Tuesday, December 21, 2010

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.

Monday, December 20, 2010

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.

Friday, December 17, 2010

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.

Thursday, December 16, 2010

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.

Wednesday, December 15, 2010

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.

Monday, December 13, 2010

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.

Friday, December 10, 2010

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.

Thursday, December 9, 2010

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.

Wednesday, December 8, 2010

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.

Tuesday, December 7, 2010

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.

Monday, December 6, 2010

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.

Friday, December 3, 2010

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.

Wednesday, December 1, 2010

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.

Tuesday, November 30, 2010

Immunotherapy: a history of histamines

"Winter" here in the San Francisco Bay Area may not be severe by anyone's standards, but there's a definite change in the air that has flipped some sort of switch for me and Voov. It's always been this way, mysterious: changing weather makes eczema worse. Toward winter, it's probably reduced humidity in the air; in spring, there's probably pollen. Can't do much about either! Slather on more moisturizer after November, maybe, but it's not a 100% remedy. And as far as antihistamines go for pollen: completely useless, in my experience.

So here we are, skin suddenly tighter and drier, the red excoriations on our hands and wrists. But neither of us is going through an extreme flare.

I ran out of Eucerin on the weekend, and picked up a jar of generic moisturizer at CVS. You know the kind. It's the store brand stuff stacked next to the Eucerin, and the price tags read "Eucerin: $15.99" "CVS Moisturizing Creme: $9.99." You get what you pay for. The problem is, the cheap stuff may LOOK the same as Eucerin, but it sucks. It's thinner and slippery and wears off fast. I have to relearn this the hard way every six months or so.
* * *
I want to share this review with you. It covers the history of our understanding of how immunotherapy works. The senior author is Mitchell Grayson, the scientist from the Medical College of Wisconsin who gave a presentation on eosinophils at the recent annual meeting of the American College of Allergy, Asthma, and Immunology.

The review is only eight pages including two of references, but it's encyclopedic. It follows immunotherapy all the way from its inception in 1911 (Leonard Noon's paper in the Lancet on injecting hay fever patients with grass pollen extract) to the current day. The authors explain how the therapy has remained essentially the same, but our understanding of how it works has evolved to become ever more complex as scientists have laid bare the secrets of the immune system.

In short: in the 1930s, scientists realized that patients given immunotherapy develop "blocking antibodies" that hinder the overeager allergic response. In the late 1960s, they learned that immunotherapy stabilizes mast cells and basophils and reduces the quantity of histamine released when patients encounter allergenic triggers. In the 1990s, after the discovery that there are at least two subtypes of helper T cells, scientists realized that immunotherapy partially shifts the T cell population in allergic patients from the allergy-related type 2 to the infection-related type 1. And in the mid-2000s, regulatory T cells were discovered; immunotherapy apparently increases the number of regulatory T cells that inhibit type 2 helper T cells.

Over time,  immunotherapy has been refined. With greater understanding of how the mucosal membranes process allergens, scientists developed sublingual immunotherapy, in which the allergens are placed under the tongue and absorbed into the tissue, where they are taken up by dendritic cells. (Straight-up oral immunotherapy, where the patient swallows the substances, is a bust.)

And, for asthma patients at risk of severe allergic reactions, doctors now administer immunotherapy along with the monoclonal anti-IgE antibody "omalizumab." Which is produced by Genentech, naturally, and costs $10,000 to $30,000 a year. I wonder, within the US, which insurance plans cover this, and whether the product is available outside the US. It's relevant to eczema because it appears to be quite effective-- it might become cheaper over time (e.g. after the patent expires) or other companies might develop alternatives to take excess IgE out of our systems.

Monday, November 29, 2010

Badge of honor

At the bottom of the right-hand column you'll notice a snazzy new badge. End Eczema has been recognized! By that fine institution, www.medicalassistantdegree.com. If you click on it, as I did, you'll end up on a page listing nineteen blogs. "Score!" I thought to myself. "A whole host of eczema blogs-- the vibrant blogger community I always knew was out there!"

Unfortunately, on closer inspection, all of the other blogs, if not dead, either have been quiet for months or clearly have no scientific merit. Or any kind of merit. Sigh. Eczema Mom and Cindy: L'eczema blogging community, c'est nous.

But I'll wear the badge with pride, at least until a better one shows up. It's like having a degree in blogging from the University of Phoenix.

Speaking of academic institutions, today I found a syndicated newspaper column in the LA Times online, written by Henry Bernstein, senior lecturer in pediatrics at Harvard Medical School. A reader asks him "what can I put on my 3-year-old grandson to treat his eczema?" According to Bernstein, those of us with eczema can expect to have
  • Dry, scaly skin
  • Plugged hair follicles that make bumps (usually on the face, upper arm and thighs)
  • Swelling around the lips
  • Darkening of the skin around the eye
Dry, scaly skin: check. Plugged hair follicles? Swollen lips? Dark circles around the eyes? Is this how they teach dermatologists at Harvard to diagnose eczema? I'd rather my dermatologist had a diploma from the University of Phoenix. Oh yes, Bernstein does get around to answering the question in the end: you should be putting moisturizer on your grandson. Duh!
* * *
As you can see, I have been inspired by the holiday spirit.
* * *
I learned that the company 23andMe in Mountain View, CA has a special deal out on personal genetic sequencing. For $99 you can send in your spit and find out your risk of developing 175 different conditions. Atopic dermatitis is one of them. If you're reading this, I suspect you already know what your risk is-- but FYI, they appear to be testing whether you possess one of the two common mutations of the filaggrin gene.
* * *
In my last post, I mentioned that another Bay Area company, Anacor, has an interesting anti-inflammatory drug in the pipeline, a boron-based compound. I should have mentioned that I find it interesting because it is most likely not a steroid, and won't have the side effects of steroids-- though it will inevitably have other side effects. I'd like to know how it works and what strength it might be (compared to the US steroid scale).

And something else I'd like to know: is anyone making an anti-ITCH cream instead of an anti-inflammatory? Is anyone addressing itch neural fibers rather than just reducing the blood flow to the skin?
* * *
Here's a story about another experimental drug: this lady, in England, suffered from hand eczema that became debilitating-- affected her right hand so that she could hardly use it for anything, and looked so nasty she had to wear a Michael Jackson-style single black glove. She was put on steroids, of course, and given UV treatment, which did nothing. What appears to have put her eczema in remission is a drug called alitretinoin, which is sometimes prescribed for Kaposi's sarcoma.

What is alitretinoin doing to relieve eczema? I'm not sure. At least it's not a complete shot in the dark for a dermatologist to prescribe: here's a story describing how a clinical trial of alitretinoin in Europe and North America cleared up hand eczema in ~50% of treated patients. I believe hand eczema (on the palms, not the backs) can often be triggered by rubber gloves or exposure to certain metals. A few years ago, I had eczema on the soles of my feet-- I think it was the hot, humid climate of Washington, DC, that was to blame-- and it was intolerably itchy. Denise Hyland has my full sympathy.

Wednesday, November 24, 2010

The holiday challenge begins

Tomorrow in America, the first wave of the great tide of holiday craziness will wash over us-- beginning with the inevitable turkey dinner. I'm not a native-born American, so although I have come to love Thanksgiving, I'm still not used to the idea of the entire month of December being given over to overeating and indulgence. At work, the holiday parties start the Monday after next. It's almost impossible to avoid eating or drinking all kinds of things that trigger eczema: chocolates, booze, spices. More booze. And eggnog. I used to like eggnog--in fact, I still do--but a few years ago, after having had a skin prick test that showed I reacted to raw egg white, I suddenly realized that eggnog has RAW EGGS in it, and that's why I was always scratching like a monkey after a glass or three. (Sometimes the eggnog has booze in it, too.)
* * *
I'm always interested when there's a story in the news about someone with eczema. Here's a recent one from Scotland, about a five-year-old girl in Linlithgow (outside Edinburgh).
Despite being so young, Gaelle, a primary one pupil, has used her experiences of atopic dermatitis to educate her classmates and teachers, who have to help her apply her skin cream and bandages every day at school.

She even used her birthday party to fundraise for the cause.
At five years old, she can't have come up with these ideas on her own. She's got some parents who are taking the offensive. It's a good idea. When the kids in Gaelle's class are older and start to cast about for others to tease, they'll at least have had some hands-on experience with eczema and some understanding of what it means to someone who lives with it, and they may not be so quick to treat her as an alien.
* * *
Another news item: UAS Labs, a probiotics company in Minnesota has won an award for "Probiotic Customer Value Enhancement." Thrilling stuff, you will agree. What caught my attention was that UAS makes five "formulations" of live bacteria for specific conditions, and one of them is atopic dermatitis. What's in the AD formulation? A mix of Lactobacillus acidophilus (the yogurt bacterium) and Bifidobacterium lactis. Both are common gut bacteria, but also common probiotics. UAS worked with a scientist in Ukraine on a study to explore how their formulation might improve AD in kids aged one to three. It's not clear whether UAS funded the study; I expect they did, because otherwise there'd be no need for someone in Ukraine to obtain UAS's formulation. Still, the results of the study--presented at a symposium, not published in a journal--showed that eczema symptoms were reduced by 34% on a standard scale for kids taking the probiotics, versus being reduced 19% for kids taking placebo.

If these results are real, which is not at all certain, then it's interesting to think how intestinal bacteria could help reduce eczema. Are they helping the body digest milk proteins or sugars that would otherwise cause an inflammatory response that, in susceptible people, manifests in the skin? Lactose intolerance is widespread. Perhaps it's linked to milk reactions in eczema. I don't know at this point.
* * * 
And a novel topical anti-inflammatory cream/ointment is entering phase 2 trials in eczema patients. Anacor is a San Francisco Bay Area company that makes drugs based on its trade secret, a "boron chemistry" platform. Phase 2 is VERY early in drug discovery, but it's interesting to watch this sort of thing emerge. They seem to have a good idea of what their drug is doing to reduce inflammation.

I'll be off tomorrow. We may be lucky and hear from Dr. Sib. She's Canadian and had her Thanksgiving about a month and a half ago. Unless she's working the midnight-to-8 am ER shift, what possible excuse could she have for not writing?

Tuesday, November 23, 2010

Sunflower seeds and coconuts-- good for more than eating?

In the email Peter Lio sent me the other day, he mentioned that he is getting excited about the potential of two natural products: sunflower oil and coconut oil. He sent me references to two research papers on the topics.

Since sunflower and coconut oils are both edible, I imagine the risk of adverse effects (unless you're allergic to them) is pretty small. And they're oils, so that means they can work as emollients, and soften the skin and reduce transepidermal water loss. I'd like to know how they work in this dimension compared to commercial moisturizers-- does a lot rub off? (I have a problem with my clothes getting greasy) and how often do you have to apply them?

The most interesting thing is that these oils may have special properties; apparently coconut oil contains a fraction with antimicrobial activity, and in one study with a small number of patients, was shown to reduce Staph. aureus colonization.

Sunflower seed oil may be slightly more complex; or perhaps it's just that in the review paper I read, the authors covered a lot of research considering different aspects of sunflower seed oil. Let's call it SSO for short. The point of review's authors is that SSO is actually good for eczema treatment, but allow me to digress for a paragraph.

/Start digression The main component of SSO is the "essential" fatty acid linoleic acid. The authors point out that linoleic acid can be converted to arachidonic acid, a precursor of prostaglandin E2, which they say is a "known modulator of cutaneous inflammation." Indeed it IS a modulator-- PGE2 is a vasodilator and used clinically to induce erections and hasten birth. The review paper considers pediatric use, though, so let's assume those aren't going to be issues. (I'm just pointing out that you can't vaguely say "oh, this lipid turns into something that is INVOLVED in modulating inflammation," and expect me to rub it all over my skin when the compound concerned CAUSES inflammation.) /End digression

The lead author of the study works at Rady Children's Hospital at UCSD, home to a famous pediatric eczema center, so he's probably not a kook. Let's look at some positive aspects of SSO the authors highlight: a number of studies show that in a 2% formulation, SSO has anti-inflammatory properties equivalent to a "mid-potency topical steroid" and, when used in tandem with an actual steroid, can enable the same effective strength for 25% of the original steroid dosage.

This former grad student has some questions for the speaker.
  • Steroids are related to cholesterol-- is anyone sure that SSO doesn't contain a certain percentage of "natural" steroid that is causing these effects? (And could have the same side effects as an "artificial" steroid?)
  • Is there more than one active component? One or more of the major lipids, or some drug-like compound present at a small percentage?
  • I'd like to see a breakdown of what's in that "2% sunflower oil distillate." The scientists seem to be mixing SSO with a bunch of lipids that are essentially the same thing as SSO, but also adding some nameless "phytosterols" and vitamin E.
  • Who decided that 2% formulation was the ideal composition? And, most importantly, where's the dose dependence data? In drug trials, it's key to show that the magnitude of therapeutic effect increases as you increase the dosage of drug-- that indicates that it's the drug that's making it happen, and not something else you hadn't considered. I don't see any mention of dose dependence in this review.
OK, I've evidently developed a skeptical reaction, which I honestly didn't have to begin with. Sunflower seed oil-- I'm going to need some more evidence that there's anything behind the claims. It's not going to be anyone's miracle cure, but there's always the possibility that a natural product is hiding some magical ingredient.

Monday, November 22, 2010

Aveeno stonewalls; and introducing eosinophils, the "riflemen" in your skin

So I wrote to Aveeno the other day, asking them two very simple questions:
  1. What makes the Eczema Therapy line different from any of their umpteen other moisturizers?
  2. What data can they show to prove that it works?
I found out that Aveeno is owned by Johnson and Johnson, and that, despite Aveeno's friendly Facebook video, J&J is as terrible at customer relations as any giant corporation.
Answer #1:
...the Aveeno® Advanced Care™ Moisturizing  Cream is different in these ways:

-Pure oat essence and natural colloidal oatmeal to soothe skin
-Ceramides to help enhance skin's ability to retain moisture
-Plus moisture-rich oat oil
However,  this product has since been discontinued.
Not particularly helpful, since that wasn't the product I asked about. I wrote them again, repeating my original question. We'll see what they say. The active ingredient in the Eczema Therapy lotion is 1% colloidal oatmeal. Hardly revolutionary. Is it any different from anything else Aveeno puts out? Probably not.

Answer #2:
We are very sorry, but our company policy prohibits disclosing this type of information. Most of our research, marketing and sales information is proprietary, as is information regarding our ingredient percentages and formulations of individual products.
So: none of your business.

I did call the FDA to see if there were any instances on record of an official FDA warning letter being sent to Aveeno (recall, Peter Lio told me Aveeno had come out with this line a few years ago, and got their hand slapped because they were making an unsubstantiated therapeutic claim).  I was shuttled from the cosmetics division to the drug division-- colloidal oatmeal is classed as a drug, I found out, with the magical property of "skin protectant." There are no warning letters on record. I'm guessing that perhaps there was some low-level communication from the FDA to Aveeno that resulted in them listing colloidal oatmeal as the active ingredient.

The ridiculous thing is that someone at some point had to register oatmeal as a drug, which must have involved all kinds of safety trials.

* * *

Last week, you may recall, saw the end of the annual conference of the American College of Allergy, Asthma, and Immunology. On the Saturday before last, there was this session in the afternoon called the "Great Atopic Dermatitis Raft Debate." I have now found out what this was about, or more specifically, what "raft" is doing in the title. From the conference brochure:
Premise: Experts involved in atopic dermatitis management are adrift in a life raft. There's enough food and water in the raft for only one to survive, and the surrounding waters are teeming with sharks. Each expert has exactly 15 minutes to make his case. Come and see who gets tossed to the sharks!
This explains why sharks feature so prominently in the Powerpoint of Mitchell Grayson, MD, one of the presenters. I wrote to all four professors in the debate, asking if they could send me their presentations and save me paying $350 to the ACAAI (now there's a posse of sharks) for the conference DVD. Only Grayson obliged. So I declare him, by default, the winner-- we toss Mark Boguniewicz, Donald Leung, and Lawrence Schwartz off the raft.

Grayson represented "eosinophils" in this epic tussle. Eosinophils are a type of white blood cell. My PhD topic had an immunological focus (helper T cells) but I really never heard diddly about eosinophils, so I was excited to go through his presentation. Let me share the gist:

On the battleground of eczema, eosinophils are the "riflemen," according to Grayson.

Eosinophils are, he argues, the cells most responsible for eczema. (Keep in mind that he was trying to win a 15-minute debate.)
Eosinophils, triggered through a signaling chain that begins with mast cells and goes through T cells, are the ones who "shoot" pathogens, destroying them with reactive oxygen species (e.g. peroxides) and "cytotoxic granules," aka poison. We'll ignore the fact that history usually holds the generals responsible for what the army does in war, although recent events at Gitmo show that we may not have enough perspective on that conflict yet.

Activated eosinophils are found in the middle layer of skin in patients with eczema. In normal skin, eosinophils have no business being there. Some scientists think that eosinophils contribute to skin irritation by releasing their toxic payloads. Here's a microscopic view of an eosinophil, from Grayson's Powerpoint:
You can see a cytotoxic granule highlighted. Some evidence that skin eosinophils may play an important role in eczema: urinary levels of eosinophil products are proportional to the severity of eczema; treatment of eczema with tacrolimus and pimecrolimus reduces the number of skin (but not blood) eosinophils; reduction of blood eosinophils has no effect on eczema. One experimental mouse model develops eczema only if eosinophils are present.

So there's a lot of circumstantial evidence against eosinophils. Our real question: OK, say you prove eosinophils are the key-- how can we target them to prevent eczema?

On that, Grayson has no answer. We can forgive him, though. It seems that dendritic cells and adhesion molecules are really what he specializes in.

Friday, November 19, 2010

The secret powers of oatmeal

I'd like to ask you a favor. Since the purpose of this blog is to raise $1 million for eczema research-- through a cunning plan the details of which will be revealed, and if you find out, please tell me-- I'd appreciate it if you could link to this site and share it with your friends. This will raise the blog's Google profile. At the moment if you go to blogsearch.google.com and type in "eczema blog," Google returns a lot of pretty useless sites. (Mind you, Priya Mulji's blog ranks highly--she sometimes has a good personal take on eczema, although not from a scientific angle.) To attract the attention of potential donors, I want to get this site ranked higher. I'm not asking YOU for money, unless you can write a check for $100,000. I just want to reach blue-blood philanthropists affected by eczema who may not realize they could make a difference.

About Aveeno's new "Eczema Therapy" product line, now touted on their Facebook page-- writing about it yesterday, I wondered what it was about colloidal oatmeal that makes it such a fantastic ingredient in these various powders, bars, lotions, etc. that Aveeno manufactures. I wrote to Peter Lio, MD, an associate professor of dermatology and pediatrics at Northwestern University. Lio gave a presentation at this summer's NEA Patient Conference in Chicago, and covered skin pH, cleansers, and moisturizing, so I figured he'd have an answer. And he did. Let me quote his email, since it is so readable and packed with information:

About the Eczema Therapy line:
They've actually been out for a few years, initially as Aveeno Eczema Care, then the FDA slapped their wrists for putting a disease name on a product without evidence to back it up... so they had to pull it and it was then called Aveeno Advanced Care... and now they've finally got it back up with some data, calling it Eczema Therapy.
On oatmeal:
Oatmeal is pretty interesting and does seem to have some specific anti-itch and anti-inflammatory properties of its own. "Avenanthramides" are thought to be the "active ingredient" in them (but it is probably a whole lot more complex, as with many plant products).
Aventhramides, he says, act to reduce cellular levels of NF-KB, a molecule that triggers protein production in the immune response-- so they could reduce inflammation in this way. From what I know, NF-KB seems to be involved in a lot of processes, so there must be more going on, and Lio elaborates:
Cells treated with avenanthramides showed a significant inhibition of tumor necrosis factor-alpha, a powerful inflammatory cytokine. They have also found direct anti-itch effect with these substances as well. (Reference)
He thinks Aveeno may be going too far, chasing novelty for marketing purposes: 
[The] Aveeno line...is such a complex lineup of products and they keep moving things around and changing things!  If I tell a patient about an Aveeno product, they go to CVS or Walgreens and find 2 shelves of different types of moisturizers... Active Naturals, Positively Radiant, Clear Complexion, Positively Ageless, Nourishing Refresher...I just wish they'd put their best foot forward and make the best one they can make. That's why I love CeraVe so much.
I agree. Less is more. Aveeno confuses me with their offerings. At least their shaving gel is back on the market, after a hiatus of frickin' MONTHS in which I had to shave using an Aveeno bar or whatever fragrance-free shave gel I could find at CVS. (Walgreens: still in the Stone Age, carries no fragrance free shave gel.)

Lio also has some interesting ideas about other natural emollients, which I'll share in a future post.

Remember the ACAAI meeting in Denver? (Peanuts in schools; anaphylactic shock via sex.) I did get in touch with Mitchell Grayson, one of the four pugilists in the Great Atopic Dermatitis Raft Debate. He was in the "eosinophil" corner, and he sent me his Powerpoint presentation. Now I know a lot more about eosinophils. And so will you, if you read my next post.

Thursday, November 18, 2010

Aveeno rolls out new line of eczema moisturizers

In my newsfeed today I got a press release from Aveeno-- apparently they have just rolled out a new line of moisturizers especially for kids and adults with eczema. In fact, you can find a promo video on Facebook. In the video, Suzy Deprizio, a brand manager for Aveeno, talks about how she's been involved in developing the moisturizers (or developing the marketing strategy? Not entirely clear to me) for five years, and how she found out that her young daughter had eczema. She also offers a few tips, none of which will surprise you if you live with eczema: clip fingernails, etc. It is interesting to know that there are people at Aveeno who have a personal stake in the products. Aveeno's definitely an example of a company whose products benefit society. Looking forward to trying out the new creams!

On the topic of moisturizers & skin barrier, there is a good article in The Advocate, basically a transcript of a presentation by Peter Lio, MD, at the 2010 NEA Patient Conference in Chicago. Lio makes a few interesting points. One is that traditional soaps-- say, Ivory, or something that you might make yourself from lye and rendered fat if you're under the impression that "pure" or "simple" equals better--are harsh on the skin. Quite apart from their surfactant properties, when mixed with water, they increase the pH, making a strong alkaline solution. Why is alkalinity bad? Because the skin's natural pH is slightly acidic.

When the skin becomes more alkaline, the conditions favor the action of natural enzymes called serine proteases, which break down the bonds between skin cells and chew up other enzymes that produce fatty molecules called ceramides. Ceramides, in the right balance, are essential in creating a good skin barrier. So traditional soap not only removes these lipids from the skin, but reduces the skin's ability to replenish itself. You can find a good review of the skin barrier in eczema here.

Lio also discusses commercial moisturizers. He says (and I've found) that pure petroleum barriers such as Vaseline aren't very useful. They do indeed keep water in the skin, but as soon as they rub off, they don't. When I put Vaseline on eczematous skin, the benefit seems to wear off within minutes. "Right now I would say it's nice to look for something that contains ceramides," Lio says.* We're using CeraVe on Voov--it contains ceramides--and it seems to be working very well. The stuff is hella expensive though. It makes Eucerin look cheap. But I am going to start trying it out on my hands to see if it makes any difference. (I know, I know, Eczema Mom, you advised me to try it a while ago. But we all get attached to our daily routine and it's hard to change.)

*So do these Aveeno products have ceramides? If not, why is colloidal oatmeal so good for skin? Will investigate.

Tuesday, November 16, 2010

MRSA-- like a sourdough starter

An item to emerge from the American College of Allergy, Asthma, and Immunology meeting in Phoenix this week: if someone has an extreme food allergy, you can give them a reaction just by kissing them.

Bizarre, but makes sense, and highlights how sensitive our immune systems can be. If tiny amounts of allergen can cause such severe trouble, it seems more plausible to me that the broken skin of eczema can expose young children to allergens that might sensitize the body for life.

I've read through The Advocate once now (get this-- that picture of the torn-up foot on page 5-- I read that page while I was eating dinner, that's how DEsensitized I am to eczema) and, once again, I appreciated it on several levels.
  1. I feel better by comparison, because some people out there evidently have it much worse than me and my daughter
  2. I feel like I belong to a wider community facing the same challenges we do
  3. I'm interested to hear advice from leading scientists in the field on day-to-day therapy and some of the more advanced/extreme options
My god, the poor kid, Joanna Hamilton's son Jonah, with MRSA. I can relate to him about the food (my mom says at one point she was only feeding me carrots and bananas, and my nose turned orange) and the scratching (my own feet and Voov's have at times looked like that photo) but not the MRSA. That is some bad shit. From what I've heard, the more you can stay out of the hospital, the better chance you have of avoiding it. But what about the doctor's office? When you have a young child, you are in the doctor's office virtually every week getting some rash or cough or weird eye tic checked out. Is MRSA in the doctor's office too? I'd appreciate knowing.

Earlier this year, Voov had some terrible staph all over her hands. She was crying all the time and her hands were all blistered and bloody and crusty and you couldn't even see a spot of decent skin. Naturally, we were on vacation. We got back home and Voov went on some antibiotics and her skin cleared up all over her body. Then, bingo, I suddenly developed a staph infection, a lovely one on the back of my head. It cleared up by itself, fortunately. In these six-kid families that have multiple members with eczema, they must pass an infection around for months, keeping it alive like a sourdough starter.

Monday, November 15, 2010

An ill-advised comment on peanuts

Upon arriving home this evening I was not only welcomed by Hidden B (torrid spousal kiss), Voov (loud acclamation from high chair), and Shmoop (whiny complaint from the floor, where he was lounging, practising to be a teenager) but also, on the kitchen table, this quarter's issue of The Advocate, the NEA's house publication.

The Advocate is best savored at leisure, like a fine malt whisky, so I'll save my review for future posts. Today I want to mention that the annual meeting of the American College of Allergy, Asthma, and Immunology is still ongoing in Phoenix. It was at this meeting that, on Saturday afternoon, Donald Leung and three other immunology heavyweights engaged in the knock down, drag out brawl known as the Great Atopic Dermatitis Raft Debate. The four presenters each argued that their pet cell types (keratinocytes, T cells, etc.) play the most important role in eczema. Man, I'd like to know what they said, but the event wasn't webcast. I did find out, however, that the proceedings of the entire conference were videorecorded and are available on DVD-ROM-- for me, at the low low price of $340.

Maybe there's some way to get just the session I'm interested in, but it'd probably take more effort than I can spare. (I was also informed that audio recordings might be cheaper... but who's going to pay a hundred dollars for a podcast when these scientists are probably leaning heavily on Powerpoint diagrams?)
* * *

The ACAAI meeting has been in the news, because the president of the whole shebang has gone on the record saying that people take peanut allergies too seriously. I'm sorry, but this immediately discredits his expertise. I know that latex and peanut allergies can be life-threatening; and their incidence is increasing. It doesn't matter if the incidence is low (~0.5%)-- in a school of, say, 1000, that means you have five kids who could potentially die if one of their classmates (it is clinically proven that 100% of kids are capable of being idiots) thought it might be funny to see what happens if Johnny takes a bite out of the wrong sandwich.

I know someone who died of an asthma attack; I also know someone whose wife nearly died from a latex allergy. I'm no expert, but I think peanuts probably pose the same caliber of problem.

This is one area in which America's "sue first, ask questions later" culture will work for the good of society. I can't imagine a school principal revoking a peanut ban because Dr. Bahna said so. Fewer peanut bans may get enacted, though.

For the record, I loves me some Snickers, and I eat PB&J every single day. But I'd quit on the spot if someone's life was endangered.
* * *
A blog post worth checking out: in which a UK citizen of east Indian descent talks about her teenage experience with eczema. For me, too, eczema came on with a vengeance not long after I got interested in the opposite sex. I didn't develop big boobs to compensate, as she did-- but, on reflection, that's probably a good thing.

Friday, November 12, 2010

Teenage years are hard

Not the happiest news today, I'm afraid: some poor kid in Manchester, England apparently committed suicide after being taunted at school about his eczema.

It's hard to be a teenager. Many kids are insecure--they think that others think they're not tough enough, or not cool enough, or whatever-- so they bully and torment kids who don't fit in. And it's easy to single out the boy with the funny rash.

Of course there could be more to this story. The boy may have been suffering from clinical depression, which is distinct from general teenage angst. But who among us adults doesn't still keenly recall every casual remark that wounded us during those years?

I'm lucky. Although I definitely had eczema all the way through high school, nobody made a habit of jeering at me for it. (Instead, they jeered at my accent, haircut, trouser cuffs, and Bryan Adams cassettes, among other things.)

We should tell kids with eczema that life does get better. Your eczema may not improve, if you're one of the unlucky 2% or so. But past high school, you're not trapped in the zoo any more; the cliques aren't as intense, because people have little to gain by making you feel bad. The more life experience people have, the less they care about how your skin looks. And if you can feel confident in yourself, it shows on the outside.
* * *
An important conference opened yesterday in Phoenix: the annual meeting of the American College of Allergy, Asthma, and Immunology. There's a particularly interesting session on Saturday from 1:30 to 3:00 pm. It's titled "The Great Atopic Dermatitis Raft Debate: The Greatest Role in the Pathophysiology of AD." (I don't know what "raft" means here.) It's basically a four-way mano-a-mano between presenting scientists, each of whom is claiming that the cells THEY study play the most important role in eczema. Our good friend Donald Leung (head of the Atopic Dermatitis Research Network) is in the T cell corner. He evidently wrote the abstract, because it says "Upon completion of this session, participants should be able to... describe the scientific evidence that supports T cells as playing the key role in causing AD."

Which is amusing, because the more I read about eczema, even in articles written by Leung, the more it emerges that eczema arises from a barrier defect in the outermost layer of the skin-- a defect in keratinocytes. (He does nod in their direction, saying keratinocytes have a "critical" role, but not the KEY role.

I've snoozed through many an academic conference presentation, but I'd sure like to be at that session! It'd be like Iron Chef, only immunology.

Thursday, November 11, 2010

Eczema under the guns

Today, depending where you are in the non-German Western world, is Remembrance Day (British Commonwealth), Veteran's Day (US), or Armistice Day (France & Belgium).

My father's father, Titus, served in the 48th Nova Scotia Highlanders in WWI. I've seen a map of his regimental movements and although there were a number of famous place names on the path, I remember only one: Passchendaele. I think Ypres might have been there too. Old Titie, as my dad calls him, apparently used to freak out whenever someone burned the toast at home, because the smell reminded him of poison gas.

Titus was the one grandparent of mine who had eczema. His itch was legendary. "Old Titie was always scratching," my dad says. (I don't remember Titus; he died when I was five.) I don't know whether the stress of being under bombardment would exacerbate eczema, or distract the mind from itch, and with any luck I'll never find out. Eczema must have made life in the trenches even worse. Titus, we can't imagine what you went through. Thank you.

These days, eczema is a condition that disqualifies you from service in the US military. The reason: in 2007, a soldier vaccinated against smallpox gave his two-year-old son the often lethal condition eczema vaccinatum. An all-out medical effort saved the kid. Now, one can understand why eczema disqualifies you from active service: it would make sense that all service members have to be vaccinated against smallpox, a major biological weapon; and the military would face a major problem if soldiers, etc., refused to be vaccinated because they or their families might die from eczema vaccinatum.

The military therefore is only ruling out about 3-5% of recruits, is my guess. The crucial question is whether you've been diagnosed with eczema after the age of 9. I'm not sure what the precise number is, but about 20% of infants get eczema, and only 2% of adults continue to suffer from it.

I do think that we can look at the bright side of the smallpox/eczema question. It's a point of leverage for us. The US government spends a lot of money on the military, and probably wouldn't mind spending a few hundred million more. The Atopic Dermatitis Research Network was given $31 million to study MRSA and other infections in patients with eczema-- but the initial request-for-proposals was actually aimed at studying eczema vaccinatum. It wouldn't hurt to make our concerns about smallpox vaccination widely known; we could attract major funding. Eczema infection researchers might discover powerful new antibiotics, or other ways for us to protect ourselves from infections such as MRSA.

Wednesday, November 10, 2010

Eczema Haul!!!

An End Eczema first today: let's look at a video. As I've said before, this blog is going to be light on photos and such because eczema doesn't make the most attractive visuals. And video? Well, this one is an exception. It's kind of fun. The girl has decided to show us all the panoply or arsenal or whatever of the products that she uses daily to treat her eczema. She's titled her video "Eczema Haul!!!" --must be some new slang term I haven't heard of.

Easy to tell that she's American: well, first, her accent, but if you hadn't registered that, "I don't have insurance" is a dead giveaway. Let me be perfectly clear. I live in the U.S., but I think it's barbaric that this is the only first-world country without universal health insurance. Imagine having eczema and getting a staph infection and wondering whether you ought to go see a doctor because it might cost too much. For one thing, every infection that unnecessarily goes too far puts other people at risk of being infected.

Here's the video (she's disabled embedding).

A couple interesting points. She's obviously very keen on Aveeno. So am I. It's a great company with great products, and the Daily Moisturizing Lotion with dimethicone (a rubbery sealant) is almost the best I've found. The shaving gel is awesome, although a while back they were having manufacturing problems and you couldn't find it in stores, so I've been using some fragrance-free Edge. But you can't go completely Aveeno. I tried Aveeno shampoo and found it little better than ordinary shampoo,  leaving my scalp drier than the Mojave. Here's my secret: tar shampoo, rinse, and then, rubbed into the scalp, some jojoba oil.

Ironically, jojoba grows in the Mojave.

Toward the end she pulls out a bottle of vitamin E capsules and touts its benefits to people with skin diseases. "Vitamins are good for you, period, people." I am not so sure. I confess to taking a daily multivitamin (mostly for the potassium-- I get muscle cramps sometimes), but all that I read about eczema tells me that the way to a happier you is to avoid problem foods rather than take any miracle nostrums.

To quote an impeccable authority, Wikipedia:
The consensus in the medical community is that there is no good evidence to support health benefits from vitamin E supplementation, yet there is strong evidence that taking more than 400 IU of vitamin E per day for extended periods increases the risk of death.
I like to avoid death, myself. It's something that, according to the prophet Mohammed, even black cumin can't cure.

Something I forgot to relate after my trip east to the science writers' conference this past weekend: there is a new book just out on MRSA. Superbug: The Fatal Menace of MRSA. (The author, Maryn McKenna, was on a panel discussing how to publish a popular science book.) I'm not saying you should read it--even the website gives me the willies--but it sure looks like the comprehensive resource on the emergence of this medical hazard that is of concern to everyone with eczema. Perhaps Dr. Sib can give us her perspective on MRSA, what it's like to deal with it in the hospital.