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The Complexity and Burden of Itch

Patients note that itch is the most burdensome symptom of their eczema, but what lies behind the sensation? Brian S. Kim, MD, MTR, FAAD, highlights how IL-13, IL-33, mast cells, basophils, and other mediators contribute to pruritus. Dr Kim is an associate professor of dermatology as well as the co-director of the Center for the Study of Itch and Sensory Disorders in the division of dermatology, department of medicine, at Washington University School of Medicine in St Louis, MO.


Dr Kim:  Itch affects eczema patients considerably, but it also affects different patients differently. It's a very important component of the disease. It might be, in some ways, the most important. There are scenarios in which it's not, like facial eczema, maybe even hand eczema. For the most part, it's a very important central component of the disease.

It's very important to capture itch in a holistic sense. What about acute itch? What about those flares? We did a session, and we talked about objectively measuring scratching in an effective way. We have technologies now to do that. That's very important too, because there's probably more morbidity to itch in eczema than we realize.

Eczema highlights, in a very poignant way, how itches can be played down even by the patient. That doesn't mean that it's trivial. Just because my patient who's seven, says it's OK, it doesn't mean it's OK. If he's not sleeping well, he's scratching all night long, that could have effects on his schooling, attention, his mood, overall health. There's a lot more to it.

Itch is very important. It's a hugely important part of the disease. I also think that itch is important in a way that we don't understand, and not even the patient doesn't appreciate it. We have to go further in this, because the implications of what this does in patients may be much bigger than we realized.

I'm in the camp that believes this is the rash that itches. It goes back to that there are inflammatory cascades that are set off in the skin. Some cytokine‑mediated, some probably not, that mediate both chronic itch as well as acute. This is the disease component, and we're trying to disrupt that whole process. It's these inflammatory mediators that then just bombard the nerves. IL‑1 blockade is clearly a strategy.

Surprisingly, the precise role of mast cells in eczema is still unclear and fairly debated. There are probably formed pathways in itch that are modified by mast cells, but it's not well known. In other processes, it's very clear that they're very important, and it's known to a good degree why.

We recently put out a big publication on the unexpected role of basophils. The interesting thing about basophil is that, when I was in medical school, they referred to as a vestigial cell of unknown function and significance. Now what we know of basophil is that they're very important, but they're the circulating counterparts in some way of mast cells.

They're also very different, and what's different about them is that the way in which they're stimulated despite having a very similar machinery to mast cells, it is different. The way in which they get angry is different. The other thing is, although they're not in a stick skin, they can get recruited very rapidly into the skin. They do get recruited into skin in eczema, and in work we've done in the past, we have shown that basophils are big sources of IL-4, promoting inflammation. Surprisingly, they then promote itch in a very different way, not through those cytokines, but through other molecules like leukotrienes. They do that by way of binding allergen through IGE.

I have some ambivalence about patients overly emphasizing their itch because I don't want them to be taken hostage by their disease. I don't want them to be thinking about the itch all the time. At the same time, they need to know, are there certain triggers that set off their itch? When that happens, can you take note of it? How bad it is? How severe it is? Is it affecting your sleep? Just understanding what triggers it, and what also helps it go away, is very important. If you at least track those terrible periods and what's associated with that, that can be helpful because often what happens is that patients show up and they say, "Well, I was really bad three months ago." Then we're guessing. I think it's a balance.

As I mentioned earlier, to me, it is about education and the patient's understanding their disease. The more you can empower the patient, the better it is, and the more tools that they have at their disposal.

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