An Overview of Type 2 Inflammation and Atopic Dermatitis – MD Magazine

Transcript:

Peter A. Lio, MD: Hello, and welcome to this HCPLive Peer Exchange titled Management of Type 2 Inflammation in Atopic Dermatitis. Im Peter Lio from Medical Dermatology Associates of Chicago [Illinois]. Joining me in this discussion are my colleagues Dr Neal Jain, a pediatric allergist in Gilbert, Arizona; Dr Mark Serota, a dermatologist and an allergist at MD Integrations in Denver, Colorado; and Dr Matt Feldman, an allergist from Dallas, Texas.

Our discussion will focus on treatment selection and utilization of recently approved treatments, including interleukin pathway inhibitors for the treatment of type 2 inflammation in atopic dermatitis.

Were also going to share our thoughts on the newer mechanisms of action being studied and some of the unmet needs for patients with moderate to severe atopic dermatitis as well. Welcome, everyone. Lets get started.

Lets begin by thinking about atopic dermatitisspecifically the kind of inflammation were seeing herethis type 2 inflammation. When we think about this, we understand that broadly speaking, the immune system has 2 major arms: type 1 inflammation and type 2 inflammation. We know type 2 is the type were talking about with allergic diseases, IgE-mediated things like food allergy, asthma, allergic rhinitis, and of course atopic dermatitis. Other diseaseslike psoriasis, probably rheumatoid arthritis to some degreeseem to be on the other side of the immune system. Although we understand that its probably a little more complicated than this.

Its not quite a teeter-totter. Theres some overlap. We know, for example, in atopic dermatitis, as we get to later stages, we see the role of Th22 and maybe even Th1. We also know, fascinatingly, that its probably not the same for everybody. This is not 1 disease. There are multiple phenotypes, genotypes, and biomarkers that are part of this, and were just in the infancy of understanding this. For different groups of patients and even different ages, pediatric disease vs adult disease, there probably are very distinctive phenotypes that were just learning about.

That being said, we understand that this is generally a Th2-mediated disease, and weve been able to identify some of the cytokines that are associated with the early phases in particular and some of the moderate phases of atopic dermatitis, like IL-4, IL-5, IL-13, and IL-31, the master itch cytokine, with thymic stromal lymphopoietin being released from keratinocytes, in particular. All these guys driving inflammation, driving itch, and also damaging the skin barrier.

This brings us to that pathophysiology of thinking about it, but what does it mean for us in terms of managing the disease when we think about this from a population standpoint? Do you feel that there are populations that seem to have certain features or subtypes? Dr Jain, maybe you could talk to us a little about that to start us off.

Neal Jain, MD: You gave a great overview, and you hit the nail on the head: its different in different individuals. There are certainly distinct phenotypes that we see and different patterns of inflammation.

Sometimes the different patterns of inflammation can affect the way that skin might appear in atopic dermatitis; for example, patients with skin of color with different racial and ethnic backgrounds. Those are things we have to keep in mind.

Fundamentally, as you said, this is type 2 inflammatory disease. Although there are other types of inflammation that often can come into playchronicity, racial or ethnic phenotypethat background type 2 inflammatory pathway is activated even in those who have different phenotypes, whether you have whats historically been known as an extrinsic vs intrinsic phenotype. Type 2 inflammation is fundamentally important in the disease process.

Peter A. Lio, MD: I love it. Dr Serota, when youre seeing a patient, are there certain characteristics that make you think, This ones going to be more difficult? Or that its going to have a higher likelihood to persist or recur?

Marc Serota, MD: That breaks down to 2 things. The first part is making sure you have the diagnosis right. When I hear that a patient has failed typical therapies, either topicals or systemics, the first thing you always have to do is look at yourself in the mirror and ask, Do I have the diagnosis right? Is this atopic dermatitis, or is it 1 of the mimics of atopic dermatitis?

Assuming you do have the diagnosis right, certain factors will prompt you to the idea that the patient may be more difficult to treat. One would be if they failed prior therapies. The second would be if they have a large body surface area or more severe disease. The third would be if they have other atopic comorbiditiesconcomitant asthma or allergiesor triggers that theyre living with that they cant avoid. Those are some of the things that might prompt you to say this might be a more difficult patient.

The first step is identifying that you have the diagnosis right. The second is to identify some of the historical points and examination points that might make you say it would be a more challenging patient: increased body surface area, more severe disease, other atopic comorbidities, and other external factors that might make it more challenging for you to get that patients atopic dermatitis under control.

Peter A. Lio, MD: Thank you. Dr Feldman, when you see patients presenting with multiple allergic comorbidities, do you feel like they usually fuel one another, that theyre more challenging patients if they have atopic dermatitis plus food allergy plus asthma or allergic rhinitis? Or do you feel like you can see even isolated allergic diseases that can be just as bad or even worse?

Matt Feldman, MD: Thats a great question. Its patient dependent, and part of it is also if were focusing on the pediatric patient whos following along the atopic march. On the 1 hand, its helpful to educate the family about that atopic march and how all these other comorbidities at times can feed one another. The asthma flares as theyre playing outside at summer camp, walking through the grassy fields, etc. Theyre sneezing, wheezing, and itching all at once.

That can be a helpful way to educate the family about the underlying pathophysiology of type 2 inflammation that theyre seeing living and breathing biomarkers in front of them. At times it can, no pun intended, get us in the weeds a little. Sometimes I have familieskids and adultsthat will come in thinking that the food is the driver of their atopic dermatitis as opposed to maybe the dog in the home that they have a specific IgE of 95 IU/mL too. Sorting through those different atopic comorbidities in the individual patient is important on an individual basis because all our patients are so different and heterogeneous.

Neal Jain, MD: You made some good points, Peter, as did Mark and Dr Feldman. One thing we need to inform our patients about when we see young kids and even adults is the chronic nature of this disease. Were learning more about these different phenotypes. I agree entirely with Dr Serota. When its confusing and you see these patients with severe disease, especially with skin of color, which may have a more psoriasiform-appearing dermatitis, [we have to] look for those atopic comorbidities can help us identify that this is atopic dermatitis. [That will] help ground us in the fact that that is whats going on.

There have been some interesting studies published even recently about phenotypes of atopic dermatitis. To the point Dr Feldman was making, we know that comorbid food allergy may seem to define a population of patients with atopic dermatitis that tends to be a little more severe. We see increased levels of transepidermal water loss and decreased filaggrin expression. Its not that the food allergy is caused by the atopic dermatitis, but it helps us define a subtype of atopic dermatitis that may be more severe.

Marc Serota, MD: For patients with atopic dermatitis, its very important to assess their comorbidities for a few reasons. One [is that its] sometimes difficult to diagnose someone with atopic dermatitis as opposed to a mimic, and you can use the fact that around 50% of your patients with atopic dermatitis will have another atopic condition, like asthma, like allergic rhinitis, like food allergies. If you identify that they have 1 of those comorbidities, the first thing it can do is help you make the diagnosis of atopic dermatitis. It adds to your clinical history and can help bolster the argument that you do have a patient with atopic dermatitis.

The second reason that its important to assess for those is just like psoriatic arthritis and our patients with psoriasis, psoriatic arthritis is the game-over scenario of psoriasis. Its nice that we clear their skin, but if their joints are being affected and we dont address that, then potentially they can have morbidity associated with that undiagnosed problem. The same is true in the atopic world. We want to assess patients specifically for asthma because were not going to fix that by just giving them a topical steroid cream, for example. If they have uncontrolled asthma, 1, that might tip us into using a systemic we might not otherwise have, and 2, we have treatments that can treat both conditions simultaneously.

Its very important to assess for comorbidities, even if your specialty isnt allergy asthma immunology. If youre a dermatologist, just as we assess patients for psoriatic arthritis for psoriasis, its also important that we assess patients for uncontrolled asthma. I ask a few screening questions. How often are you using your albuterol? If its every day, youre not under good control. Are you waking up at night coughing and wheezing? Have you been to the ED [emergency department] for asthma? Have you been hospitalized for asthma? Have you ever been intubated for asthma? Those are red flags that their asthma may be poorly controlled. Youll want to factor that in when youre considering what treatment youre going to choose to treat their atopic dermatitis as well.

Transcript edited for clarity.

Read the rest here:
An Overview of Type 2 Inflammation and Atopic Dermatitis - MD Magazine