Allergies: Better to eat foods than to waste away

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

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

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

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

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

The authors make a number of intriguing points.

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

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

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

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

NIAID lays down the law for food allergies

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Did I mention that you should donate to the NEA?

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

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

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

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

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

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

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

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

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

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

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

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

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

And ultimately, the real goal is to end eczema.

Fantastic filaggrin article

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

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

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

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

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

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

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

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

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

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

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