When a child is diagnosed with a rare and complex disease like scleroderma, families experience a lot of stress and often feel like they are completely alone.

You are never alone. That is why we will dedicate several episodes of The CARRA Podcast to exploring different diseases that make up our CARRA community. We will talk to pediatric rheumatologists about the basics of each disease, the latest updates in research, where future research is heading, and how families can get involved in supporting research.

This episode focuses on scleroderma, a disease that the host of the CARRA Podcast was diagnosed with at nine years old. Our guest is scleroderma expert Dr. Kathryn Torok, a board-certified pediatric rheumatologist who is the director of the Pediatric Scleroderma Clinic at UPMC Children’s Hospital of Pittsburgh and the co-director of the Pediatric Craniofacial Scleroderma Clinic. 

Dr. Torok, who co-leads CARRA’s Scleroderma Workgroup, explains the different types of scleroderma, explores the challenges that patients and physicians face, and shares the latest exciting updates in her scleroderma research.

In non-doctor speak, can you explain to me what scleroderma is?

Scleroderma is hard to say, so it’s okay if you’re not saying it correctly 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 means hard skin. It is an umbrella term that we use for both forms of scleroderma.

There are two main types: Systemic scleroderma, which affects larger areas of the skin, many areas of the body and has some internal organ damage and localized scleroderma (morphea), which typically appears in bands on the skin, maybe down the arm, the center of the body or the head or face. “Sclero” (hard) – “derma” (skin) is a feature in both forms of the condition, so that’s why it gets its name.

They’re both autoimmune diseases, 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, when 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.

I want to talk through these two different types a bit – localized and systemic scleroderma – and how their experiences may differ from one another. Can you tell us about that?

Sure, I’m going to focus on pediatric scleroderma, so it’s slightly different than what the adult scleroderma patients experience. Localized scleroderma is more common in children and often manifests as skin discoloration or thickening in bands, usually on the limbs or face. It can affect mobility, especially if it crosses joints. Systemic scleroderma, while less common in children, affects internal organs like the GI tract and can cause issues like Raynaud’s phenomenon, and growth problems due to poor nutrient absorption.

What are the initial symptoms parents might notice in children with 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 who are two to three years old. For localized scleroderma, parents might notice divot in the skin or discoloration or a bruise-like appearance that doesn’t fade. As it progresses, it can go into the tendons, ligaments, and muscles, and it can cause a limitation or range of motion of your joints, you know, such as your finger or wrist.

Kids are very 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 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.

For kids with systemic scleroderma, it’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 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.

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

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?

Usually, they are seen by their pediatrician and the pediatrician tends to refer those patients with a linear scleroderma, say linear scleroderma on the arm, for example, to dermatology. I would suggest that they try to see pediatric dermatologist. That’s kind of the first step, and then 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 we also assess for different things. There are 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.

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. If there was like linear involvement of the head, there may be an ophthalmologist and other specialists involved. Usually, the rheumatologist is the ringleader that pulls in the different therapists and different specialists.

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

Start with your pediatrician. If you happen to be near an academic center that has a pediatric rheumatologist, usually they may 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. 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.

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

This is a bit more involved. The main feature would be the Raynaud’s, and Raynaud’s is prevalent in about maybe 10 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.

The pediatric rheumatologist at that point is definitely the main person, and they will need to make the official diagnosis. Systemic sclerosis is a little trickier diagnose 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 scleroderma, maybe even features of our other diseases like lupus or myositis, but not fully meeting criteria. So, more evaluation is needed. 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.

Regarding treatment, what do you see as the biggest barrier facing scleroderma kids, localized or systemic?

In pediatric rheumatology, whether we’re talking about scleroderma or pediatric lupus or pediatric dermatomyositis, there’s really not any or many FDA-approved 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 we want to use if they have more muscle involvement, 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. There are always lots of phone calls between the nurses, the doctors, and we send in whatever publications we can, but 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. This is because it’s a rare disease. You’ll see this in many pediatric rare diseases.

Now for juvenile arthritis, 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 our biggest barrier is getting the drug actually to the patient in an affordable way.

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. Would you consider that to be a common misconception impacting pediatric scleroderma patients?

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. 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 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 the tissue, like the muscle. And in the end, if untreated, 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.

In terms of scleroderma research, what is the most exciting new development for you?

There are lots of things that are exciting. For localized scleroderma, we have a craniofacial scleroderma center, so when patients see me, they also see my craniofacial plastic surgeon, an ophthalmologist, a dentist, an 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.

With that center, we also have 3D facial imaging using handheld cameras. 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. 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 only kind of NIH clinical trial for juvenile systemic scleroderma, and that’s just life changing.

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.
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 been altered or changed. 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.

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?

Patient engagement in research is key. I couldn’t talk to you about these research outcomes and studies without patient engagement and involvement. 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 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. 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, and any quality-of-life measure that you may have. 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. Then I could see the average age is four. So, there’s so many interesting things that you can answer or start to answer with a registry.

At CARRA, the one observational cohort study that we recently had was SCORE. That was the one that focused on 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.

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?

Sure, so I wear multiple hats as a clinician and a researcher. What helps is that when you live in both worlds like this, you can definitely answer questions that are called like bench to bedside or nowadays it’s actually bedside to bench.

What I mean by bedside to bench is I’ll notice something clinically like the example I just said, where I notice that my craniofacial scleroderma patients that seem to be very young and they seem a little bit younger than my kids with a linear scleroderma on their arm. So, I think, 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 can think about scientifically what way you might answer that question.

We actually have a grant right now through the National Scleroderma Foundation with Dr. Deepa Rajan asking that exact question. She’s a neuro-geneticist here at Children’s Hospital of Pittsburgh. The question is: Why are they so 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 a somatic variant or somatic mutation, meaning something you’re not necessarily born with, but it happens in a certain group or line of cells during development. We’re trying to see if there’s some somatic variant or mutation there in those children.

This episode was edited by Mason Lippman.

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About Kathryn Torok, MD

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