Serious Eczema Symptoms Beyond the Skin with Jonathan Silverberg, MD, PhD, MPH

Erin Spain: This is Breakthroughs a podcast from Northwestern University Feinberg School of Medicine. I'm Erin Spain, Executive Editor of the Breakthroughs Newsletter. The health issues facing people with severe eczema are not only skin deep. Aside from the intense itching and dry irritable skin, many people with a type of eczema known as atopic dermatitis also have significantly higher rates of medical and mental health issues. Dr. Jonathan Silverberg studies eczema and treats some of the toughest cases at Northwestern Medicine's multidisciplinary eczema center. He's an associate professor of dermatology at Northwestern and has just published a new study in the British Journal of Dermatology that shows half of all adults with eczema experience, anxiety or depression. Why does the skin condition come with so many other health issues and what can be done to give patients relief? Dr. Silverberg is here to share some insight. Thanks so much for being here today.

Jonathan Silverberg: It's great to be here.

Erin Spain: So many people think of eczema as a childhood condition and it often does start in childhood, but this is an adult disease too. How prevalent is eczema?

Jonathan Silverberg: Yeah, atopic dermatitis or eczema is more common in children. Prevalence in the United States is about 13% of children, but recent studies have been quite provocative and shown that it may be as high as 7% of adults in the United States as well. So it's a little less common than kids, but certainly not uncommon either. For many patients in adulthood, their atopic dermatitis or eczema will first start actually as an adult, whereas for others it may be something they've been dealing with on and off throughout their entire childhood.

Erin Spain: And there are some people that are maybe more likely to experience this. Women? Who else?

Jonathan Silverberg: It's actually quite fascinating, in young childhood there's actually a predilection where boys tend to have it more than girls, but then at around the age of five and up and then really throughout the adult years, girls or women are more much more common to have atopic dermatitis or eczema than boys are. So we're not really quite sure and it's a phenomenon that has been observed in other allergic disorders, but it's a fascinating one. We also see much higher rates of eczema amongst African American children. Actually about twice the prevalence in childhood. In adulthood that pattern may not sort of hold up and it may be sort of similar rates, but certainly in childhood we see a lot of that. Actually one other group that we see very commonly are those that live in urban areas. Much higher rates of eczema compared to those living in more rural areas. We've actually seen a number of studies that show folks who live on farms have just dramatically lower rates of eczema compared to those living in an inner city sort of urban environment.

Erin Spain: So you can only think this has environmental impacts?

Jonathan Silverberg: Absolutely.

Erin Spain: But has that been studied very much?

Jonathan Silverberg: It has and that definitely plays a very important role, both probably in triggering the disease, but certainly in terms of perpetuating it or flaring it where there are climate factors, there's probably pollution factors as well, there's probably a stress component. There are even things like neighborhood characteristics that seem to impact the disease where folks that reside in areas where with are more parks or more libraries, more social support structures tend to have less eczema than those living in areas that are more underserved or where there's less of those support structures or less of that infrastructure in the neighborhood.

Erin Spain: You know, you mentioned before atopic dermatitis, which is different than other forms of eczema. Can you just give me the explainer there about what makes it different?

Jonathan Silverberg: The term eczema is used sort of by the lay public as being synonymous for the atopic dermatitis. But in the dermatologic community, we think of the term of eczema as being more of like a visual descriptor of what we see on the skin. And then there's a number of different disorders that can present with that kind of pattern. So atopic dermatitis or atopic eczema is one of those. Often it will start in childhood, as we mentioned, it can start commonly in adults as well, but it's about the pattern. It'll often present in the creases of the skin, so like the creases of the elbows, back of the knees, front of the neck, wrists, and ankles. It's also a pattern that from what we know is not really a reversible pattern. Meaning it's not just an allergy to one ingredient in a personal care product or not a food allergy. It's really almost an autoimmune process where the immune system is really just sort of wired to produce more inflammation and attack the skin.

Erin Spain: And what does this look like? I mean, you see some of the most severe cases. What does it feel like? What does it look like for the person experiencing it?

Jonathan Silverberg: Sure. I think the most important thing is actually what it feels like to the patient because that's really where the burden is. There's certainly a visual component and I'll touch upon that, but it's really the itch in particular that drives this. When patients have severe itch, that can be one of the most debilitating symptoms and studies have shown that itch across many disorders, but certainly in atopic dermatitis or eczema, is just as bad and maybe even more burdensome than severe pain. We see that component of it really being a very important symptom. When patients itch a lot, they don't sleep well when they and when they don't sleep well there's impact in terms of workplace productivity, there's impacts on mood, and mental health symptoms. Then we also see there's a component of pain that actually happens in eczema and that's a relatively newly recognized symptom and one that we've studied recently and shown that it's actually very common. This is not actually been on the radar of most clinicians for reasons not entirely clear, but when you talk to patients, more than half will report getting a skin pain as a component of their eczema as well. So there's, there's a lot of sort of heterogeneity or big mix of symptoms that can happen. And then visually what we see is these sort of red, scaly, thickened bumps that will happen on the skin. They can range from sort of isolated areas to covering literally the entire body. It's a fascinating disorder in that sometimes it's visually very challenging for us as clinicians to see how much is active and how much is not. It may even look fairly mild, but the patient is itching from head to toe and then we know, okay this is a different scenario. We really have to step up our treatments.

Erin Spain: You mentioned sleep, we talked in the beginning about mental health. This is one of the areas that you studied these health comorbidities that come with atopic dermatitis. So can you tell me what are some of the other ailments that seem to come with this condition? Because there are many.

Jonathan Silverberg: The most commonly recognized ones are sort of the allergic or atopic, comorbidities, things like asthma, hay fever, food allergies, nasal polyposis. We've known about these connections for actually decades and there's been some controversy whether or not these are actually sort of caused by the same mechanisms or just kind of related to each other. Those are ones that come up quite a bit and recently the field has shifted. We used to think of it decades ago as eczema was an allergic disease, kind of similar to food allergy or asthma, now what we've seen is it may be quite the opposite. It may not be that food allergy causes eczema, but that eczema actually causes food allergies and other allergies. Where when the skin barrier is broken down, sort of the junk, or the allergens of the outside world are no longer protected or shielded by the skin and they're able to cross the damaged skin barrier and trigger an allergy with the immune system. We actually see this idea that bad eczema early in life may actually be one of the strongest risk factors for patients to develop asthma, hay fever, food allergies, et cetera. So that's a very important class and we're still kind of sorting out like how do we prevent that? How can we get better control of the eczema in order to prevent those allergies? Then there's another subset of symptoms or comorbidities and I have, I think, what is perceived as maybe a bit of a provocative viewpoint on this. We've known about the connections with mental health disorders and eczema for quite some time and in some shape or form. But what's becoming clear is that these are not just these sort of like independent loose connections between two random disorders, but that the mental health symptoms are actually symptoms of the eczema. The same way I think of Itch as a symptom of eczema or pain as a symptom of eczema. I actually think of depression and anxiety as a symptom of eczema because for the most part, when you get really good control of their disease, those actually get better too in many patients. So that's a very provocative viewpoint.

Erin Spain: And you were able to just confirm that in this latest paper published in the British Journal of Dermatology, it confirmed that strong link between skin and mental health. Tell me about those results and that survey.

Jonathan Silverberg: So that study is part of the atopic dermatitis in America study, which was a US population based survey study meant to understand the burden of eczema in adults. We've known for years about some of the burden aspects in kids, but very few studies have actually sought to understand it in adults throughout the US population. What we found was that pretty much all patients had some symptoms of depression and anxiety and the more severe their eczema, the stronger those symptoms were. It actually got to the point where patients who had severe eczema, when you looked at like combinations of a bunch of different endpoints, 100% of them had abnormal depression and anxiety scores. And you know, it's in of itself quite interesting cause it's rare and research at you ever get a signal where it's 100%, but to see all patients in that severe category getting it I think is a very strong statement. I think it's actually reflective of what we see clinically, but there really hasn't been very much out there and many patients sort of feel isolated in a sense because it's not a recognized issue and they're not asked about these things commonly.

Erin Spain: Do you think having a paper like this now in the literature might make your view on mental health and eczema a little less provocative?

Jonathan Silverberg: I think certainly there is always need for more research. I think it really shows that, you know, these mental health symptoms are not happening in just some rare subset. These are incredibly common and what's fascinating is even in the milder patients where we, you know, some might poo poo and say, oh, it's just eczema. Well, no, it's not just eczema. It really can take its toll on patients. But certainly in the more severe forms where you see these really high rates of depression and anxiety, I think it's something that will raise awareness. I think that the average clinician in those struggles, well, so what do I do with this? You know, I'm a dermatologist,

Erin Spain: Right, right now in the dermatologist's office there probably aren't mental health counselors available.

Jonathan Silverberg: Right. What we're starting to learn in the field now is you may not actually need a mental health counselor. That's important too. And there's a subset of patients that will need referral to a mental health specialist, but that many of these symptoms will actually be improved by the dermatologist if the dermatologist is really achieving tighter control of the eczema and that's an area that we still need some more research on. I kind of look at this as part and parcel of managing the skin disease in sort of this multidisciplinary care setting.

Erin Spain: So there are new treatments. You were very involved in a clinical trial for the drug dupilumab, which is now FDA approved and it's being used in the clinical trials that worked in about 40% of the cases. Tell me about this drug and the impact that it is having on the eczema community.

Jonathan Silverberg: Dupilumab has really been a revolutionary for the field. We didn't have any systemic agents approved for eczema, certainly in the adult population, you know, ever in reality. I mean other than systemic steroids that have been around for decades, but the side effects are not great to say the least - they are actually terrible. So this is really the first new systemic agent. But what makes it revolutionary is not just the fact that it works well, but that it's got a very good safety profile overall and far better than what we've traditionally sort of used with respect to immunosuppressing agents and things like that. It's fascinating actually because even in those trials, so just to give you a little background, you have about 40% of patients who will get clear, right? 30 to 40% of patients who, who essentially their skin resolves completely. It's quite remarkable, but that doesn't mean the other 60% don't get better even amongst the other 60% the majority are still getting a clinical response. It may just not get to the point of clear, but they do well. But one of the endpoints that they actually looked at in those trials was this hospital anxiety and depression scale to look at symptoms of depression and anxiety and they actually found that in the studies, those patients that did well had improvements of their symptoms of depression and anxiety. And so it sort of gets that point we were talking about. It's not to say that dupilumab is an antidepressant, it's not, in fact we don't have any plausible way of thinking of it in that way. It's that when you treat the eczema successfully and you get the inflammation and the itch and the pain and the sleep better, the mental health symptoms really can get so much better over time.

Erin Spain: You mentioned that this is a very safe drug. There are some side effects. One of those is conjunctivitis or pink eye and you can usually handle that with your patients in clinic.

Jonathan Silverberg: Yeah. So that conjunctivitis signal is a fascinating one. It's not the kind of pink eye infection that we think about. It seems to be more of like almost like a little eczema around the eyelids or even just a little bit of what patients might experience with hay fever, a little redness in the eye. In the field was still sort of learning how we can predict which patients will or won't get it. It's certainly not the majority. In fact, it's probably less than about 10% that will get it, but it's actually fairly easily managed using things like artificial tears or occasionally we'll have to use a prescription eye drop. I do work together closely with our ophthalmology group to sort of monitor those. I've gotten quite comfortable dealing with them on my own, but we want to work together really better understand this phenomenon, so that we can kind of like find the best solutions for the field on this.

Erin Spain: That drug right now is just for adults?

Jonathan Silverberg: Correct. Actually, he dupilumab has already completed studies in kids and is actually being reviewed by the FDA in about a week. So we may have approval for adolescence soon and hopefully over the next few years there'll be a staggered approval for younger children and then even down to infancy. So there's sort of an aggressive development approach, but of course it needs further study and further approval, but there are a number of other treatments certainly in development and things that are available right now. What's remarkable is that even simple things like using a good moisturizer, like petroleum jelly, can really have a profound effect on the skin. Now, you know, you have to have a little bit of context when you're dealing with milder cases, sometimes just really good moisturizing can make a world of difference and actually be adequate by itself to manage milder cases. Those are often the folks who don't get in to see the doctor for it because it is a little milder. Then when you get to the more severe, or even in the mild category, but more severe than what just moisturizer alone can handle, then we start working with a prescription topical steroids or anti-inflammatory agents sort of similar to that. Then eventually, you know, if we need to go even more than that, that's where it gets tricky because we haven't had any approved agents and we start using a lot of things off label. So it's a very welcome addition if dupilumab will be approved and hopefully it will be soon for adolescents and then younger children.

Erin Spain: So a good moisturizer and you've also been able to sort of debunk a few things out there that people were doing in the past with their children, such as giving them bleach water baths that used to be common. You found that maybe wasn't the right choice.

Jonathan Silverberg: Bleach baths is still a highly controversial area. This was something that was developed actually initially by some folks at Northwestern an initial study found to be somewhat effective, although even in that initial study, some mixed results. But then, you know, over the years several different additional studies were done that really found conflicting results. A couple of studies found bleach baths were a little bit better than a straight water bath. One study found water bath was actually better than a bleach bath and then one study found absolutely no difference. When you, when you pull them all together, you actually see no significant benefits of bleach over doing a straight water bath. I think we still need more research. I think you know, when you're dealing with only four studies you have to wonder, well, could there be a group of patients that might still benefit? But I think the research really provides sort of two broad areas or new insights that need to be considered. One, many were trained in the clinical world that taking baths is somehow bad thing in eczema. Many clinicians have told their patients, we don't want you to take a shower bath more than once a week. You can imagine that that's something that does impact patients quite a bit in terms of interpersonal relationships and work and things like that and it turns out that that's actually not true that taking a bath can even be effective. It can help your disease provided that you take a few key steps like, you know, not saying in there forever, you know, not going scalding hot water. Moisturizing or medicating immediately afterwards to sort of seal in that water and really not using irritating personal care products or you know, rinse off products in the shower bath that will aggravate the skin. But I think the whole dogma shifted now to say, no, actually you don't need to tell patients to stop showering or bathing. You should encourage it. But encouraging also with that good skincare habits. The other part is that the bleach itself doesn't seem to do anything more than just having them take a regular soak in the bath. You know, they've been some interesting studies recently, actually just last week, one was published showing that the concentrations of bleach that we aim for in a bleach bath are not at all biocidal - they don't kill bacteria, they don't kill staph. So the original rationale of why we thought we were using bleach baths, it doesn't even turn out to be true. And the only way you can kill staph bacteria is by getting to the really high concentrations but are very toxic to the skin and we could never recommend that to our patients. The field is shifting. It doesn't mean there's no one who will benefit from that, but I think we need to understand that a lot more and step up the science in that area before we blanketly recommend this to all of our patients.

Erin Spain: You keep talking about a good moisturizer. What do patients need to look for? What can physicians recommend to their patients of all ages when they're looking for that good moisturizer to help with the eczema?

Jonathan Silverberg: There are a lot of good moisturizers out there and I think as a consumer it's often very challenging navigating that because it almost seems like there are endless options and perhaps there are. Especially once you start incorporating options of shopping online too. Where there are just thousands and thousands of products. I like to keep it simple. One of my favorite, at least from an efficacy standpoint, is good old fashioned petroleum jelly. It is the most effective option you will get. It's dirt cheap. It's pretty much as hypoallergenic as one can get and you can really get ample quantities of it, but it's not necessarily for everyone cause it's a little greasy and it's messy. But in the right patient, in the right context and the right method of application one can get phenomenal results out of that. For daytime use, for patients where it's a little more challenging, there are lots of more elegant and less greasy options that can be used as well. That's often a shared decision based on the tolerability, likability, texture, feel and cost. I think cost is such a big factor for our patients.

Erin Spain: Oh, I'm sure some moisturizers can go up into the hundreds of dollars?

Jonathan Silverberg: They can.

Erin Spain: What should people look for on the label?

Jonathan Silverberg: I often like to recommend things that are fragrance free. Things that are specifically marketed for sensitive skin or for eczema. There's actually a seal of approval on some products from the National Eczema Association. In truth, even those products, patients can get a little irritation too, but at least there's a better chance that some of those are going to be pretty clean. In truth, it's not always so easy to find that perfect option and it's worth having that discussion with your healthcare provider about this because every patient's different and some patients may also have a component of skin allergies or contact eczema on top of their atopic dermatitis or eczema and that changes the whole discussion because then there may be very specific ingredients they need to be cautious about.

Erin Spain: And even something as simple as keeping the moisturizer in the fridge can help with that application and sort of the soothing aspect.

Jonathan Silverberg: Yeah, absolutely. This is something that we don't have the greatest number of studies on, but anecdotally we use this all the time. Many patients with eczema, especially when the skin is really inflamed, have a very hard time tolerating their personal care products. Now once their skin gets better, it's often more tolerable, but during a flare, sometimes even water can sting and flare up the skin. Cold is often just very soothing, as in of itself, so putting the moisturizer into the refrigerator beforehand when they then apply the medicine and it's nice and cool - can have actually kind of a very soothing effect, but it also makes those moisturizers much more tolerable.

Erin Spain: You are one of the world's leading experts on atopic dermatitis and you're actually hosting a conference here in Chicago where you're bringing people from all over the world - a first of its kind. There's so much new information coming out in this area. Tell me why you're hosting this conference.

Jonathan Silverberg: Sure. So the conferences called Revolutionizing Atopic Dermatitis, or RAD, and it will be taking place at the Chicago Marriott O'Hare on April 6th and 7th of 2019 so just about a month away. We do have an international lineup of speakers and actually international lineup of attendees who will be attending. There's been so much interest in atopic dermatitis now and so much growth with a ton of new topical oral injectable treatments. Some already approved. Many in the pipeline hopefully to be approved and giving us new options for our patients. We've also had a ton of new evidence about some of the more fundamental aspects. Like best practices and diagnosis and how to properly assess the severity of patients or how to deal with those multidisciplinary aspects, like the mental health concerns, like depression, anxiety, the sleep concerns, et cetera. These are all issues that have not really been fully addressed in the world of medical education. We felt it would be best to have a conference devoted to this to really deal with high level evidence based, education. Addressing that multidisciplinary approach, that holistic approach to treating the patient and getting the whole patient better, not just focusing in on just that limited skin aspect.

Erin Spain: Tell me a little bit about yourself. How did you end up in this field, both treating patients and studying the condition?

Jonathan Silverberg: Personally, as a kid, I had eczema and it was actually quite bad, but it went away during my adolescence. Ironically when I came out here to Northwestern to treat and to study eczema, Chicago winters get me. My eczema flares almost predictably now in the winters because of the dryness and the cold. But on top of that, I'm actually, a lot of it came from research. I had done my PhD in immunology, working very closely with the allergy group at my medical school and we were doing a lot of work and interest in a translational work in eczema, asthma, and other disorders. I became so fascinated by it because it's so common yet it is so mysterious and it can present so heterogeneously. There are so many different patients that have it and yet almost no two patients exactly look alike and I kind of think of it that way. They really need to tailor treatment because of all these differences. It just got me so fascinated that I just kinda rolled with it and I kind of approached my interest from the research side before I even explored it from the clinical side. When you talk to patients and when you see how debilitating it can be for them and the amazing impact one can have on their lives, when you get them feeling better, it's truly unbelievable. It's an incredibly exciting time for eczema right now and for decades now, patients have really not had so much hope. There really is a great reason to have hope with so many new treatments coming. In dermatology now we refer to this as the decade of eczema, where the last decade was sort of the decade of psoriasis and we've had a lot of improvements there, but now there's just been this renaissance of research and clinical investigation and treatment for eczema patients and I think for those patients out there listening it's an exciting time and a time when you can really have hope that some really cool new options will be coming soon.

Erin Spain: Dr. Jonathan Silverberg, thank you so much for joining me today.

Jonathan Silverberg: Sure, my pleasure.

Erin Spain: A note for physicians to listen to this show, you can now claim continuing medical education credit just by listening. Go to our website, feinberg.northwestern.edu and search CME for more details. If you're a regular listener and enjoy the podcast, go to iTunes and rate us.