Give to the National Eczema Association. I did.

'Tis the season for giving. I just donated $100 to the National Eczema Association. You should too.

If I keep this up for 10,000 years, I'll have reached my goal!

Fingernails again/Atopic Dermatitis Research Network update

A nail-cutting night again for Voov. She's been mangling herself again. Not too terribly, but her hands have gotten all red and rough. On nail-cutting nights, at bathtime Hidden B closes the toilet lid and sits on the top with Voov in her lap, and cuts her nails with the clippers. Shmoop's job is to choose a pile of books for me to read to distract Voov. This he is very good at-- he picks the baby books, such as "The Going to Bed Book" or "Moo Baa La La La," rather than the ones he wants me to read when he gets HIS nails cut: National Geographic illustrated titles such as "Eurasia" or "The Mammals" (he likes the exotic animal pictures).

There's one issue with Voov that is somewhat disconcerting to us. Her back is, to put it delicately...um...a little hairy. There's no doubt that she's a mammal. Occasionally we wonder whether the steroids we're putting on her--which are relatively mild, but still known to have hormone-mimicking side effects--are doing something weird. Or that maybe the stronger steroids I put on myself are lingering on my hands and somehow getting into her system.

But the furry bits (we're talking downy, not out-and-out hirsute) bear no relation to where the steroids are going on. We haven't been putting steroids on all over her, which is when systemic effects are supposed to occur. And Hidden B tells me that her sister was always "downy," so maybe it runs in the family.

* * *

I was wondering what was going on with the Atopic Dermatitis Research Network, the $31 million multicampus NIH-funded consortium to investigate why eczema patients are vulnerable to MRSA. The ADRN is the new version of the Atopic Dermatitis and Vaccinia Network, a large study now wrapping up.

So I wrote to Donald Leung, the scientist in charge of the ADRN. (He's at National Jewish Health Center in Denver.) Judy Lairsmith, the ADRN's program manager, responded:

We are still working on setting up the Registry/Genetics protocol for the Atopic Dermatitis Research Network. This is a long process as you can gather. The protocol has to incorporate input from all the participating centers, plus the data coordinating center Rho, Inc., and has to go through several layers of approval at the NIH. Current plans are to start enrolling in February or March. Once the study is approved by NIH it must be approved by the [institutional review boards] at each of the institutions where subjects will be enrolled.

During my Ph.D. I had to get an animal experimentation protocol approved by a national laboratory. I filled out a lot of forms. My brain boggles at extrapolating from my experiment to the Kafkaesque bureaucratic demands of a 10-institution trial in human subjects. Judy must be a machine.

We'll have to wait a couple months yet to see exactly what trials will be done where. Participating institutions are all over the U.S. (list at the bottom of this link) so there's a good chance there's one near you.

I'm taking a break from blogging until January 3rd. Back just in time for New Year's resolutions! I know you'll be making some. Until then, enjoy the holidays.

In which the author does something dumb

I heard recently from a reader, Jon, who related how his wife was able to clear up her hand eczema by quitting dairy and eggs. Jon sent me a photo of her palm. To anyone with normal skin, it would have appeared inflamed, but to me or anyone else living with eczema, it was obvious that her hand was in recovery. Yikes--I've never had it on my palms before, and hope I never do. I'm sure we all wish Jon's wife the best in controlling her hand eczema. It's a bummer to have to give up dairy and eggs, especially with Christmas looming, but a remission from itch is a fine present to get in exchange.

Even though I often write about eczema and food reactions, I'm not immune to doing dumb things myself. Here's one. I was barely able to type out that last post of mine (on Friday) because I was scratching the hell out of my arms. Recently, I've been missing real Parmesan cheese. Since I discovered that Parmesan gives me a terrible reaction, I've been making do with the Kraft version, which any Italian would consider an abomination. But it had been three years since I'd last had Parmigiano-Reggiano, and you know how food reactions can be maddeningly inconsistent. I thought I would try it again. I bought a hefty chunk at the cheese shop a couple weeks ago and started grating it onto pasta dishes. For a while, my body let me get away with it. But last Friday, BAM! after I'd eaten some, an otherworldly itch revved up in my forearms that scratching just made worse. (But try not scratching.) It was pretty funny, typing my eczema blog and stopping every few minutes to claw away like a demented monkey.

But somehow, I felt in control, knowing exactly what was causing the itch--the histamines in the aged Parmesan--and that it would ebb away to nothing overnight, as it did.

Won't do that again in a hurry.

* * *

Some relevant news out of the University of California, San Francisco last week, for anyone interested in that story about how children are less likely to develop eczema if their mothers, while pregnant with them, worked on a farm or lived with cats. UCSF researchers have found that the fetus has an immune system of its own independent of its mother's; and that the fetal immune system develops a tolerance to most foreign antigens to which it is exposed. (This prevents a reaction to the mother's cells.) Once the baby is born, its immune system switches over to fighting foreign antigens.

Maybe if you expose the fetus to cat dander while it's still in the mother's body, it develops a tolerance for it that persists after the child is born. I know that cat and dog dander are pervasive in our environment, so much so that virtually everyone is constantly exposed to them. Could cat dander by itself be responsible for a significant fraction of eczema?

* * *

This week, I'm proud to observe that End Eczema has passed 1,000 pageviews. Any blog of real standing gets several thousand pageviews per post, so I've got a long way to go!

Also, at least a few people are finding this blog on Google, which is good to know. For a while, it was completely invisible.

If you're wondering who your fellow readers are, here's the breakdown by pageviews:

United States    792
Canada        49
United Kingdom    40
Germany        34
Australia        31
Denmark        18
Malaysia        18
Singapore        10
Netherlands        8
South Africa        5

Thank you all for reading.  It's an hono(u)r to write for you.

The plot thickens (as the skin gets thinner)

A paper published online today in the Journal of Allergy and Clinical Immunology changes our picture of skin barrier defects in eczema. A large research group (from eight institutions, including six in the U.S. and two in Germany) has shown that there is another upper skin layer protein besides filaggrin that, when mutated, is a likely cause of eczema.

The newly fingered culprit, claudin-1, is a component of "tight junctions," which bind neighboring cells together and form a seal against permeating allergens and pathogens. Tight junctions occur in the layers of the skin BELOW the stratum corneum. It is in the stratum corneum that filaggrin performs its job of flattening skin cells and getting digested into "natural moisturizing factor."

The paper is pretty comprehensive. The scientists found that

• the skin of patients with eczema contains much less claudin-1 than skin from "normal" people 
• afflicted skin is much more porous to ions than normal skin
• knocking out claudin-1 from skin cells increases the permeability of a layer of these cells
• in patient samples, the less claudin-1 that is present, the higher the levels of IgE antibodies
• and, in a population study, there are several point mutations of the claudin-1 gene that are statistically associated with eczema.

There are also several aspects of the research that are important to patients with eczema:

I saw in the funding acknowledgements that the lead author, Anna De Benedetto, and the senior author, Lisa Beck, both from the University of Rochester (NY), were funded to some extent by the National Eczema Association. Go NEA!

In the research, the authors made extensive use of samples from the Atopic Dermatitis Research Network, which is the precursor of the Atopic Dermatitis Vaccinia Network (a $32 million behemoth of a project that is 100x larger than the average NIH-funded eczema grant).

And I note that the University of Rochester has applied for a patent for the concept of using drugs to stimulate claudin-1 expression in the skin as a method for eczema treatment. It's funny; I've spent time as an engineer in industry and I work all the time with technology transfer and startup companies, but I was raised in a family with decided socialist tendencies, one of these being a knee-jerk anti-industry outlook. Or maybe that's just me. While I've learned to see that not all capitalism is evil--for instance, what would I do without Aveeno, or the companies that manufacture my steroid ointment? And don't I like my iPhone and the MacBook I'm typing this on?--my immediate reaction upon learning that a university has taken out a patent is to think "The greedy so-and-sos."

But that is misguided. And I quickly readjust; a patent is absolutely necessary to protect the intellectual property in a case like this. In the end, if a claudin-1 stimulant is an effective treatment for eczema, it will be a company that has to develop it and take it through clinical trials, which are horrendously expensive. (The rule of thumb is that it costs $1 billion to get a new drug approved by the FDA.) No pharmaceutical company or venture capitalist will invest in a drug lead for which the intellectual property isn't secure. It is good for you and me that the University of Rochester has immediately begun the patent process.

Staph: a weakness for iron

I don't know why I did that, but I had to get it out of the way; write a post about red wine and the symmetry of itching. Now, here's what I intended to write about: a story that appeared in today's New York Times about new research on Staphylococcus aureus. Scientists at Vanderbilt University have found that S. aureus has evolved to plague humans, and that it's specialized to extract iron from our hemoglobin.

Now I expect that the problem that eczema patients have with S. aureus is more to do with cracks in the skin barrier and surface pH (S. aureus likes it alkaline, and eczematous skin obliges; normal skin is acidic). But I am intrigued by the role iron seems to play. Pathogenic microbes, it appears, need iron to live, and they don't get it by eating spinach or red meat or drinking red wine. They get it from us. They get it from our blood.

In another recent paper I covered, the authors mention that the skin is an iron-poor environment, and S. aureus actually has an iron sensor that, when there isn't any iron, helps the bacteria adhere to skin. Maybe this is to help it infiltrate the skin and get into the blood.

What the scientists find in this latest paper is that S. aureus is much better at binding hemoglobin from humans than hemoglobin from mice. The bacteria grow better when they feed on the human version, rather than the mouse version. And they have a receptor for hemoglobin, called IsdB, which is essential to hemoglobin capture. Without IsdB, S. aureus is crippled.

This is interesting, but for you and me possibly the most important result of the paper is that the authors show how useful a transgenic mouse model--an animal that has one copy of the gene for mouse hemoglobin, and one copy of the gene for human hemoglobin-- is in the study of S. aureus. If you study S. aureus using "normal" mice, the pathogen doesn't have access to iron like it does in humans, so it may be behaving differently in other ways too. Scientists using this new transgenic mouse will be more confident that their results are relevant for humans.

In particular, I wouldn't be surprised if a number of studies in the Atopic Dermatitis Vaccine Network (which is focused on MRSA) adopt this transgenic mouse as their model animal.

Sangria and the symmetry of itch

I've mostly recovered from my evening out in the rowdy company of science writers. What I'm recovering from is not the socializing but the bad sangria at the tapas bar we went to. I'm sure they make it from what's left in the wine bottles from the week before.

Red wine has much higher histamine levels than white wine. Histamines cause itch. Therefore, if I'm going to drink wine, it should be white. But I don't like white wine-- I like red wine. (Plus, the idea of white sangria is vile.) I pay for my stubbornness.

So I woke up this morning with the skin on my right ankle all torn up. Must have scratched it in my sleep. I've also been scratching the back of my right wrist this week. Have you ever noticed a weird symmetry with eczema? Usually, if you have a patch on the right side, you have one on the left side in the corresponding place. And if you have a patch on your arm, you have a patch in the corresponding part of your leg on that side. Or at least I do. If there's something on the inside of my elbow, there's something on the inside of my knee. If the forearms are acting up, then the lower legs are in the game. Not always, but enough to make me think there's some weird connection in the motor part of my brain.

Oh, another thing-- if one hand is scratching, I find the other hand is also compelled to scratch in mirror symmetry. Sometimes I have fun with this, kind of like tickling the belly of a dog and watching its leg kick. I'll use one hand to scratch, and put the other hand on a towel or tablecloth and watch it do its thing by itself.

Thinking big about eczema philanthropy

Posting a bit early tonight. I'm off to a holiday party in a bit: the Northern California Science Writers' annual shindig. These events are always great for networking. Science writers love networking, because we're all freelancers and entrepreneurs at heart, and each new person you meet might give you a great story idea, or be a potential editor, or have a job lead, etc...

The new person can also be further ahead in his or her career than you are, or have just published a book, or signed a film contract-- but since, at these socials, I usually have a drink in hand, I tend to look at the bright side of someone else's success. It sets a new standard, something to aim for. It gets me excited about possibilities. That's how jealousy works for me, at least: it lights a fire under my ass.

I haven't met anyone yet who has started a blog like mine, though!

Something I keep asking myself is how exactly I plan to get to $1 million in my fundraising efforts. Is it reasonable to expect that I will inspire people I have never met to make donations to the NEA and write "research" on their checks? And for that to add up to $1 million?

I'd be surprised if that worked.

When I started this blog I had a grander vision, and I still do. My vision is not pie-in-the sky. Here it is: I live in the San Francisco Bay Area, as do a lot of successful, wealthy people. (I am not one.) Some of these people are at the stage in their lives when they are considering philanthropy. They want to donate to a worthy cause, and we are not talking about peanuts. Marc Benioff just gave $100 million to UCSF.

What if I could convince one or more of these people that a donation to eczema research would be better than charity? A donation could be an investment. Applied with precision to the right project at the right stage, an amount of $100k or more could enable a scientist to conduct proof-of-concept research that could lead to venture capital funding for a spinoff company. Or it could be used as convincing evidence of public support on an NIH grant application. The original donation would be multiplied many times over.

The way that these donations get made is through personal connections. A donor must be convinced in person; must LIKE the one who's doing the convincing, and believe in their sincerity. Often, one wealthy individual will host a dinner to which they invite their friends, and introduce the topic: say, a disease that affects a lot of people in the Third World; then get out his or her checkbook, write a check for a million dollars, and say "That's what I'm doing. What are you doing?" It's a social, human phenomenon.

So I need to connect with donors myself. I don't have to host a dinner (nobody would want to eat at my house, with the food splatters from the kids) but I need to meet someone who can. This blog is my way of making that initial connection. I'm casting my net across the world, but really just hoping to catch fish in the Bay Area.

Eczema and the hygiene hypothesis

There's a story making the media rounds right now, based on an article in press at the Journal of Allergy and Clinical Immunology. In a nutshell: if women work on farms, or live with cats, while they are pregnant, the children they then give birth to are about 20% less likely to develop eczema. The results came out of a population study conducted by an international, mostly European group. Readable Reuters version of the story here.

One result is particularly interesting-- the finding that the children's risk of developing eczema dropped further with each additional species of animal to which the mothers were exposed. For three or more animals, the risk of eczema dropped to 50% compared to the average population. This "dose-response" is convincing evidence that the effect is real.

This supports the "hygiene hypothesis," that increasing numbers of people in the developed world are getting allergic disorders because they're not exposed enough to microbes when they're young. The hygiene hypothesis says that if you're exposed to bacteria etc. from pigs, cows, and sheep, the type 1 helper T cell arm of your immune system gets a good workout, and this suppresses the overactive type 2 helper T cell arm found in allergic disorders.

But: so what? This kind of research is neat, but you wonder what we are supposed to do with it. Not everyone has, or wants, the opportunity to muck out horse stalls so that their offspring have their chances of getting eczema reduced by 20%.

And cats--what's up with that? There's a lot of research out there showing that cat dander is a major allergen for eczema. Perhaps you should keep a cat until the moment of birth, and then give it away and vacuum the house thoroughly.

The study's authors (as one would expect of academics) make the caveat that "we did not study infectious diseases." So these kids who didn't develop eczema may have developed all kinds of other problems caused by microbes from animals.

This suggests that we need not abandon the hypothesis of good hygiene. I'm the dad of two kids under 4, and I know all too well where they put their hands. They need to be washed.

You are not alone

A fellow eczema blogger, Cindy, posts that she's having a bit of an existential crisis, at least as far as blogging goes. She's got seven kids, three with eczema, which puts her in a different league from me. It's a wonder she has time to write anything. But it doesn't seem to be the demands of childcare that pose the problem. The problem, she says, is that

...I haven't learned anything new about eczema and I don't know what I can post that would be any help to others. And is it much help if what I have learned doesn't provide any significant improvement to our kiddos? Is that even too much to reach for, that eczema may be a thing of the past? I feel I have more questions than answers and have followed many leads that haven't led anywhere. Yet if I am just sharing my frustrations with eczema in our children, what is the point?

I can relate to a lot of what Cindy says. I feel like I am learning a lot about what science currently knows about eczema; but scientists are years from nailing down all the details. And cures lag behind knowledge by the time required for clinical trials. What I am learning about cutting-edge research isn't going to cure anyone.

There are practical benefits to getting the big picture of eczema, though. Since I began this blog, I've realized that using the right moisturizer is more important than I'd thought, and also that we ought to be using bleach, or some acidic cleanser (e.g. Sebamed, pH 5.5) to control Staph aureus on Voov. I'm learning and sharing useful information.

That eczema will someday be a thing of the past is not too much to hope for. But realistically, a "cure" won't be around for another generation, although a patchwork of discoveries will improve our quality of life incrementally. (The day there's an effective drug that shuts down itch fibers, I'm busting out the Dom Perignon.)

This occurred to me: what if we find that there is a magical barrier cream that, if you apply it religiously to your infant for three years, will prevent eczema for life? As a new parent, you're going to have to learn (probably, via genetic test) that your child is at risk of developing eczema. Then, if you don't have eczema already, you won't know that it's a serious condition to avoid at all costs. You may not think it's worth applying the cream, especially if it's expensive. So you won't use it. And then your kid will develop eczema, and you'll feel guilty because you could have done something about it. Compliance will be a significant issue, once a cure is discovered.

But back to the present day. As for blogging your frustration with eczema: that IS the point. We want you to share, because we have the same frustrations. Most of are isolated in our family lives, with our only connection to anyone who cares about eczema being through our doctors. We don't connect to each other much at all. The doctors can't show true empathy-- they have to maintain a professional distance. We who live with eczema need to hear from each other so we can share stories, lend support, and know we are not alone.

Moisturizer alcohol burn bad; acid moisturizer good

Voov had another dermatology appointment today. Nothing urgent; just a checkup to see how she's doing on her restricted diet. The new development is that we are not to apply steroids unless she's having a significant flare. Hidden B has, it turns out, been putting Derma-Smoothe on Voov every second night (Hidden B and I trade kid duties on alternate nights) and every morning. "I can't tell what's a significant flare," she says. "They all look significant to me."

I, on the other hand, don't think Voov's skin has been bad for quite some time. So, on my shifts, I haven't been putting any Derma-Smoothe on. This is what happens even in a two-doctorate family: we don't know exactly what we're supposed to be doing with our kid.

I mentioned that recently I got suckered into buying some generic moisturizing "creme" at CVS. It sits right next to the Eucerin, comes in the same kind of jar, and costs half as much. Why do I have to learn this lesson over and over again? The CVS creme sucks. It's slippery and actually burns my skin, although the ingredient list is virtually identical to Eucerin's. (Not perfectly identical, though, and I'd guess that the CVS version has more alcohol.)

Anyway, Hidden B found Eucerin on sale at Target and got me two jars. So I chucked out the CVS stuff. Burn begone.

This month's Journal of Allergy and Clinical Immunology has an article you'd find interesting. (Editor's summary here.) Let me recap it for you.

Two amino acids that naturally occur on normal human skin can slow the growth and reduce the infectious potential of the bacterial pathogen Staphylococcus aureus, a group of Irish scientists have shown in laboratory experiments.  

S. aureus colonizes the skin of 5% of people without eczema, and 90% of people with eczema; it infects broken skin and secretes molecules that cause and prolong inflammation.

Normal skin controls S. aureus with antimicrobial agents and an acidic pH (about pH 5.5, compared to normal cellular pH of about 7.4). I am not sure what acids are responsible for this low pH; however, two products of the breakdown of the molecule filaggrin (see here and here), "UCA" and "PCA," are amino acid components of "natural moisturizing factor" known to hydrate the skin and possibly contribute to its acidity.

The scientists explored whether UCA and PCA could, in a test tube, inhibit the growth of S. aureus. The answer was yes. UCA and PCA also reduced bacterial production of proteins necessary for S. aureus to colonize skin and evade the immune system. The interesting thing is that the scientists found the same inhibitory effects when they used hydrochloric acid instead of UCA and PCA. So the acidity of amino acids, rather than some other chemical property, is responsible for much of the bacteria-controlling effect.

However, there is one area in which UCA and PCA appear to have special properties: they greatly reduce bacterial production of one iron-sensing protein that helps S. aureus stick to skin cells. Hydrochloric acid does not do this.

If anything from this research might prove useful in the future to eczema patients, it would be that chemists might consider adding UCA and PCA to moisturizers to provide antibacterial control. There is evidence (referenced in the paper) that acidic moisturizers help suppress S. aureus.

Allergies: Better to eat foods than to waste away

So I read through the new NIAID guidelines for doctors on how to diagnose and handle food allergies.

It's complicated. There are so many kinds of allergies.

But, in short: many parents are needlessly restricting their kids' diets because of the fear of allergies, or the fear that the kids will develop allergies. As a result, I infer, some kids are growing up with unbalanced diets that can have knock-on effects on development.

The authors of the guidelines say that blood IgE tests for specific allergens are not, by themselves, enough to identify an allergy; nor are skin prick tests. Instead--as most of us already knew--the only true test is to eat the stuff and see if anything happens. And it's best if you eat the stuff in a double-blind trial in which neither the doctor nor the patient know, at the time, whether the patient is eating the candidate food or a placebo.

Alternatively, especially for non-IgE food allergies, you can drop a suspect food from your diet for a while and see if there are any changes. The authors recommend only dropping one or two foods at a time.

The authors make a number of intriguing points.

• Food allergies and eczema are highly associated; but you can develop tolerance to a food and it won't cause problems thereafter.
• Conversely, it's possible to become desensitized to a food if you eat a lot of it, but this desensitization can wear off. The authors only briefly touch on this point and don't list a reference.
• You can have a lot of IgE that binds a food, but not have an allergy. This is why blood IgE isn't so useful, and implies that there are other factors downstream of IgE that are altered in eczema patients: possibly a mast cell imbalance.
• You can have a non-immune reaction to food that can affect your quality of life. (E.g. lactose intolerance. I myself have reactions to aged cheese and pickles and concentrated tomato paste, which contain a lot of histamine; I have reactions to hot peppers and alcohol, which dilate blood vessels in my skin and somehow cause irritation.)
• Most kids will eventually tolerate all foods but tree nuts and peanuts.
• The authors do NOT recommend using allergen-specific immunotherapy to treat food allergies arising from IgE. I'm guessing this is because of the risk of anaphylactic shock. However, a large meta-study just found that sublingual immunotherapy was effective and virtually risk-free for treatment of hay fever. It must be that the allergens from pet dander, pollen, and dust mites are somehow less dangerous.

Where is the science going on this? At the moment, antihistamines are considered the way to manage non-lethal food allergies. (Epinephrine for anaphylaxis.) The authors say

Drugs that alter the immune response to the allergen are commonly considered the most likely candidates for such therapy in the future, but these treatments are not currently recommended.

I wonder whether there are any drug candidates in the pipeline.

NIAID lays down the law for food allergies

Voov's got this red inflammation on her face, around her mouth. Suddenly broke out today. It looks like she's having a reaction to something, maybe food, except that she's been eating the same stuff she has been eating for many months. Zucchini, broccoli, sweet potato, corn, tofu, rice, chicken, turkey, pear, banana-- and that's it. She doesn't avoid certain foods, she excludes everything but.

It just occurred to me that maybe she ate something off the floor. Shmoop, at 3.75 years, doesn't have a spotless record in conveying food from plate to mouth. Maybe he dropped a noodle or piece of omelet or something that Voov hoovered up when we weren't watching.

Anyway, although her skin was good for a long while, it's flaring up just in time for her dermatology appointment on Thursday. That's the way it should be. Much better than right afterward.

You've probably seen this all over the news: a panel of experts vetted by the National Institute of Allergy and Infectious Diseases (NIAID) has just released guidelines for clinical diagnosis and treatment of food allergies. There's what appears to be a decent writeup in the Wall Street Journal health section (I saw several other instances, but this was the best).

1. The original paper is--guess where--in the Journal of Allergy and Clinical Immunology, my favorite eczema mag. The paper is a doorstopper. (At 14 pages, it appears to be a shortened version of the real guidelines!) I'm only a little way into it, but I do mean to go through it and find what parts of it are specifically applicable to eczema. I want to comment on a couple things that jumped out at me though. they're defining a food allergy as "an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food"-- that is, at first glance, they're not considering the magnitude of the reaction
2. they're distinguishing between a patient just having IgE antibodies to food allergens and having an actual allergic reaction. Having antibodies is called "sensitization" and doesn't necessarily imply an allergy.
3. this from the WSJ piece: "It's especially hard to pinpoint a true food allergy in young children with eczema, since they make IgE antibodies to many foods. 'If you did 100 food tests, all 100 would be positive. That's what we see from patients coming in from around the country,' says David Fleischer" of National Jewish Health in Denver.

That's in line with what I heard when I requested a RAST test for allergies about 5 years ago. My allergist told me that people like me, with eczema, just overwhelmed the assay because we had so much IgE floating around.

I'll be interested to see if there's anything new in these guidelines that can help me and my daughter. It's hard to imagine, because I'm a trained scientist, but after 40 years of living in this body I am still not sure exactly what it's allergic to.

Will we see "itch centers" in the U.S.?

One thing that often gets neglected in articles about eczema is itch. To those of us who suffer from eczema, the itch is virtually the core of the problem. No itch? Then we wouldn't scratch. And we wouldn't have the gashes and tears. Who would care about dry skin or a bit of redness if we could get into bed at night knowing that we wouldn't stay awake, or in a half dream-state, frantically scraping our hands or heads or the backs of our knees or whatever.

Just typing that last sentence, I had two involuntary fits--now three--where my hands leapt of their own accord--now four, five--to my scalp or face and indulged themselves in a frantic scrabble that must seem twitchy and obsessive to a "normal" person.

Chronic itch, it seems, can sensitize our central nervous systems so that very minor stimulation triggers an urge to scratch. Or we just get itchy for no reason at all. The sensors in our skin fire by themselves. But you read articles about eczema that talk about moisturizing and managing your diet as if our rashes appeared by themselves. These articles must be written by people who don't have eczema themselves.

I read today in Skin and Allergy News that the U.S. may in the near future see certain premier medical institutions found centers for itch treatment. Apparently Europe already boasts several such centers, and I interpret the article to say that the centers have a centralized database of tens of thousands of patients. The collected data is being used in studies to determine what triggers itch and how doctors might alleviate it.

One treatment for chronic itch, the story says, is "second-generation antihistamines." Intriguing. I didn't know there was such a thing. All I know is that what must be first-generation antihistamines--Claritin and Allegra--do nothing for me.

The article also mentions "neuroleptic" (read: antipsychotic) meds and drugs that affect the central nervous system. Now, I'm not anti-Western medicine by any means, but the hairs on my neck stood up a little when I read that part closely. If it's a choice between being the slightly weird guy who's always scratching something and being the impotent, lethargic insomniac, I'll go for Itchy 'n Scratchy.

Of course, there are other conditions besides eczema that cause itch: liver or kidney disease, or shingles. And when you start scratching a hole in your head, it's time to medicate.

The new centers in the U.S. may launch at the University of California, San Francisco; Washington University in St. Louis; and Harvard. Since I live in the SF Bay Area, this is pretty exciting for me (and not so exciting for you, if you don't). But there's another issue: this is the U.S., with its messed-up medical "system," and my current insurance doesn't cover treatment at UCSF, which is ridiculous, since I WORK at the University of California. Say UCSF launched an itch center, and I really needed an appointment; it might be that my doctor could refer me to UCSF. Or I might have to pay out of pocket. It would be a lot simpler if the U.S., or even California, had something approaching a single-payer healthcare system.

These centers are, at the moment, pie-in-the-sky. But they could happen. Timothy Berger, MD, at UCSF, claims in the Skin & Allergy News piece that "The NIH is moving to a model of having major itch referral centers at several sites." Berger was quoted commenting on a recent "roundtable" session hosted by the National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS), part of NIH: the roundtable was focused on exclusively on itch, and was the first such discussion held by NIAMS. It came about because of lobbying by the National Eczema Association, according to Julie Block, the NEA's CEO, who told me so last week in our conversation. "We're so excited we got NIAMS looking," she said. "There's nothing ever been done so specific to itch." Block, or another NEA representative, was invited to take part in the roundtable.

Did I mention that you should donate to the NEA?

According to Trish Reynolds, the media rep at NIAMS, they'll post a meeting summary by the end of December. I'll be interested to read it and to get comment from the scientists involved about what they think is feasible.

End Eczema's mission: please donate to the NEA for research

This past Thursday I spoke on the phone with Julie Block, president and CEO of the National Eczema Association, and Diane Dunn, the NEA's communications and program manager.

I thought that Julie and Diane's outlook was very similar to mine. Eczema is a disease that affects millions of people (in the U.S., 20% of children and 2% of adults, which probably means that 50 million people live with it in the home). It can drastically affect quality of life. It leaves a sufferer open to serious infections such as MRSA, and disqualifies them for military service.

And yet you hardly ever see eczema mentioned in the media. (Can you think of any blogs? Any celebrities?) You rarely, if ever, hear of any fundraising efforts for it. It is, despite being a disease of the skin--and we use the term "skin deep" for something that you have to look beyond to find the essence--virtually invisible.

This is probably because most of us cover it up. I know I do. Why would I want to expose an unsightly rash that reveals my lack of self-control? I wear long pants and shirts with collars and long sleeves. I go to the swimming pool only with great reluctance. People stare, sometimes. They hustle their babies away from your kids to avoid what looks like a contagious rash. We who live with it are ashamed; those who don't are ignorant.

The NEA was the first eczema patient advocacy organization I have heard of in my lifetime. I think they're amazing and they deserve our support. They are primarily dedicated to education and outreach; and this is good. We need to educate ourselves about the best therapies. We need to educate others so they understand. We need to exert pressure on our representatives in government so they direct federal research funding to eczema.

The NEA doesn't make a priority of research, and it can't be faulted. If you've got an annual budget of $500k and several salaries to pay, along with the travel expenses of a national association, you can't  make a significant investment in research. A single molecular biology laboratory, at any major university or institute--Johns Hopkins, U. of Washington, Stanford--runs on at least $1 million a year. A single graduate student costs $50,000 a year. Reagents, antibodies, experimental animals are terribly expensive. The responsibility for funding the research effort lies with the federal government, via the National Institutes of Health.

But there are ways in which grants on the order of $100,000 can make a difference. They can prime the pump; often, in academic research, to get money, you need to have money already, because many agencies will only deliver matching funds. And if you can show that someone believes in your project to the extent of handing over $100k, you can make a better case for why the NIH should give you $1 million. The NEA has seen this happen with grants to researchers Eric Simpson and Gil Yosipovitch.

Also, there is one crucial, oft-neglected zone called the "valley of death." Scientists may make a discovery, funded by the NIH, and this discovery may hold the potential to be a world-changing cure, but if it doesn't get translated into a product or service that can be delivered or manufactured by a commercial company, it stands virtually no chance of helping anyone in the real world. NIH funding drops off steeply after a discovery is made. And venture capitalists won't invest in a project or startup that hasn't shown a viable prototype or undergone clinical trials. The "valley of death" is the arid region between federal and venture funding where many promising ideas have met their end.

Proof-of-concept funding, in packages of $100k, can enable an academic scientist to fund a postdoctoral fellow for a year and buy equipment and supplies to run crucial experiments, build vital prototypes, and do the research to show that their technology has a market. Two examples of institutes that provide this type of funding are University College London Business and QB3, the California Institute for Quantitative Biosciences. In the U.S., proof-of-concept funding can enable a startup company to win a federal Small Business Innovation Research (SBIR) grant that helps it get off the ground.

So: if the NEA were able to make several annual awards of about $50-100k, it could give eczema research leverage that would amplify federal funding and/or increase the rate at which practical cures emerge.

I believe in the NEA and so I am dedicating this blog to the purpose of raising $1 million for the NEA to devote to research. I'm hoping that people who are thus inspired to donate to the NEA will mention my blog to the NEA, so I can have some idea whether I'm getting close to my goal.

And ultimately, the real goal is to end eczema.

Fantastic filaggrin article

I'm genuinely excited today. I found something much more interesting than the usual crop of eczema news. In the magazine The Scientist--which has a tradition of features that have a strong strain of narrative writing--that is, story, rather than just a gaggle of facts and jargon--I found an article written by Irwin McLean, a professor at the University of Dundee in Scotland. McLean is the lead author of the landmark papers that reported, first, mutations in the filaggrin gene that cause ichthyosis vulgaris, a dry, scaly skin disorder; and, second, that the same mutations caused (or greatly increased the risk of) eczema.

Please read McLean's article. It is effin' awesome. It's written by an expert and as riveting a read as you'll find anywhere, if you're interested in eczema science.

Here's McLean's explanation of why filaggrin matters:

Filaggrin is crucial for the formation of the stratum corneum, the layer of dead cells at the surface of the skin, and also for the hydration of this crucial barrier layer. People who have mutations in one or both copies of the filaggrin gene produce dry and flaky skin that is permeable to allergens or chemical irritants. When the barrier is broken, foreign material is able to pass through these skin layers. We think that childhood eczema—which usually first occurs within the first few months of life—is an indication that foreign pathogens and irritants have passed through an abnormally porous skin layer, activating a strong allergic immune response, and thus priming the body to react to antigens that it would not normally encounter by this route. Later in life, when the child’s immune system comes into contact with those same allergens, perhaps through the lungs, it reacts aggressively, causing the inflammation in the lungs that results in shortness of breath. In fact, many children with eczema have multiple allergies to house dust, pet hair, and other substances.

McLean tells the story of how he and his team identified the mutations in the filaggrin gene (FLG). FLG is a remarkably difficult gene to sequence and was one of the last to be conquered by the Human Genome Project. It's very large, and contains 10 (or, sometimes, more) identical subunits, which means that if you start sequencing somewhere in the middle, as is done in a shotgun approach (where you sequence a lot of small bits and join them up like a jigsaw) you can't be sure if you're sequencing just one of the subunits, or more than one, or all of them at the same time. "It was as if nature was having a joke at our expense," McLean writes.

The team managed to identify the two mutations in ichthyosis vulgaris-- but then one of the scientists, Alan Irvine, pointed out that many of the patients in the subject group also suffered from eczema, many more of them than were in the control patient group. (It's this kind of insight that drives scientific discovery.) McLean, Irvine, and colleagues ran a statistical analysis on their patient group, which was very small by epidemiological standards--only 50 affected patients, and 200 controls, instead of thousands--and found that the  measure of significance, the "p-value," indicated beyond a doubt that there was a link between eczema and the mutations.

At the end of the article, here's McLean on what's next.

The question now is how to prevent eczema, asthma, and allergies from occurring in patients with the susceptibility mutations in their filaggrin gene. If it were possible to find a cure for eczema in adults, could we also cure asthma, or would it be too late, with the immune system permanently primed against allergens? I would argue that it might at least help. If the skin barrier is not repaired, then the immune system will constantly produce more antibodies in response to allergens that continue to get past the barrier. Stopping that assault may have some beneficial effects. The alternate possibility is that we may need to prevent eczema in young children before they become sensitized. If the latter proves true, would it be sufficient to curb eczema early in life, as the immune system develops? These are all questions we are gearing up to answer...

...We’ve also started to look for ways to help the body replace filaggrin at the cellular level. We are currently searching small-molecule chemical libraries for new classes of compounds that might induce skin cells to produce more filaggrin protein. Results look promising, and we are hopeful that in a few years’ time, new drugs or creams that enhance skin-barrier function will be available to treat these common diseases.

From McLean's biography we learn that he briefly worked at a biotech company, which is good news for us: he probably has some idea of how cures get from the benchtop to market.

I'm going to argue that HERE is where we need to put our money from philanthropic donors. Now that McLean and his team of leading scientists have found these mutations and laid bare the role of filaggrin in eczema, we need to help entrepreneurial scientists translate this research into startup companies or intellectual property that can be licensed to big pharma or biotech companies such as Genentech. THIS, the proof-of-concept stage, is where funding in the area of $100k can make a difference to an academic lab-- the difference between the science turning into real cures, or languishing in the pages of the scientific literature.