to be a little deeper. We might do an MRI or ultrasound to look at the tendons and ligaments and joints, things of that nature. 

We're a little bit more similar these days. There are more publications coming out dermatology side of using the [00:08:00] immunomodulators such as methotrexate and mycophenolate mofetil and steroids, but that's a little bit more in the pediatric rheumatology wheelhouse. So, the treatment styles are a little bit different.

I would encourage that they do get referred to a pediatric rheumatologist. And then usually it's like a co-management style. Then beyond that, the pediatric rheumatologist may recommend other multidisciplinary care. 

For example, if the patient has a limitation range of motion of their hand, they might get occupational therapy involved.That's especially important at the beginning of the disease to make sure they don't lose range of motion. And then if there was like linear involvement of the head, there may be an ophthalmologist and other specialists involved. Usually, the rheumatologist is kind of like the ringleader that pulls in the different therapists and different specialists to help co-manage that pediatric patient.

Claudette Johnson: How do you find a pediatric rheumatologist and how do parents find someone like you? 

Dr. Kathryn Torok: Number one, start [00:09:00] off with your pediatrician. They're following you anyway. If you happen to be near an academic center that has a pediatric rheumatologist, usually they're gonna sometimes even know that person personally and call them up and say, “Hey, I have a patient to refer,” and that might get you in a little sooner.

If that's not the case and you live far, far away from a pediatric rheumatologist, I would suggest the Scleroderma Foundation website. We do have different scleroderma centers that are recommended, and most major children's medical hospitals will have some pediatric rheumatologists. And then if you want to go to a scleroderma expert, there would be a little bit more information on the Scleroderma Foundation's website about finding one.

Claudette Johnson: Now, talking about a typical systemic sclerosis patient, what would you say are the first steps that they should be taking? 

Dr. Kathryn Torok: The main feature would be the Raynaud's, and Raynaud's is prevalent in about maybe 10 [00:10:00] percent of the healthy population. So, it's not Raynaud's alone, but it's Raynaud's in context of not gaining weight, especially like digital ulcers, like little ulcers on the tips of the fingers and skin changes, skin thickening, you know, that would definitely prompt more investigation. And if the pediatrician that is getting concerned, I would definitely make sure getting to a pediatric rheumatologist is the next step.

This is a little more involved. The pediatric rheumatologist at that point is definitely the main person. Dermatology, not as much, you know, they might be one of the many specialists or consultants, but it's usually the rheumatologist. That's kind of the ringleader at that point, they will need to make the official diagnosis.

It's a little more tricky to be honest. There's certain criteria and things that we look for because sometimes it's not straight up systemic scleroderma. Sometimes it's early connective tissue disease. We call undifferentiated connective tissue disease where they might have features of [00:11:00] scleroderma, maybe even features of our other diseases like lupus or myositis, but not fully meeting criteria.

So, more evaluation is needed. And so the pediatric rheumatologist has to A) Be the one to really diagnose the patient and then B) do further evaluation. And that requires a series of things such as like echocardiogram, pulmonary function tests, checking out organs, you know, heart, lungs, and then getting this and then there's certain subspecialists that are associated with that involved as well.

Dr. Kathryn Torok: So, that is a little more involved, but the pediatric rheumatology is the first stop. And then they help maneuver and guide the patient through the other healthcare providers. 

Claudette Johnson: And regarding treatment, what do you see as the biggest barrier facing scleroderma kids, localized or systemic? 

Dr. Kathryn Torok: In pediatric rheumatology, whether we're talking about scleroderma or pediatric lupus or pediatric dermatomyositis, there's really not any or many FDA approved [00:12:00] medications. So that is our biggest barrier. We actually go in knowing what we want to treat the patient with. We have a list of medications where we say, okay, they have more muscle involvement, they have more joint involvement, or they have more skin involvement, or they have a combination of these things.

So, we go in having an idea of what medication we feel is probably best for the patient. But if it's not FDA-approved and it's not on their particular insurance’s list of FDA-approved medications, getting insurance authorization is a huge barrier. You know, there are lots of phone calls between the nurses, the doctors, and we send in whatever publications we can, and then whether they approve it, it's sometimes it's just kind of the flip of the coin, unfortunately. So that is our biggest barrier, the insurance company not approving the medication, which ties a little bit back to FDA approving the medication, which goes back to not having clinical trials in that to get that FDA approval. So that's kind of where [00:13:00] it comes from, but that's because it's a rare disease. You'll see that in many pediatric rare diseases.

Dr. Kathryn Torok: Now for juvenile arthritis, which is, kind of the hub of what most pediatric rheumatologists treat, there are actually clinical trials and studies and FDA approvals. So, we try to piggyback on that and say, “Hey, this medication is FDA approved for kids with juvenile arthritis in ages 2 to 18. It's safe. Can we then get this approved for this individual patient with scleroderma?” So, that's sometimes how we'll kind of work with that. But that's our biggest barrier is getting the drug actually to the patient in an affordable way.

Claudette Johnson: Okay, I want to just talk a little bit here about when I was diagnosed. It was caught early, which was amazing, but I was told that it didn't require any treatment. [00:14:00] Would you consider that to be a common misconception impacting pediatric scleroderma patients? 

Dr. Kathryn Torok: Yes, sadly, that is, in my mind, an old wives’ tale. You still see that in some of the dermatology literature that it will just “burn out.” It's really upsetting to our community at large, especially the pediatric rheumatologists that are scleroderma experts. I still see that in some of the manuscripts submitted to journals and some people will say that. What a shame is that. It has changed over time. That was once a common thought that in five to 10 years, it will burn out. But what's really happening is the immune system is activating connective tissue in the skin, like fibroblasts and other things. And they're starting to lay down some extra collagen.

It makes the skin thick, and it also kind of makes the skin thin and the fat thin and then can go deeper into the different layers of [00:15:00] the tissue, like the muscle. And in the end, if you just let it do its thing, you might end up with a giant indent on the young person's leg or a limitation of their joint range of motion and a leg discrepancy, so they have a limp, and that's the rest of their life. You only have one body.

Dr. Kathryn Torok: So now we know that there was a clinical trial – like the only randomized clinical trial – back in Italy was back in 2016 or so. Dr. Francesco Zulian did show that methotrexate versus placebo definitely showed a difference. The patients responded, both had some steroids in the beginning, so they both responded, but then after three months of steroids, they stopped and just gave them placebo, which is fake medicine, and then the other arm got methotrexate.

The arm that got placebo, 75% of them flared the disease, came back and caused more damage. Whereas the patients that were on the methotrexate, they remained in remission and didn't have more damage of the skin and the underlying tissue. [00:16:00] So that was like a landmark study. So since then, people should recognize that are immunomodulary medicines like methotrexate and mycophenolate mofetil and steroids, they do actually halt the disease.

And not just spreading on the surface, but they stop the spreading deeper and into new areas. So, we do highly recommend these types of therapies, especially if it crosses the joint, if it's on the face or the scalp, it has changed. I don't think anyone really recommends kind of letting it burn out. So hopefully that message is made clearer these days.

And if you hear that and you're a new patient, I would encourage you to go to, if that was a dermatologist, to consider going to an academic pediatric dermatologist or a pediatric rheumatologist just to get a second opinion. 

Claudette Johnson: Speaking of new research for scleroderma, what is the most exciting new development or new thing for you?

Dr. Kathryn Torok: Oh, there are lots of things that are exciting. For localized scleroderma, we have a [00:17:00] craniofacial scleroderma center, so patients that come and see me, they see me as a pediatric rheumatologist, they see my craniofacial plastic surgeon, they see an ophthalmologist, they see a dentist, orthodontist, and then I have a neurologist and a neuro-geneticist to see if there's some brain changes.

We also have a neurologist that reviews their brain imaging. So by having a comprehensive center like this, we're starting to see more and more things kind of that we weren't necessarily aware of coming to the surface and then seeing if different treatment might change the trajectory of these patients. This is still in the making, but there's definitely more research coming and we have published this: About 35 percent of patients that have linear scleroderma of the head do have some kind of brain changes. Some are mild, but they should be acknowledged and followed. This wasn't really kind of known and it was not known how frequent that is. Also, there have been some patients [00:18:00] that we have demonstrated with certain treatments to respond and those lesions or areas that were abnormal kind of changed, so that's kind of newer. 

Dr. Kathryn Torok: With that center, we also have 3D facial imaging. So we use cameras, they're handheld, it's really nice, they're easy, where we take pictures, the camera stitches it together with the software, and you get a 3D shell of the patient's face. Then you can get another picture at their follow-up visit six months or a year later, overlay them, and that can give you a little more concrete evidence of did the area get more depressed or not. If they had fat grafting with our craniofacial plastic surgeons, we can see if the fat grafting, you know, kind of stayed, and if so, how much volume. So, the 3d imaging is really exciting. And we actually just submitted a manuscript that hopefully comes out soon. 

In the systemic scleroderma world, we are doing stem cell transplant here at University of Pittsburgh. We have, I believe, the nation's [00:19:00] only kind of NIH clinical trial for juvenile systemic scleroderma, and that's just life changing.

I mean, we've transplanted seven patients thus far, and these are patients who are bedridden, some of them, and go from, basically taking two adults to get them up and really out of the bed to them being independent. And I just saw one of my patients just literally get right off of her wheelchair and just like pop on up and start to do some more PT and independent exercises.

So that's our goal to get these patients like to independence and kind of reset their immune system. It's intensive, it involves chemotherapy and kind of resetting the immune system, but it's been remarkable. That's the most rewarding I would say. And I'm still doing lots of research on that.

 I'm doing biopsies of the skin before and after and different blood markers before and after. So we're trying to see, you know, what in the immune system was going wrong before the stem cell and what has [00:20:00] been altered or changed. We're trying to get more information there as well. So, that's a really exciting project.  I could talk about 40 other projects that we have going on nationally and internationally, but those are the two that I would highlight.

Claudette Johnson: That all sounds so amazing. So, going back into the whole idea of research, we've done an episode on registries and their importance, but for you as a researcher, can you talk a bit about how big of a deal it is for you guys to have patients participate in research and what sort of an impact that can have?

Dr. Kathryn Torok: So, I mean, patient engagement and research is key, right? I couldn't talk to you about these research outcomes and studies without patient engagement and involvement. So registries are the best way and honestly the easiest and most non-invasive way to help research move forward in any pediatric rare disease.

What an observational cohort study is literally when you go to the doctor, you're just giving them permission to [00:21:00] de-identify you, meaning like your number 678 in their database and you will always be 678, but it doesn't have your name or anything like that. And it associates the clinical data that was collected that day from clinic or the clinical research forms, like the skin score, the joint limitation, range of motion, things like that. And any quality-of-life measure that you may have. Part of that registry to see how it affects you on a day-to-day basis. And then kind of putting that in together. So, when we pull the data, I can say, “Hey, what's the average age of onset in pediatric localized scleroderma affecting the face?”

Then I can pull that data from a cohort of, you know, out of 700, a cohort of maybe 120, 140 would have craniofacial scleroderma. And then I could get, Oh, the average age is four. So, there's some interesting things that you can just answer or start to answer questions just by joining a registry.

Dr. Kathryn Torok: It's really minimum [00:22:00] work for the patient. It's some couple quality of life forms and it has no impact, zero impact on your clinical care. So, if you join the registry or not, does not impact whether your doctor prescribes this medicine versus that medicine. It's not a clinical trial. It's literally just a registry.

Dr. Kathryn Torok: It’s getting a couple tubes of blood that gets sent and then my lab typically will process it and store it. We're trying to make it non-intrusive to their everyday life. So, like, again, minimal work on the patient's side of things. That's an observational cohort study.

At CARRA, the one that we recently had was SCORE. That was the one that focused on [00:23:00] localized and systemic scleroderma. We're hoping to like revamp and kick that up and open it up the general care registry to more pediatric scleroderma patients as well. 

Claudette Johnson: As we've said, you're a doctor who has tons of patients and you're greatly involved in research. Could you just talk a little bit about how does working with patients inform your research and vice versa? 

Dr. Kathryn Torok: Sure. So, I wear multiple hats: One obviously is the clinician's hat, one's the researcher hat. What helps is that if you kind of live in both worlds, you can definitely answer questions that are called like bench to bedside or nowadays it's actually bedside to bench.

And what I mean by bedside to bench is I'll notice something clinically like the example I just said, I'm like, huh, I'm craniofacial scleroderma patients that seem to be young. Seems a little bit younger than my kids with a linear scleroderma on their arm. Let me go in the registry and just take a look. And then you can kind of look at the averages of onset.

And then you can say, is there, is there a reason for that? And then you [00:24:00] can think about scientifically what way you might answer that question. And we actually have a grant right now through the National Scleroderma Foundation with Deepa Rajan asking that exact question. She's a neurogeneticist here at Children's Hospital of Pittsburgh.The question is, Why are they young, and why is it happening in a particular band? So, we are taking a biopsy of the affected skin and the unaffected skin of the face scalp area of these patients. We're sequencing to see if there's like a role in what's a somatic variant or somatic mutation is, is meaning something you're not necessarily born with, but it, it happens in a certain group or line of cells during development. So that's what we're trying to see if there's some somatic variant or mutation there.

And why we're doing that is because when you see these kiddos with the linear band on their forehead for say, and they have a change [00:25:00] in their brain, it's usually like in that same exact plane. So, that to us is like maybe some, something that shared developmentally in those tissues versus like issues that aren't affected. So that's a prime example of some question that I had by seeing kids over and over again and seeing kind of like their skin changes and their brain changes. Something's a little different and they're a little younger. We're kind of actually sequencing and answering that question right now. So that's like the bedside to bench opportunity that we have by seeing the patients.

And then having that observational cohort with these samples banked up to be able to answer those questions. Right. It's a little hard if you're kind of capturing clinical data all this time, but not getting the blood or the skin with it. So that's a little lecture layer. 

Dr. Kathryn Torok: If the patients are approached, I would encourage you to say yes to it because it really does help. We're going to see how we can, how we can help us move the field forward. And if we have questions, we can go back to that banked specimen that matches your clinical data.

Claudette Johnson: Dr. Torok, it has been such a pleasure speaking with you. Thank you so much for all you do and for joining us today. 

Dr. Kathryn Torok: Surely, of course. My pleasure. 

Claudette Johnson: CARRA is the Childhood Arthritis and Rheumatology Research Alliance. We are doctors, researchers, and patients all working together to prevent, treat, and cure pediatric rheumatic disease.

And we want to hear from you. If you have a topic for an upcoming episode, head over to our podcast page on the CARRA website and leave us a message through a SpeakPipe link. We might play your voice on a future show, and we'll do our best to answer your questions. Finally, we encourage you to share the CARRA podcast with friends, patients, and anyone else interested in learning more about the incredible work of the CARE community, dedicated to creating a world free of limitations for children with rheumatic disease.

This episode was produced and edited by Mason Lippman. Our [00:27:00] music is by Jonathan M. Horner. Thank you for listening.