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.)

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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.

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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.

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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?

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.

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:

Essential ACTIVE NATURALS®:
-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.

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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.

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.

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.