"Me no like carrots"/Protein fragment could be target for treatment of eczema itch

Saturday--double swimming lessons again. We're getting dried off afterward, me and the two kids, and in the men's changing room they're getting some lessons in anatomy as a number of hirsute and moderately obese men shower. One of them lathers himself head to toe with soap. I kid you not, I have never seen someone so completely covered with suds, as if he'd been dipped like a sheep. What must it be like to be able to use soap like that without consequences? For me and Voov soap is something to be used sparingly if at all.

Voov, as you may know, has been on a restricted diet. For about a year or so she has eaten about eight things (others are allowed but not always available as organic produce--e.g. asparagus). So three weeks ago we were given the green light to start trying a small roster of new foods. The first candidate was carrots, which we chose for their nutritional punch. We were excited as we placed the first plate of chopped, boiled carrots in front of Voov. She picked up a piece and stuck it in her mouth.

"Me no like them. Me not eat them," she said.

And so it proved, after we offered them every day for two weeks: she doesn't like carrots. Fortunately she liked the next two items, apple and pork; we are on week two of pork and next week on to something else.

Hidden B went away last week to a veterinary conference and chose the opportunity to wean Voov off breastfeeding. That's two and a quarter years Voov has been breastfed (Hidden B is ecstatic to be able to eat dairy again) and I hope that her eczema and potential asthma are less severe because of it. I myself was fed on formula pretty much from birth. My mother says that that was what mothers were told to do in those days. I suspect but cannot prove that my food-related eczema has been nastier because of the formula--Hidden B tells me the opinion of doctors at her vet practice (now there's authority for you) is that it's better for kids to be exposed to tiny amounts of allergens through their mothers' milk, rather than be completely deprived of exposure and then hit all at once when they eat real food.

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I thought I would write a bit about a recent paper in the Journal of Neuroscience. Scientists at Yale and Johns Hopkins have found, in experiments with human volunteers, that BAM8-22, a common protein fragment found in the body can produce itch by a neural pathway independent of histamine.

Histamine is a small molecule that some foods (pickles, aged cheese, red wine) contain a lot of; it is also stored in white blood cells called mast cells that release it in response to food allergies. There are neurons with receptors for histamine, and these neurons send itch impulses to the central nervous system. This is why I scratch like a demented monkey after I eat Parmigiano-Reggiano.

But it is also known that there are other neural pathways for itch; researchers don't know many details yet. For this new paper, the scientists showed that when they poked volunteers' forearms with little plant spines coated with BAM8-22, the forearms got itchy, even if they had been rubbed with antihistamine cream beforehand.

The plant spines are called "cowhage spicules." Cowhage is famous for making people itchy, and it has tiny spines covered with an enzyme that triggers itch. A group of scientists has decided that cowhage spicules are the perfect instruments for applying chemicals that induce itch. Is that weird or what? Apparently if you autoclave (treat at high temperature & pressure) the spicules for an hour, the original enzyme is destroyed and the spicules don't make you itchy.

So the upshot of this new research is that BAM8-22 and the receptor it interacts with (its identity is known too) could be a major pathway by which chronic itch signals, like those that operate in eczema, are sent to the central nervous system. It's possible that pharmacologists may now search for drugs that inactivate the BAM8-22 receptor, and conduct clinical trials to find out whether the drugs relieve chronic itch. My guess is that such drugs could emerge in a decade or so, if a pharma company--or startup--decides that the pathway could be profitable.

Baring it at the pool--or on Facebook

So Hidden B did something evil. Not only did she go away for a five-day-four-night trip to a conference in Denver (thus leaving me to deal with the kids) but she signed them up for swimming lessons AT THE SAME TIME on Saturday mornings, which means (because she works Sats) I have to take them both. Oh boy what chaos. No parking at the pool so we have to park in the neighborhood and schlep over; then the changing room is full and there's no place to put anything down; Shmoop ends up in the wrong class, and Voov is in tears because her new flipflops are pinching her toes.

Of course neither of them is actually going to learn to swim. (Voov is only two, so I have to get in the pool with her and try to convince her to blow bubbles. That would count as an achievement.)

And afterward--moisturizing Voov or myself? In that situation, with Shmoop tearing around investigating the urinals and lying on the floor and pulling all the lockers open? Forget it.

One benefit of the chaos is that I could care less whether people notice that I have eczema. I just want to get out of there with both kids alive and all the crap we came in with, and they don't know me anyway.

I've never been keen on the water. Maybe it's because I was born on the prairies. It took me forever to learn to swim. These days I would like to swim because it's great exercise but, ironically, I found out that swimming is bad for my back. Should have done it while I had the chance!

And then there's the eczema. Ever since high school I've avoided letting other people see me anything but fully clothed. Most of my friends and coworkers probably don't know I have eczema, although they must have noticed that I'm twitchy and scratchy. I would prefer that they not find out, because there's no benefit to me. Their reaction would range somewhere from "so what" to "that's disgusting."

That too is a shame, because I would like to connect with people like myself--on Facebook for example. I know the NEA has a Facebook page and I check it out every once in a while. I see that people have problems like my own and children like my own. (Some of them ALSO TYPE IN ALL CAPS FOR SOME REASON and some of them are selling quack remedies, but fortunately not all.) But, because most of my Facebook friends don't know I have eczema--I have about 175 "friends" and apart from my wife and brother and sister none of them are clued in--I am not about to participate on the NEA page, because I don't want my Facebook friends to see comments that I write on the NEA page. That would be too much information for them. Just as it would be for me if someone was writing comments about their inflammatory bowel disease.

So I wonder whether there's a social-media way for the NEA to connect with patients and to enable them to support each other. I can't be the only one who feels uncomfortable writing openly about my eczema under my real name in a world where everybody can see everything all the time. It's like being naked in a public place like a swimming pool.

An immune link between the gut and the skin in eczema

New research led by Raif Geha at Children's Hospital Boston has revealed how the immune system connects the gut to the skin, and thus how food allergies may affect the skin.

The connection is made by helper T cells. Geha and his team were investigating, in mice, how it is that an allergic reaction that the body has to a food--and we all know that the usual way that food enters the body is when we eat it--can manifest as an eczema-type reaction when the food is rubbed on the skin. Not eaten; rubbed on the skin.

The authors of the paper claim that this is a common occurrence but I beg to differ. I've never heard of it. But they put a lot of work (and taxpayers' money) into their experiments, and their results are intriguing.

Helper T cells are white blood cells whose job it is to detect foreign material in the body, and when it's detected, to stimulate B cells to produce antibodies. What I didn't know was that there are distinct populations of T cells, determined by molecules embedded in their outer membranes, which home in on different regions of the body. Some go to the gut; some to the skin; presumably, some to the lungs, etc. What happens is that the molecules in their membranes will bind specifically to "adhesion molecules" that are found in these different regions. A T cell that homes to the gut will stick to the adhesion molecules in the gut but not the skin.

And Geha and colleagues find that T cells that originally home to the gut can be reprogrammed to head to the skin instead. They immunized mice with the egg protein ovalbumin, and then later observed what happened when ovalbumin was applied to the skin of the mice. Normal mice developed eczema-like inflammation at that spot. Mice that had been genetically engineered with T cells that did not have the skin-homing surface molecule CCR4 did not show signs of eczema. In a truly gruelling series of experiments carried out late at night by grad student slaves, the authors showed that the initial immunization generated a bunch of gut T cells specifically programmed to hunt down ovalbumin; the body then modified these T cells to head to the skin. The reprogramming takes place in the lymph nodes.

I find this fascinating; I didn't know there was such a pathway. It could be that (in the way distant future) someone will develop a way to treat eczema patients with well-defined food allergies, and in these patients prevent the food-antigen-specific T cells from homing to the skin.

The research raises one huge question for me, though. Most eczema related to food allergy does not occur because we rub food on our skin. (At least, I know that I'm allergic to parmesan, but I sure as hell don't go rubbing it on the backs of my knees.) So what is going on to connect the gut to the skin and cause inflammation in the majority of eczema patients?

Scientists: We want you to stop the itch

On Twitter I heard about this survey that the University of Nottingham is doing. You can do it too!...it's not exactly a big investment of effort. They ask you what you would like to learn from eczema research. I'd assume that they are hoping to get some interesting questions, like "how do food allergies develop in children aged 1-3" or "what are the genetic defects in structural proteins in the skin that are most strongly linked to adult eczema."

As a relatively well-educated guy with an interest in eczema, I was interested to step outside my skin, so to speak, and watch as I entered in my questions in the survey--I didn't think too hard, so they were my knee-jerk reactions, what I want to know at a primal level:

1. how can I stop scratching?
2. how can I stop scratching at night?
3. how can I stop my scratched skin from getting infected?

Not exactly PhD material, eh?

But I think this illustrates what patients want from researchers. We are not interested in the science. We want results. And there's basically one thing we want: we want the itch to stop. If the itch stops, the scratching stops, and then there's much less risk of infection. So our challenge to researchers is "figure out what's causing the itch in eczema. Then figure out how to stop it."

I do have to say that eczema is a fascinating condition, though, when you start to read the scientific literature. I just wish my interest in it was purely intellectual.

Julie Block at the NEA asked me to write a brief research summary for the next e-newsletter, about a new discovery in itch pathways. When the newsletter comes out I'll comment on it.

Here comes the asthma

So it happened, a few weeks ago: Voov showed the first signs of developing asthma. We were always aware that she might, because eczema runs in the family and my sister has eczema and asthma, and asthma is the final part of the famous Atopic Triad. Still, it is a bummer to see your two-year-old with a rubber mask over her face taking her twice-daily dose of an inhaler.

Voov had had a cold, and was in for a checkup, and the doctor noted that she had a slight wheeze; her blood oxygenation was at 95%. So, with her history, the doctor tentatively diagnosed asthma and sent her home with the inhaler and a special mask. Voov was initially pretty excited about the attention, but after a few days, applying the inhaler took two adults, one to straitjacket the kid and the other to handle the inhaler.

Then she got better or at least well enough that she didn't have a wheeze. For now, the inhaler's packed away. Voov is healthy and upbeat and I think she'll cruise right through childhood just fine even if she has to carry an inhaler with her.

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I thought I'd mention this great review I read recently titled "Epidermal Barrier Dysfunction in Atopic Dermatitis." It's from 2009 and provides an encyclopedic view of how known genetic factors are related to the breakdown of the skin barrier, and how many factors such as pH and enzymes and antimicrobial peptides are involved. It also has an interesting section toward the end featuring this graphic

with an accompanying explanation of how it is that many more kids than adults have eczema, and how the condition improves with age for the lucky majority. Basically, when we're newborn, our skin barrier is terrible, the worst it'll ever be. In the first few years of childhood, the quality of our skin improves. In those people who have minor genetic defects that affect the skin barrier, eczema develops early on but fades away as the skin improves past some threshold. People with serious genetic defects like major filaggrin mutations never see their skin improve past the threshold, so they never escape eczema.

At least that's how the authors put it. It's a pretty hand-waving theory. For one thing, many scientists think that a poor skin barrier lets in pathogens and allergens that trigger a heavy immune response early on, and that this response imprints a permanent memory in the body (in the form of antibodies) that powers reactions to certain foods. So if this "memory" is made early on in the 20% of kids who have eczema, why does it go away for most of them after the skin barrier improves?

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One final item: Anacor Pharmaceuticals has begun phase 2 clinical trials of two novel anti-inflammatory ointments for treatment of eczema. The two compounds are boron-based (this is unusual) and have shown promise for treating psoriasis in more advanced clinical trials. For a thorough comparison of psoriasis and eczema, see the most recent JACI Journal Club, which discusses a two-part review paper on the topic.