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Skin Barrier Deficiency

The skin serves a number of purposes, including acting as a physical, antimicrobial, and permeable barrier, but in atopic skin, these functions can break down and contribute to the inflammatory itch of eczema. Peter Lio, MD, FAAD, details what we know about barrier dysfunction in atopic dermatitis, from filaggrin mutations to transepidermal water loss, and explains how to begin repairing the barrier as part of the therapeutic care plan for eczema. Dr Lio is clinical assistant professor of dermatology and pediatrics at Feinberg School of Medicine at Northwestern University in Chicago, IL. He is a member of the Clinical Advisory Committee of the National Eczema Association.


Dr Lio: The skin is playing a number of important roles, and we often talk about it being the interfaced with the outside world. One of its primary jobs is keeping water and other nutrients inside our body and protecting us from allergens, irritants, and pathogens—bacteria, viruses, fungi that could potentially cause trouble. When it's working great, it's doing its job and everybody's happy.

But we know that in atopic dermatitis, no matter where you begin, there is barrier damage, or what we call barrier dysfunction. One way to put it is leaky skin. The skin is, instead of being nice and tight, it's open, so water is getting out. These allergens and irritants and potentially abnormal pathogens can get in the skin.

One thing that's fascinating is that this whole story broke with this idea that filaggrin, which is an important structural protein that we've known about for a little while, but the connection came up probably about a decade ago where people said, if you have a mutation in the gene that encodes for filaggrin protein, then the gene is called FLG, but the protein is filaggrin, so if you don't make enough of it or don't make correct filaggrin, it turns out you have a much higher risk of developing atopic dermatitis. It's interesting that thinking there is that, because when you don't have enough filaggrin, you have this leaky skin and that is the first step.

The truth is, though, that doesn't explain everybody. Apparently, in Irish populations, it could be as high as 50% of the eczema, you might be able to say…if someone says you, "Why me? Why is this happening to me or my child?" It's like, "Well, because this gene, probably, this seems to be a good marker," but as soon as you leave that, the numbers trickle down.

It's probably not just one thing. In different populations, there may be different foci, different genetics that actually are playing a role, because we know that the skin barrier is not just the physical barrier. There's different types of barriers. The physical one is the part we're talking about with the tight junction, the skin cells, and, of course, the fats—those ceramides and other lipids are playing an important role. Sometimes, people call this the bricks‑and‑mortar concept, because it does look like bricks and then the stuff between the bricks holding them together, the keratinocytes, skin cells, are the bricks, and then all the different stuff between them holds them together, but it's not that simple. There's also the microbiome layer, there's the chemical layer—it turns out that our skin makes all these important chemicals including the acidity; skin likes to stay somewhat acidic, closer to around 4.5 pH—and then even the immune layer, so all of these are parts of the skin barrier. If any one of them is abnormal, then potentially, we can have trouble.

The T-E-W-L or TEWL or transepidermal water loss, is a measurement for how much water is escaping from your skin. Now, under normal circumstances with healthy skin, it should be a very, very low number. It should be minimal. Basically, you're able to keep the water inside where it belongs and thus maintain skin hydration. When that barrier is leaky, then that number goes way up. The truth is there is a lot of variability from body spot to body spot, different times of day. There is some dynamic aspects to it. If you look at a population over time and average it, you can say, wow, this group of people, for example, those with atopic dermatitis, have a much higher TEWL in general than patients who don't have atopic dermatitis.

It turns out there are other skin conditions that also probably have barrier problems too, and of course, anytime the skin is inflamed or dry or under duress, you know your skin barrier is damaged and that of course makes you susceptible, because we know once it's open like that not only does that water come out, making it really hard to stay moisturized, but bad stuff can get in.

One of the things we'll hear for patients with eczema is that no matter how much moisturizer they put on their skin, it doesn't seem to be enough. We think that is an index that it's because it can't hold the water. It's like trying to fill up a strainer. It just keeps pouring through, is not able to hold it. It's not only limited to those with atopic dermatitis. We think that probably in the gut, there is also this same concept, or at least this similar concept, some people call it leaky gut, where there is a permeability in the gut. This seems to be associated with a number of GI diseases.

It's compelling, because this may explain how certain systems are connecting. We often talk about the skin. If you follow the skin around your lips, it becomes the gut lining. They're both linings against the outside world, even though this is the inside world, inside of us, it's still not your body. It's a tube. Really interesting to think about this. In asthma, probably there are some issues that are similar in the respiratory epithelium as well. We do see some similarities to these barrier problems across different conditions and it seems to put us at risk for trouble.

By and large, the vast majority of patients with atopic dermatitis or impaired skin barrier, they really do seem to do better if we could get them to use moisturizer and do it frequently, especially if it's a good one. There are gazillion moisturizers out there, and that is one of the problems. Sometimes people will use something and say, "Moisturizers don't help me." Then I see what they're using and I'm like, "This is a fragrancy lotion thing. This is more of a cosmetic." If we pick some of the moisturizers that are designed to help restore the skin barrier and strengthen it, I think most patients see a net positive effect. There are some beautiful studies that show this. The more moisturizer the patients use, the less severe their atopic dermatitis is.

We think not only are we replenishing that barrier and strengthening it, but we're even just putting a temporary barrier in place for as long as the moisturizer is on top of the skin, particularly when we're using heavier ointments and greasy things. You're just taking the place of that barrier. Just imagine if your window were broken, it'd be best to fix the window, but in the meantime, you might put up a board to keep people out.

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