Transcript
Dr. Naiem Issa: So now that we've painted the picture of atopic dermatitis and the different classes of ages and what we need to consider, when we think about acute and chronic care, if you're going to distill what is acute, what is the chronicpart of AD, especially from a therapeutic paradigm, what should we learn about?
Dr. Maureen Offiah: Acute atopic dermatitis will typically present with scaly erythematous patches, depending on the patient's skin type. In skin of color patients, we need to always remember that we may not be able to visualize that erythemathat spells acuity. So most of the time we have to go with patient symptoms, what they're reporting, severe itching, pruritus, a burning sensation, discomfort. Sometimes you have even in the acute phases already new onset skin dyspigmentation, post-inflammatory pigment changes, but that is more so more prominent in the chronic phase. So acute comes in, it's like red hot. They're burning, they're very uncomfortable. And we're doing everything to make these patients feel better as quickly as we can. Whatever topical regimen that we institute in this patient has to work quickly. Wecan't wait for topicals to start to work as far as reducing itch and burning within weeks. No, we need something that starts to work from the first application becausethese patients are not sleeping. And the idea of using systemic steroids in the acutephase, we know that that can cause a lot of rebound flares in patients with atopic dermatitis, so it's definitely not recommended. We try to avoid that whenever we can.
Chronic atopic dermatitis presents more with skin changes such as lichenification, and that's where the post-inflammatory pigment changes come in. So you have hyperpigmentation, hypopigmentation, even some erythema left behind in lighterskin patients, where you have this lichen simplex chronicus, like unified eczematouschanges, skin thickening. And unfortunately, sometimes if the patient has been usingsteroids for a while, you can even start to see that shiny atrophy that's occurredin chronic phases. So that's the main distinguishing factor as far as how they present clinically.
And now, as far as what to do in a patient that comes in with an acute flare, a few things have to be considered. The patient's age. For the smallest children, theones that are less than two years old, unfortunately with the paucity of available safe nonsteroidal topicals approved for that age, now we have to do things like ... We got to think outside the box. That's where wet wraps come in, multiple different other things come in. You have to always talk about a patient's skincare, make sure that they're not exposing to daily allergens in their regular skincare products to try to minimize flares and allergies that trigger the immune system. And depending on if the patient is already on a systemic or not, if a patient is ona systemic treatment, you can do a short course of a systemic steroid to rescuethe patient from an acute flare. But in the absence of that, using systemic steroidswill likely lead to rebound flares. So try to avoid that whenever possible.
Dr. Naiem Issa: Excellent pearls, I should say. So what I'm gathering is that weneed a therapeutic paradigm. Regardless if it's a topical only or a patient that hassystemic already on board, is that we need something to put out the fire at the beginning for the acute phase. We also need something for the longer game. Andwhy? It's because that atopic dermatitis, just like any other chronic inflammatory disease, is chronic. We don't have a cure. So we know that they're going to relapse and they're going to remit. And so how do we choose that medication? So this is, I think very interesting because we're thinking about the biology. Now, not to make this into a pathophysiology sleepy lecture, but I think it's really important because as we tee this up to the MOA, what's coming now, I think this is very important.
For the atopic dermatitis, we have a bunch of cytokines, we have pro-inflammatory cytokines, IL-4, IL-13, IL-31 and some alarmins and all this jazz, and then they signal through their receptors. And then below the receptors you have Janus kinases. That's the classic thought process of the pathophys. And we have topicals that affect different aspects. We have JAK inhibition, we have topical steroids. We also havecalcineurin inhibitors, which is more generic. But now we have more information on proteins that are regulators of the overall holistic picture. And one of them is phosphodiesterase-four, PDE4. And I actually think this is kind of magical because PDE4 is found in all the different cell types, from keratinocytes to immune cells and what have you. And the beauty is that it's a protein that regulates all sorts of cytokines, from TNF to interleukin-17 and what have you. For psoriasis, for eczema, we're talking about IL-4, 13 and so on. And there's some barrier restoration to go with it. So this is a magical protein. And so, I would love your opinion. You mentioned forinfants, so less than two years of age, we have a paucity, which is true. But we havea new upcoming topical nonsteroidal, which is going to be roflumilast. And we were very familiar with roflumilast for age six and up. So for those patients we had the 0.15%, and then for age two to six, we have the 0.05% once per day cream. But now we're about to see the new three months and older approval as well. And I think that's going to change the way that we are going to approach these patients. Do you agree?
Dr. Maureen Offiah: I completely agree. That is going to be game changing. One ofthe things that me quoting myself is, I said, "The only thing more exciting than having a new medication approved is having that medication approved for our youngest patients." Because once again going back to the previous question, when you're managing young patients versus adult, more matured skin, all of this consideration, this is more tender skin. These are little babies. These are the ones that even you as a physician, as a healthcare provider, you're looking at that child and like, "I want to do the least harmful thing here." You feel a certain way when you walk in thatroom, you'll see that mom holding that seven-month-old baby and six-month-old. They're like, "You know what? I'm sorry, but the only other option I have for you right now is a systemic option because that's truly what you have." So it really wouldbe game-changing to have these patients, our youngest patients, have a fighting chance. A fighting chance to have the disease, the atopic dermatitis treated with really safe options, the ones that help their parents sleep at night, the ones that will have less of the parent that I had this evening say, "I just don't want a steroid. I don't want a steroid." Something that will make them feel comfortable as these children are growing. AD impacts not just the child, but the entire family. So having this PDE4 inhibitor, which as you mentioned, the beauty of the PDE4 enzyme is that it's in all of the cells and it's kind of like a broad anti-inflammatory medicationbecause of all the cytokines that it impacts. It has a direct impact on the nerve endings that cause itch. So these patients are going to sleep better. They're going to be more comfortable. So it's great, because as of right now when it comes to the topical world for the less than two years old, all we currently have is steroidand some less than ideal nonsteroidal options. They just haven't really worked. So having this for these patients, one, it creates a medication that this patient can conveniently apply once a day. The convenience of it for the parents. These parentsspend several hours a week taking care of their child with atopic dermatitis while working a full-time job and managing other children too. So having a safe option, nonsteroidal that it can apply once a day, that it can taper off and restart whenever they want, and we can play around, make a schedule, this will be truly game-changing for these patients, as we know that intrinsic AD still is most prevalent in infancy.
Dr. Naiem Issa: Fantastic. And yes, totally agree. The PDE4 that is found also in nerves, which I failed to mention, so thank you for that, we also have 48-hour itch reduction data across the different age groups. And I think also what's really important aboutroflumilast cream is twofold. So one, the technology of the vehicle is so important that it's made without any penetrators, no penetration enhancers, no parabens, no known allergens and so on. So this was made for the AD patient. So I love that about it, and I love that there are different strengths or different concentrationsfor the different ages, to really show that precision for the different age groups, depending on their body surface area-to-mass ratios, as you mentioned before.
