Behold the thistle

You may notice the blog has a new look. "What's a frickin' thistle doing in the header," you may ask. "Does this guy think he's Scottish or something?"

Och no. There's no great significance to the thistle. I just wanted the blog to look more interesting than the basic template. I wanted some image that conveyed eczema in the abstract. The real thing isn't very attractive--if you have it, you know what I'm talking about. So I considered some photos of scratched glass, metal, etc-- distressed material. All too grim or industrial. The idea was not to be negative.

The thistle-- it's kind of pretty, no? But prickly as hell, and can scratch you up. "Prickly" also nails how I feel when I've got a flare-up. I'm irritable, anti-social, and snap at my loved ones. Maybe I'd be a curmudgeon without the eczema-- the point is moot, since it's a part of me and always will be.

Filaggrin, I love ya

I wasn't going to post today-- a bit worn out after taking the kids to a Hallowe'en party and trying to keep Voov (wearing cute flower costume, for the second year) from eating soup and noodles, which are off-limits due to her food restrictions, while trying to keep Shmoop (wearing cute lion costume, for the third year) out of the desserts. Successful with the soup & noodles. Less successful with the dessert. And so, while Voov sits placidly in the bath, Shmoop has a giant screaming and kicking fit as he comes off his sugar high, and must be manhandled to bed.

But I just can't stop wanting to learn more about filaggrin. It's my protein of the month. Here's something else I found today: a 2009 review of the role of filaggrin in atopic dermatitis. (Several studies have positively linked two mutations in the filaggrin gene to a significantly higher risk of eczema.)

So: as I wrote last Saturday, filaggrin is this protein that skin cells start to produce as they move along the treadmill from the inner zones of the skin to the stratum corneum. When the skin cells get to the stratum corneum, filaggrin gets chopped up into short bits called peptides, and these peptides grab hold of the inner keratin skeleton of the cell and pull it all together, flattening the cells. A loss-of-function mutation in filaggrin means that your skin's outer layer is defective and, from the very first, it lets in many more pathogens and allergens than "normal" skin-- which may overstimulate the immune system and cause you to develop chronic allergies.

And now, in the 2009 review (which is a year old, so more has been learned since then) I find that filaggrin is no one-trick pony. It's more than a keratin scrunchie. Within the stratum corneum, the filaggrin peptides get progressively degraded and altered unto a mix of amino acids that, along with some ions, is called the "natural moisturizing factor." The natural moisturizing factor is, basically, your own Eucerin, and prevents water loss; it's also slightly acidic.

So when you have mutated filaggrin, not only does it mess up the structure of your skin cells, but it doesn't get processed into moisturizer, and your skin pH is too alkaline-- which has been reported to affect the composition of your T cell populations in the skin, and lead to inflammation.

Cool!

In the last paragraph of these papers, the authors always say something like "this work could lead to targeted intervention and therapy." (They have to, to justify more funding.) At some point, we, the funders, must ask: where's the beef? Tell us how this research is going to lead to therapy. New drugs? How exactly will they be discovered? New emollient strategies? Who's formulating them? And is there going to be any relief for adults who are already well along the atopic march?

Sublingual immunotherapy: why not

Interesting post today on One Mom Against Eczema. Cindy brings something called "sublingual immunotherapy" to our attention (doesn't say she's signing up for it, though).

Immunotherapy was originally done by injection. In the sublingual version, which is apparently used in some European countries, Italy in particular, a doctor (or "wellness practitioner," I suppose) puts a droplet of solubilized allergen under your tongue. You process the allergen and the idea is that your immune system, after a controlled overdosing, becomes tolerant of it--in the same way that our immune systems are generally tolerant of self-antigens.

Our bodies have the ability to become tolerant of allergens, it would appear. I am not familiar with the mechanism (time to dig out my copy of Kuby) but evidently I'm in the company of the medical profession; otherwise this type of therapy would be more successful and, you'd think, approved by the FDA.

SLIT, as those in the know call it, isn't approved by the FDA. That doesn't mean it doesn't work in some cases, or couldn't work in more cases if the dosage, formulation, etc., were optimized. (It does seem to me that SLIT would only work for you if your eczema is primarily due to one allergen.) Many FDA-approved treatments don't work or have nasty side effects. And sublingual immunotherapy, although perhaps less effective than the kind that involves a needle, does no harm to most patients (see: Hippocratic oath). Mind you, don't be the one who goes into anaphylactic shock.

So, I say, go for it, if you have the money to spare-- your insurance won't cover it in the U.S.-- and good luck. That is my attitude to eczema therapy and I've applied it to myself over the years. For example, my dad, a globe-trotting geologist, came back from Morocco with a small bottle of black cumin oil. He'd been in some street bazaar and had told a fez-wearing purveyor of unguents (see: wellness practitioner) that his son, who lived in the U.S., had always suffered from eczema. The merchant advised him that he had a guaranteed cure: "huile de nigelle," or black cumin oil. I think it's this stuff.

Read that Wikipedia entry. There's a quote from the Prophet Mohammad.

"Aisha has narrated to me that she heard the Prophet saying, 'This black seed is healing for all diseases except As-Sam.' 'Aisha said, 'What is As-Sam?' He said, 'Death.'"

It sure sounds like black cumin ought to work for eczema. (For "death" see: disease to end all diseases.)

For one week, I rubbed black cumin oil on my eczematous patches on one side, and left the other side untreated. No effect, unfortunately. It could be that it doesn't work on atheists.

Big genetics

Genetics is all pretty abstract until you find out something about yourself. I only know one thing for sure about my own genome-- I have one copy of the most common mutation for cystic fibrosis. I found this out when Hidden B and I had prenatal screening done about four years ago. The estimated chance of having this mutation is about 5%, so I was unpleasantly surprised. I'm defective! (And each of my kids has a 50% chance of being a carrier.)

On the genetics front, big big news today, although I didn't see anything appear in a major outlet. Maybe I missed it-- more likely is that the news was too complex and not attractive enough for the average reader for newspaper editors etc. to assign the story to reporters.

You'll find decent writeups at Nature News and GenomeWeb. A gigantic international research coalition, the 1000 Genomes Project (nearly as many authors as genomes) published a paper in Nature describing how they sequenced about 880 human genomes. I'll leave out the details, which, frankly, are lost on me, but the point of the work was to get a handle on how our DNA varies from one human to the next. An astonishing quote from the abstract:

"On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders."

Hoo boy. The authors are saying, in essence: each of us is a factory reject. If we each carry 250-300 genes that ought to work but don't, imagine how much redundancy is built in. If a gene is broken, there are others to compensate for it.

This is why it's so hard to find connections between single genes and diseases. It's why scientists think it's a big deal to find that about 20% of children with eczema have loss-of-function mutations in FLG, the filaggrin gene--because 20% is a large number! (Before I studied molecular biology, I would have thought scientists would only care about mutations that were found in, say, 75% of patients with a given condition.)

And EACH of us has 50-100 variants that put us at higher than average risk for a random grab bag of inherited conditions. Tay-Sachs, anyone? Alzheimer's? If you ask me, there's no need to extend the human lifespan. I don't need to discover how many weird things I might develop if I live past 85.

A much lower-profile item: some journal called Nature Precedings (appears to be a catalog of NIH project summaries) reports an ongoing project of interest to you and me: "Skin Microbiome in Disease States: Atopic Dermatitis and Immunodeficiency." Julia Segre and Heidi Kong at the NIH are studying patients with eczema and two immunodeficient conditions to profile the populations of bacteria and other microbes that live on our eczematous and non-affected skin--and in our nostrils! (A while ago, I don't have the reference, someone discovered that nasty bacteria hide out in our nostrils. So stop picking your nose.)

Antibodies, parasitic worms, and cures

Funny vignette: home from work today--I have to bike up a steep hill to get home, and then I'm always hot and sweaty, which triggers the itch. I'm sitting on the floor leaning against the couch scratching the backs of my knees. Voov toddles over and helps me scratch. Shmoop joins in too-- all three of us scratching away at my legs.

Thanks, kids. Though scratching is a department I usually don't need much help with.

I've been reading up on the genetics of eczema. When I've managed to get my head around the subject I'll try to write about it. Suffice it to say that filaggrin is only part of the whole picture, which is complex enough that this picture doesn't do it justice.

In the academic literature, eczema is referred to as "atopic dermatitis" (AD). I always thought this was disingenuous on the part of doctors, to use fancy words that mean the same thing as plain words, in order to maintain the illusion of expertise. "Dermatitis" obviously means "skin inflammation," and I assumed "atopic" meant "we don't know what the hell causes it." (Now I know that would be "idiopathic.") A Google definition search reveals that "atopy" actually has a specific meaning: "allergic hypersensitivity affecting parts of the body not directly in contact with the allergen." Who knew?

Anyway-- eczema, or AD, covers a whole spectrum of disorders. I would like to be as clear on this blog as possible about what I mean by eczema and how it might be cured. You might be interested to know, for example, that two major types of eczema have been identified: "extrinsic" and "intrinsic." Extrinsic AD affects 70-80% of adult patients and involves high levels of circulating IgE antibodies and reactions to environmental allergens. The remainder of adult patients have intrinsic AD, which is defined as the kind that DOESN'T involve high IgE levels or allergies.

IgE is one of five antibody types. IgE is the kind involved in allergies-- when mast cells and basophils bind IgE, they release histamine, which triggers inflammation. IgE is also, somehow, protective against parasitic worms. It could be that those of us with eczema are descended from a population that was under severe evolutionary pressure from parasitic worms. These worms are no frickin' joke-- look up "elephantiasis" or "river blindness" if you can stomach the photos. I don't know about you, but I'd rather have eczema.

I'm guessing that I and my family have extrinsic AD. Naturally, that's the kind I'm interested in!-- but, knowing all too well what it's like to live with eczema, I'd like to see all of us cured.

I'm not naive, either-- I know eczema is fiendishly complex and there's no cure at the moment. It may turn out that we won't see a cure for hundreds of years. It may turn out that the only way to prevent eczema is gene therapy in embryos. It may turn out that you can reduce symptoms dramatically by rubbing your baby with a certain type of protective cream to prevent allergen entry through the skin, and that if you do this during a certain time window, the protection will extend to adulthood. It may turn out that we can't fix anything fundamental, but that we can turn off itching and scratching by using some miracle drug that gets discovered completely by accident. (And, likely, the drug will only work for a certain fraction of people-- but maybe we can identify them by genomic screening.)

It's haircut time!

Fingernail trimming tonight for Voov before her bath. The usual circus of book-reading to distract her, and Shmoop crowding in, blocking out the light so Hidden B can't see well enough to trim off the sharp little edges with which Voov mangles herself. Her skin hasn't been too bad of late, but she's got a patch of eczema on her torso that she was scratching away at with whatever hand wasn't being trimmed.

I read somewhere that infants with eczema exposed to emollients containing peanut protein were at higher risk of becoming allergic to peanuts. The Derma-Smoothe oil we use on Voov contains peanut oil, according to the ingredients. But apparently the proteins have been denatured-- by heat treatment?--or broken down somehow so that they are not allergenic. That's what Hidden B told me when I brought the matter up. The dermatologist said that she'd even applied Derma-Smoothe to a kid with a peanut allergy and seen no reaction. Now that takes some cojones. Why is the manufacturer using peanut oil? It must have some remarkable lubricating properties.

My big achievement of the day was getting a haircut. I'm at the age when my head is only really growing hair around the sides and the back, but you still have to get it cut every once in a while if you don't want to look like this guy.

Inconceivable!

Getting a haircut for me is a matter of timing. I have to do it on days when eczema isn't running rampant on my scalp. (It favors the back of my head.) Sometimes put off getting a haircut for weeks because 1) I've never been keen on letting anyone look closely at my scabs and 2) I've always thought a barbershop would be a fine place to pick up an infection. Sometimes you see barbers take those scissors from the jars of blue sterilizing fluid, and sometimes they just buzz your head with clippers that most likely were just on some other dude's head a few minutes ago. I get my hair cut in downtown San Francisco, which about thirty years ago was where AIDS first broke into the news. Always makes me nervous.

This morning I realized my head was an eczema-free zone. And I was getting shaggy in back. So off to SuperCuts at lunch.

I used to cut my own hair-- well, buzz it really-- but in my current job it isn't an option. Wouldn't look good if I missed a spot, as I've been known to do. Last time I went to a barbershop near home I got some gloomy lady who, besides boring the hell out of me talking about firearms, told me that the guy whose ass was responsible for warming the chair I was sitting in had had a fungal infection all over his head. It was a total Seinfeld situation. She told me that sterilization was priority #1 for barbers. I wanted to leap out of the chair and run screaming from the shop, but didn't want to make her feel bad. I got the haircut. It was no better or cheaper than the one in San Francisco.

So, the moral of the story? Maybe I ought to flatter Hidden B that she's got mad styling skillz.

A genetic origin of the demon itch

One problem with writing a blog is that you write each post separately. It's hard to keep a grand plan in mind and so, even if you think you're focused enough (e.g. eczema research and what it's like to live day-to-day with the condition) you keep getting buffeted around by the news of the day. Such as that PLoS ONE report I wrote about on Thursday.

Hidden B tells me I ought to follow up on some of the promises I made earlier on-- such as to look more deeply at filaggrin and heritability-- and that this would make for a less disjointed read. What Hidden B wants, Hidden B gets.

Two journals in particular have begun to emerge for me as great sources of information about genetics, allergy, and eczema research. There's the Journal of Allergy and Clinical Immunology, of which Donald Leung is the editor. Leung is the scientist leading the Atopic Dermatitis Research Network, funded by $32M from the NIH. So it's no surprise that his journal publishes some good, relevant research. I've read a few papers from the journal and have been impressed by the quality of the work and the writing-- and, believe me, you can't say this about every journal.

Look up "filaggrin" in Wikipedia. The first reference for the entry is a paper from J Allergy Clin Immunol. It's a great introduction to filaggrin and how it may be at the root of a large number of family-related eczema cases. This paper (Weidinger et al.) references a number of papers from Nature Genetics; the most important ones are from 2006, when, it appears, two overlapping groups reported finding loss-of-function mutations in the filaggrin gene that are associated with eczema. Filaggrin looks guilty to me. (See fascinating blog entry in the Nature system.)

But, as anyone with eczema knows, it's a complex condition; the underlying science appears just as complex. Weidinger et al. analyzed 476 German families: from each family, the parents and one child with AD. I haven't digested the paper fully; but of the 476 kids, roughly one-quarter had one of the two known loss-of-function filaggrin mutations. So there are evidently other molecular causes of eczema. Maybe there are yet-unmapped filaggrin mutations. Maybe there are mutations of other genes that screw up the same processes as mutated filaggrin. There are probably many, many paths to the same end.

What is filaggrin? It's a protein product of the FLG gene on the q-arm of chromosome 1. The gene itself is complicated, which is why scientists took a long time to sequence it. I look forward to learning more!

FLG is expressed as profilaggrin, a larger protein, in skin cells in the lower levels of the epidermis. As the skin cells move toward the stratum corneum, they start expressing different proteins and making lipids and other molecules to form barrier impermeable to pathogens such as viruses and bacteria. When skin cells reach their final state, before they slough off as skin flakes, the profilaggrin is chopped up into small bits called peptides, and these filaggrin peptides bind filaments of keratin inside the cells. The filaments then get cross-linked by enzymes--something like the way fiberglass and resin combine to make one godawfully tough material.

If you have a mutation in your filaggrin gene (these mutations appear to be dominant, from what I can tell) then your skin has a crappy fiberglass coating instead of a smooth, impermeable one. It lets water out; it lets pathogens and allergens in.

This skin defect may be at the root of eczema. As a baby, if your skin is defective, it lets in viruses and allergens, which induce inflammation. And then because of the chronic inflammation, you then develop the allergies and sensitivities that later manifest as the confusing food-, aero-allergen, and stress-related flareups of classic eczema.

So why does eczema affect 20% of children, and then mostly disappear--though not for me, nor 2% of adults? What happens as kids grow up?

Fascinating stuff! You can't blame the scientists for being interested. I just wish the problem was purely academic.

Don't paint that nursery?

Ran across this today on Scientific American's website: a new study from Sweden claiming to find an association between vapors of common household chemicals (such as those found in water-based paint) and childhood incidence of allergic disease including asthma and eczema.

The research was published in an online journal called PLoS ONE. PLoS ONE, for those of you not in academia, is not in the first few tiers of scientific journals. Pretty much anyone can get their work published in PLoS ONE: you pay to get in, and the attraction is that the review process is fast. So you can't give the report that much weight. But someone thought that it was important to conduct this study. I appreciate that.

In short: For parents: if your kid's room has high levels of the chemicals propylene glycol and glycol ethers-- which are found in household cleaners and are outgassed by virtually every product of modern manufacturing--the authors claim that your kid has a 60% higher chance of developing eczema. ("Odds ratio 1.6" is how they put it.) The numbers are more convincing for asthma and allergic rhinitis.

The authors speculate that the chemicals may irritate the mucous membranes of the airways and thus induce inflammation...the connection gets a little vague.

What can you do? Before your kid is born, don't paint his or her room to make the nursery look nice. Apparently water-based paints contain these chemicals, and release them over time. So: oil-based paints then? I suspect they aren't so great either. Just don't paint.

If only Justin Bieber had eczema

If you want a blog to succeed, it's not enough just to write it--this has to be obvious to anyone who's tried. It's not enough to find a compelling topic and write thoughtful essays or even pop-eyed political rants. You have to connect to your audience and sell your blog.

I find self-promotion is about as fun as standing up in front of the class in sixth grade to give a presentation on newts. Fortunately, technology has made it slightly easier for people like me. There's Twitter, my main marketing tool until Google and Technorati finally register my existence. I tweet every post to this blog. And on Twitter, you get followers in a sort of pull-yourself-up-by-the-bootstraps method: you follow other people and hope they follow you back. To find people who might be interested in this stuff, I search for Twitterers whose posts include the word "eczema."

About 80% of these posts are from news outlets still regurgitating the cats-vs-dogs story of a couple weeks ago, or from sites claiming to have the miracle cure that will banish your eczema forever if only you dose yourself with primrose oil or cod livers or some homeopathic bullshit. There are people out there, though, who are bold enough to announce their current eczematous state to their 1,200 friends. (I should be so lucky to have 1,200 friends.) Most of these people are evidently aged 16-20, based on their tweetline: "Lord what my teacher talking about now"; "I am living in the library. Again :o/"; "Math homework can go away forever" and updates about the haircut of some guy named Justin Bieber.

And at least half of them are African-American. Possibly not the ones tweeting about Justin Bieber. This was a surprise to me. I'm Caucasian, of Swiss-German descent, and naturally, thinking it's all about me, I assumed that Swiss Germans had some monopoly on eczema. I've never seen an African-American with eczema. But then-- I rarely see anyone with eczema. Is this because we all cover up or stay home when we have flare-ups?

There's an interesting academic study recently out that describes eczema prevalence in children across the United States. (Haven't found good data on adults yet.) To quote the abstract: "Black race...significantly associated with a higher prevalence of eczema." Many other factors, too, of course. Even more interesting: prevalence was virtually identical for subjects of black or "multiple" race. Fascinating-- I had assumed that the history of eczema in my family was due to us coming from a region where people of similar heritage have been interbreeding for hundreds of years and keeping recessive genes in the population. I figured that what we needed to eradicate the disease was a few generations of vigorous outbreeding (OK, perhaps time to stop talking like a rancher). But, apparently, that wouldn't necessarily solve the problem.

Eczema, a family affair

Did I mention that eczema runs in my family? Those that I know for sure have it, or had it, are my father's father (deceased), whose scratching and ill temper were legendary; a cousin; my sister; me; and my daughter Voov.

My grandfather was a sea cook and a veteran of World War I. His life was hard and eczema didn't make it any easier. Then eczema skipped a generation, fortunately for my parents, and in the interim science and medicine made great improvements in emollients and steroids. We've had it much better than he did. But let's not have the impression the problem is solved. I believe some day we'll have complete control over the demon itch.

Our family probably shares a filaggrin mutation. Ten years from now, when you can get your genome sequenced for a hundred dollars, I bet that's what we're going to find. In future posts I'm going to explore what filaggrin does, or in our case doesn't do, for skin. And I'm going to ask the scientists studying filaggrin how they think their discoveries might lead to therapies or cures.

This blog is soon going to become, like eczema, a family affair. I've invited my sister to contribute posts. She's a resident or whatever you call someone who is undergoing the legalized hazing that the medical establishment enjoys inflicting after you graduate with an MD. She'll add medical legitimacy. She gets to pick her own moniker--hopefully not something to do with ferrets (she doesn't have kids at the moment, just pet ferrets). Until then, I'll call her Dr. Sis.

Dr. Sis lives in Newfoundland. So this blog is a California-Newfoundland axis. We can speak with authority on both endless summer and endless winter. The mind boggles to realize that the two regions share a continent and a language--though the latter is debatable, if you've ever met a real Newfie.

A moisturizer to steer clear of, for you Brits

Today, along with an avalanche of the usual news of perfidy and perversion this world produces, was a note from the BBC describing some research at the University of Bath. In short: putting some stuff called Aqueous Cream BP on the skin of even healthy subjects is a bad idea. (Original article here.)

Aqueous Cream BP must be a British thing-- never seen it here. Apparently the manufacturers' original intent was for it to be used as a kind of gentle cleanser, to be washed off, but doctors started telling people with eczema that they should leave it on and use it as a moisturizer. It contains 1% w/v sodium lauryl sulfate, a detergent, and people, especially kids, have for years been complaining about it stinging. Big surprise: you shouldn't use it.

I'm not sure I buy the researchers' data on how this cream thins the stratum corneum--the topmost layer of skin--but they seem to show that when you start stripping off healthy skin that has been treated with the cream, its rate of water loss increases faster than that of untreated healthy skin. (The researchers' advanced tool for stratum corneum stripping: Scotch no. 845 book tape (St. Paul, MN, U.S.A.)

The authors say that most likely the detergent is breaking down lipids between cells in the stratum corneum, and making the skin more permeable.

This is cheap, easy research. It also proves something everyone already knew was true. So it's not the kind of work I propose to fund.

But it does let me ramble about moisturizers. I grew up in Canada, where doctors always prescribed Glaxal Base for my eczema. Let it be known: although Glaxal Base contains not a molecule of sodium lauryl sulfate, it completely sucks as a moisturizer. The best stuff I've found is Eucerin, or one of its generic analogs that you can find in CVS or Longs (but not Walgreens--their version is terrible). Eucerin, like a good mayonnaise, combines awesome greasiness with light fluffiness. OK, I'm exaggerating: it goes on like cream cheese. There's a science to moisturizers and Beiersdorf, the makers of Eucerin, have got it right.

No surprise, Beiersdorf is a German company. The Germans, in my personal experience, are a step ahead in eczema treatment.

Eczema sufferers thank you, Dr. Anthrax

Voov and I are in a good stretch-- neither of us has any eczematous patches right now. Of course, that can change overnight. But when eczema isn't bothering you, you tend not to think about it-- you get to pretend everything's normal, and wear clothing that nobody but an eczema patient would find daring-- t-shirts, collarless "shirtly sweaters" (you know, those thin pullovers that were a fad a few years ago). Maybe go swimming.

Not to go on about this Atopic Dermatitis Research Network too much, but I had a thought. Why is this grant so big? One clue, maybe, is the story I mentioned yesterday (NYTimes version) about the 2-year-old son of a US soldier who developed eczema vaccinatum after his father was inoculated with vaccinia virus, the live smallpox vaccine.

The episode must have opened a lot of eyes to the danger this vaccine poses to eczema patients. But the NIH was aware of the problem beforehand. ADRN is the sequel to the ADVN, which was established as early as 2004 and perhaps before. Almost certainly the whole ADVN/ADRN focus on vaccines and eczema is a direct consequence of the 2001 anthrax attacks.

So, eczema sufferers, we can thank Bruce Ivins if, in a few years' time, drugs or other therapies start filtering down the pipeline to protect us against MRSA. Bioterror is big money. I don't know exactly how the NIH receives its funding, but the US civilian biodefense budget for financial year 2011 is about $6.5 billion. $32 million is peanuts. We should angle for more!

For me, although MRSA or staphylococcus in general is a continual concern, I feel that it would be a shame if a huge expenditure of research dollars removed the danger of eczema infection but left us all itching and scratching without relief. Let's not forget that.

A postscript: I asked a mathematical epidemiologist, Jamie Lloyd-Smith, an assistant professor at  UCLA, what fraction of the US population would have to be vaccinated against smallpox to shut down an epidemic. His answer, which he stresses is a back-of-the envelope calculation (I leave out the math):

"You can prevent an epidemic--or eliminate an endemic disease--by vaccinating a high enough proportion of people that Reff<1. This gives herd immunity...you'd need to vaccinate 70-83% of people to eliminate smallpox."

Since, including children, about 20% of the US population has experienced eczema in some form--and, say, there are three people in the average family, and even if you don't have eczema, you can't expose your child to viral danger-- it is clear that the government cannot vaccinate 70% of the population in the event of a smallpox attack without putting a small fraction at real risk of developing eczema vaccinatum. Given the loud objections of the anti-vaccination fringe to protecting their kids against measles and whooping cough--with vaccines for which the benefit overwhelmingly outweighs any imagined risk--you can imagine the trouble the government would run into if it tried to jab us all with smallpox vaccine.

Say no to smallpox vaccine

In March 2007 a two-year-old boy in Chicago contracted the smallpox virus from his father, a soldier who had recently been vaccinated prior to a tour of duty in Iraq. Only an all-out response from a Who's Who of U.S. infectious disease experts saved the boy, who had become a victim, it appears, because of an immune defect associated with eczema.

Why does this matter to you? Or to me? I read this article in Science (sorry about the paywall) at the time and the story just leaped off the page at me. It's scary. If you have eczema, you basically shouldn't get vaccinated for smallpox because the risk of dying is too high. And the effects aren't pretty.

(You may notice that I never post images of this stuff. That's my policy. I have eczema, and it grosses me out enough on my own body that I don't need to see it on anyone else's. I eat dinner after writing these posts.)

In the year following that nasty discovery, the NIH founded a research group called the Atopic Dermatitis and Vaccinia Network (ADVN) to look into why vaccinia virus can cause such an extreme reaction. Vaccinia is closely related to variola, the agent of smallpox, and used as the vaccine. In most people, it's benign. An ADVN group at the La Jolla Institute for Allergy and Immunology found that levels of "natural killer" cells, a class of white blood cells, are low in a strain of mice used as models for atopic dermatitis, and which develop "eczema vaccinatum," the same condition the Chicago boy nearly died from. In normal people, the theory is,  natural killer cells somehow keep the virus in check.

Science is complicated-- this is one paper, and it's a mouse model, but you can imagine that these results might point the way to studies that could find similar results in humans, and possibly therapies to boost natural killer cells to prevent deadly reactions to vaccine. (The ADVN must have published reams of papers, and right now I have no idea what their most significant findings were. Will have to find out.)

The ADVN has now morphed into the ADRN, the Atopic Dermatitis Research Network, the group that in July received $31.5 million from the NIH to conduct extensive research over five years into why patients with eczema are susceptible to deadly microbial infections. In the NIH's original request for proposals for this funding, they define four research areas; the first two are eczema vaccinatum and staph infections. The second two are vaccine reactions and infections from other organisms. The constraint was that applicants had to pick one of the first two areas, plus one to three of the remaining three. The successful consortium, led by Donald Leung at National Jewish Health in Denver, appears to have picked staph infections as their primary focus, according to their press release.

I wrote to Leung and he informed me that the group has not yet determined a protocol for its experiments, but will have done so by the end of the year. I can't wait to find out the details. It is an undertaking of huge scope-- ten academic centers involved. Staphylococcus, and MRSA, is surely a worthy enemy to vanquish. Imagine bringing up a child with eczema knowing that because of what they discovered on this project, you didn't have to worry about runaway staph infections. Life might not be all smooth sailing, but the fear factor would be a lot lower.

Initially, I called the NIH media department, asking whether they made the details of grant applications public. They do not, and the officer directed me to contact the scientists directly. "I'm an eczema sufferer myself," he told me. "I understand why you want to know."

Easy way to make yourself feel better: read WebMD

I just did something I shouldn't have-- but the result was, from my selfish perspective, good. Like probably 25,000 other people I got the National Eczema Association's email newsletter today. It says that CEO Julie Block is a guest expert on WebMD. Join the discussion, it said. I clicked on the link. Good Lord. Should you ever despair about your eczema, you can click on that link to instantly confirm that there are people out there doing far worse than you. Someone apparently has cactus infiltrating their entire body, pushing needles out their fingernails and reproductive organs. And then there's the tree man.

So one news item in the NEA newsletter is that the National Jewish Health Center in Denver won a $31.5 million grant to study MRSA infections in patients with eczema. This grant was awarded in July, but I broke the story two days ago. NEA, consider yourself scooped!

This in jest. There's a difference between being a blogger on your own schedule beholden to no-one and trying to get a respectable newsletter out on deadline. The NEA's newsletter and magazine are valuable resources for people like me.

I wrote to Diane Dunn, the NEA's communications and program manager, to introduce myself, and she decided to treat the anonymous internet weirdo with kid gloves. She wrote back suggesting there may be a way for us to work together. I sincerely hope so. There aren't many places you can go to to get news about eczema research. The mainstream media tends only to cover stories about dogs (this happens to be a general rule in science writing) or stories with an angle like people with eczema are "allergic to money" because there is some correlation of atopic dermatitis with higher income. Eczema is complex enough that there are results coming out of labs and clinics all the time that may pertain to your individual case. I hope to relay some of these stories.

I wrote to Adam Dormuth at National Jewish to ask him if he could give me details on the Atopic Dermatitis Research Network, a consortium of ten academic centers that was created specifically for the purpose of winning the grant, which was advertised by the NIH in a competition. If someone told me there was $31.5 million to be had, I'd call all my professor friends and get the band back together too. Anyway, haven't heard back from Mr./Dr. Dormuth. The man may prioritize his inbox the same way I do, which is

1) requests from people who really matter, like donors, politicians, ambassadors, and Newsweek  reporters

2) requests from people who matter, like faculty who have a paper coming out next week that the public affairs department doesn't have the bandwidth to write about

3) announcements about campus events featuring free food

4) spam

5) requests from anonymous bloggers

I've just wasted ten minutes trying to think of a witty ending for this post. And failing. In short: we'll get some answers about ADRN, whether it's from National Jewish or elsewhere.

Eczema: not a "wicked problem," but not an easy one either

Voov's a wiggler on her diaper table tonight. As usual. You have to spread on her steroid oil and then her moisturizer while at the same time she grabs for her ankles, trying to scratch her feet. A trick I have learned: give her a toy, and somehow her brain focuses on playing with the toy, or her motor neurons are too occupied flinging that plastic giraffe around, for the itch impulses to dominate. Distraction works.

I find this true myself. If I'm intent on a crossword or working on a fiddly bike repair, the itch-scratch cycle gets turned off. Back in college, math problems would do the same thing--except there were always the problems I couldn't solve for hours, and the stress of having to finish a problem set on deadline would set off an itching spree. I must have been a sight in the exam hall.

That reminds me-- another temporary off switch for eczema itch-- rock climbing. It demands utter focus and your brain has no time to waste on itch. Years ago, I was into top-roping with friends, and I remember the intensity. Maybe I should get back into it. (Besides, climbers develop serious pipes.)

The neurology of itch is a weird thing, and science hasn't figured it out yet. Eczema's a super-complex problem because it involves itch, genetics, immunology, factors such as psychological stress and heat, and substances such as sugar, caffeine, and alcohol. To find a cure for eczema will take a first-class interdisciplinary research and clinical team. A dedicated institute, or a committed and collaborative group at a large research university.

I was thinking the other day that you could call eczema a "wicked problem." I was inspired by reading a piece on the internet that used the phrase. But it turns out that the author of the piece was misusing "wicked problem." He really meant "super-complex" problem. "Wicked problem" is a term from social planning that refers to a societal problem that you can't even describe unless you already know the solution--and which depend on your values and point of view, and the solution of which can cause unforeseen, unwanted consequences.

Curing eczema-- the originators of "wicked problem"would call that a "tame problem." Whoever finds the answer is going to make a lot of people happy for good. Unfortunately, "tame" doesn't mean "easy."

Dr. Jazz and a truly massive eczema research grant

Today's a special day for me: yes, I'm officially one year older. At this stage of life, I'm satisfied with "Happy birthday, daddy" from the kid who can talk, a slobbery mauling from the one who can't, and a rendition of "Happy Birthday" from Hidden B, who doesn't sing out of tune so much as she sings each line in a different key.

My birthday present to myself? Either I am going to crack open that bottle of Aussie white wine and enjoy a few glasses, or I'm NOT going to open it, and spare myself the consequent itching. Ah, it's no contest: I'm going to open the bottle. You only live once.

I made my first inquiries today, to a doctor I work with professionally, about how to start a foundation. I'll call him Dr. Jazz, since he likes to play jazz on his stereo when he's in the office, so when you're in the conference room you feel like all you need is a highball and a cigarette. Dr. Jazz is deeply involved in translational research (that is, turning bench science into cures). His specialty is prostate cancer. He didn't have a ready answer for me-- he said that if someone suddenly handed me $100k I could, for starters, open a bank account in the name of the foundation. But to create a real foundation you need a lawyer. There has to be a lawyer out there willing to bill this pro bono. Dr. Jazz happens to know a wealthy donor who is on the boards of several patient advocacy foundations, and he's going to put me in touch with him, so I can get some advice and maybe an introduction.

Everyone knows that in the U.S., the National Institutes of Health are by far the most important source of funding for biomedical research. The NIH makes its funding numbers public, and you can look them up. Go to projectreporter.nih.gov and use the search engine. Type in "eczema" and see what comes up.

So I made an interesting discovery. About 45 grants were given in fiscal year 2010. Since some grants are portioned out over several years, and some major grants may have been given in 2008 or 2009 or whatever and still be active, this is just a snapshot, but it's very useful. Most of the grants are for amounts in the range $300k to $500k, with a handful at $2M. So $1M is clearly enough to fund two significant projects, but not a remarkable amount-- I am not out of line to plan on raising $1M.

Here's the humdinger. One of the grants is for $32M. It is by far the largest, two orders of magnitude greater than the median. Donald Leung (in the NIH database, he's listed as "David," but that's not his name) at the National Jewish Health Center in Denver, Colorado, is the principal investigator for an absolutely massive project called the Atopic Dermatitis Research Network. The ADRN brings together scientists from ten campuses for a five-year effort to understand and contain staph-related infections in people with eczema.

I'm going to find out more about the ADRN. From my perspective as a patient with eczema, and the father of one (and cousin, and brother, and grandson) staph infections are a truly nasty aspect of the condition. I've had two severe whole-body outbreaks in my life and I continually experience minor infections that I'm aware could always bust out into something that could put me in hospital. The possibility that the ADRN could produce valuable knowledge and real therapeutics is exciting.

We're working on it

Hidden B likes to read my posts after I put them up. Last night she protested that I had misrepresented the daughter-steroid situation--I implied that we were alternately over- and under-dosing the kid. We were not. So a correction is in order. Let no-one have the impression that Hidden B does not know what steroids are or how to properly apply them. She has a medical degree. The degree happens to be in veterinary medicine, not pediatrics, but we can all agree that kids are animals a lot of the time.

I also made a chemistry mistake. Fluocinolone acetonide (what Voov gets oiled with at critical points, at 0.01%) is not the same as fluocinonide (what I rub into local flares). Oddly, based on the chemical structures on Wikipedia--believe it or not, Wikipedia is the first reference for editors of a prominent scientific journal at which I worked--fluocinonide is fluocinolone acetonide plus a ketone group, essentially acetone. I need to ask a chemist why the one without the acetone group is called "acetonide." What really matters to me is that fluocinonide is a class II steroid (USA rankings). Fluocinolone acetonide, missing that ketone, is somehow only class IV. It alarms me that my doctors so casually prescribe something as powerful as fluocinonide; and what I find especially alarming is that it often doesn't do much for me. What is it doing TO me?

Today I learned of a YouTube project for gay and lesbian teens-- "It Gets Better." It was kicked off by Dan Savage and his partner. For years I read Savage's sex-advice column, and loved it. The guy is sharp, witty, and outrageous, and if you watch his video, you see that he's capable of great tenderness too. He cares. The point of the campaign is to support teens who may be conflicted about their sexuality, or being bullied at school. High school, say Savage and his partner, is just a phase to be endured, and then you leave the assholes behind and get on with your real life. It gets better.

For many kids with eczema, it gets better. (Anyone have a good reference for prevalence? Best I could find in a hurry was this.) The handouts I've seen say that many children clear up by age 5. But what about the rest of us? It doesn't get better. High school is hard for everyone, but it's even harder if you're the itchy kid with the weird rash on your hands, and it's going to be like that the rest of your life. What can we tell these kids? "Eczema: we're working on it." Maybe we'll figure something out for your grandchildren.

I was supposed to put steroids on her?

Got Voov's nails clipped tonight, without too much strife. Just had to distract her with a few books.

She had an appointment today with the dermatologist, who determined that we could scale back on the "Derma-Smoothe" liniment that we'd been using. Derma-Smoothe is 0.01% fluocinolone acetonide in a liquid base, with the consistency of grapeseed oil. Here's the joke--I thought her skin was getting better by itself, because I was just putting moisturizer on Voov on the nights I have her--and then Hidden B tells me that no, Voov is getting better because she's been slathering her all over with Derma-Smoothe on the nights she has her.

I know what fluocinolone acetonide is, because I have it at 0.05% in a thick ointment base, aka Lidex. It's the "strong" steroid I use, probably too casually, to control my flares. It truly is amazing how doctors will prescribe a therapeutic meant to be applied in a certain controlled manner, and then the patient gets home and forgets the details, or perhaps was never told exactly how to use it or how dangerous it is. With babies the parents have to communicate too. So there's this powerful steroid that 1) I don't use at all and 2) my wife puts all over Voov on alternate nights.

Maybe we've stumbled on the ideal dosage schedule.

Anyway, she's doing well now, so Derma-Smoothe is to be used only for limited stretches on flares.

I'd like to see the day there is a therapeutic or two that REALLY controls eczema and doesn't have the side effects of steroids. (I might at some point get into steroid chemistry and what they're actually doing when you use them.) Novartis, who sells pimecrolimus, and Astellas, which makes tacrolimus, would like you to think the problem is solved, but not for me it isn't. I've tried both. Pimecrolimus did bugger-all, and tacrolimus did bugger-all and gave me an otherworldly headache.

However, pimecrolimus and tacrolimus are in the general direction I would like to move eczema research. They're both immune-suppressive drugs that turn off a specific signaling pathway in T cells (that's one thing they do, at least; drugs never do just one thing). What do T cells have to do with eczema? (Gonna look into that.) What other microbial chemicals are out there in the soil? (Tacrolimus: discovered in Japanese soil bacterium.) Are there FDA-approved drugs already on the market that suppress eczema as a "side effect"? Let's get the right scientists on the job and give them the funding to get results.

Nine inch nails

Voov was in the bath tonight-- got in ahead of Shmoop, as usual, because she's not old enough to sit on the potty or brush her teeth. She plays with the bath toys and starts her most recent game-- standing up and sitting down again and again. "Oh god, she's mangling her back," says Hidden B, and it's true, she is. I had sort of noticed her rubbing her lower back, but now I see it's a red mess. "I need to cut her fingernails," says Hidden B. "You have to remind me." But cutting Voov's fingernails is a frickin' circus, and I can't face it tonight. We have to cut them right back so there's hardly a micron sticking out, and Voov fidgets and flails about, and I'm required to clown around and distract her with dancing or juggling or singing. Can't face it. Put it off until tomorrow.

My fingernails have always been an issue for me. I don't chew them. They just have to be cut back to the nail bed. Always. There's one nail in particular on my right hand, I think it's the ring finger, that seems to grow faster than the others, and I'll suddenly find myself absentmindedly gouging my arm or my leg and have to go clip my nails again. Toenails too-- the feet can develop a mind of their own and scratch each other.

I'll secretly look at other people's nails. How do women deal with these painted claws that fashion demands? And some men seem not to mind having a quarter-inch or more nail growth. Guitar players in particular give me the willies, if they grow thumbnails that double as guitar picks. Yikes. If my nails looked like that I'd be mortifying my flesh and scalp like a medieval monk.

Another couple weird things about my nails. If I look closely at them I can see these little pits, like holes on a keratin golf course. I know nail pitting is associated with psoriasis, but it's kind of freaky-- I've never personally known anyone else who had it. And almost all my fingernails have these white half-moon stripes that seem to be spaced out by maybe five days' growth. According to the same paper linked to above, that's called "leukonchyia" and doesn't signify anything. Again, freaky. Once I asked my regular doctor about it and she said confidently "That's because you have eczema in your nail bed."

As if. Some doctors act like they have all the answers. When it comes to dermatology, and eczema in particular, the medical profession is far from having the answers we need.

The sweet smell of dog

About that University of Cincinnati study. General feeling being that having a dog as a pet can only be a good thing for your baby because intense exposure to dog aeroallergen somehow has a long-term anti-inflammatory effect in those allergic to dogs, compared to cat aeroallergen, which is pure refined evil has a significant correlation with eczema at the age of 4 in kids with cat allergies.

Eczema seems to be a disease with a major autoimmune component.This kind of cohort survey research is constructive to the effort to find cures for eczema because it can highlight particular allergens and scientists can then look closely at what those allergens are doing to your immune system.

The authors mention collecting vacuum samples from the floors of people taking part in the study. They measured the concentrations of the major dog and cat allergens in dust. I was interested to find that they already know what these allergens are. These must be the active agents in skin prick tests.

It's a scientific paper so there's no mention made of this, but there should be: having a dog is a major undertaking. I know. About six years ago, Hidden B and I adopted an Australian cattle dog puppy. I loved the dog (didn't grow up with one; dad foisted a cat on us for a few years). I enjoyed going for a jog with her; going for a hike and throwing a tennis ball; trying and generally failing to teach her manners. But the work, the work. Picking up the poop in the backyard, which became a manicured latrine. Dealing with noise complaints from neighbors. Stopping the mutt from savaging the postman. And paying the kennel bill whenever we went on vacation. It was like having a kid. (In retrospect, good practice.) So you just can't expect a family with a history of atopy to casually take on caring for a dog.

But maybe someone can develop a reverse air purifier, which comes with a filter loaded with dog hair and dander, and blows a sweet, gentle doggy breeze into your house while you and your loved ones sleep.

Further into the cats-&-dogs story at the U of Cincinnati

Anyone with access to a computer has by now heard the news: "man's best friend protects against eczema in young children."

That's the short version, anyhow. I first noticed it on Twitter, and automatically retweeted, as did it seems half the Twitterverse. It's a nice short soundbite and I'm sure it played well on TV, too. (Wouldn't know--don't watch.)

This is a good introduction for me. I would like to explore the universe of eczema research, first in North America, and then beyond. I'm most familiar with the North American research sphere, having worked in it, and at the moment writing PR as part of the research-industrial complex. So I am happy to learn there is a group conducting research of this type at the University of Cincinnati. Maybe we can explore the group's work further.

There's definitely something up with cats and dogs and allergens. I know this from personal experience. I'm deathly allergic to cats. Certain species (I'm allowing for variation) in certain circumstances (like my late grandmother's apartment, which housed at least three felines of great hairiness and size, and which wasn't cleaned from approximately 1975 to 1994, when she passed away) give me instant and incredible fits of itching and sneezing. Dogs don't, although when they lick me, I get hives. I used to like cats, until I had a skin prick test that showed I had high reactivity, and ever since, they've seemed like the spawn of the devil.

So: cats and dogs. The results of the Cincinnati study are more subtle than might seem from a quick read of a mass-market website or newspaper. If you read the university's press release, or the actual paper, what the authors find is that if 4-year-old kids are allergic to dogs, their risk of developing eczema is 4 times higher than average if they did NOT have a dog in the home before they were one year old. If 4-year-olds are allergic to cats, they are 13 times more likely to have eczema than average if they DID have a cat in the home before they were one year old.

So you see the findings apply only to kids who are allergic to the pet in question. But this is interesting, because when you've become allergic to something, your immune system has had a fundamental reaction to some allergenic factor. Your B cells are producing antibodies to it. The inflammatory response is involved.

The authors are not immunologists, but they do refer to an earlier study that showed that "T cell lines of dog-allergic subjects produce high levels of interleukin-10 and interferon-gamma, cytokines associated with the induction of tolerance." The tolerance in question is to dog allergen. Not sure how being tolerant of dog allergen is related to being allergic to dogs. I'd ask the authors, but after the media blitz I don't think they'd have time for an anonymous blogger.

This paper certainly makes clear that I'm going to have to educate myself in statistics. When I'm reading about adjusting for confounding variables, I feel like I'm in one of those dreams where I forgot to wear my pants to math class.

There are other interesting factors in this paper that the media generally left out of their stories, and I'd like to discuss these in subsequent posts. Among them: genetic heritability and filaggrin mutations.

Eeyore, terrorism, and moisturizers

I said last post that I was going to announce the lucky winner(s) of the second Mark Twain Steel Trap Award.

(From Twain's autobiography, to be released this November by UC Berkeley Press; the quote refers to a man who borrowed and lost a large amount of Twain's money: "if I had his nuts in a steel trap, I would shut out all human succor and watch that trap until he died.")

Well, here's the thing. I've been reading a few of my earlier posts, and I'm not sure the tone is what I want to aim for. The aim of this blog is to raise at least $1 million for eczema research, whether that means creating a foundation or funneling major contributions to a worthy, effective organization that already exists. I want to inspire philanthropists to invest in research that leads to a cure (or cures; eczema's a many-headed beast). Would you invest with a pessimist or an optimist?

An optimist. The pessimist doesn't want to reach higher. He's enjoying it too much feeling sorry for himself and taking it out on others.

To quote A. A. Milne:

"I'm not asking anybody," said Eeyore. "I'm just telling everybody. We can look for the North Pole, or we can play 'Here we go gathering Nuts in May' with the end part of an ants' nest. It's all the same to me."

If Eeyore had eczema--which could well be the explanation for his poor attitude--he'd not be the one you'd give $1 million to in the expectation he'd find a cure.

I'm nearly done with being Eeyore. Indulge me this once. The second Mark Twain Steel Trap Award goes to the terrorists who, in 2006, plotted to bring liquid explosives on airliners flying from the UK to North America. The British police, bless 'em, foiled these men and put them in irons. But since that day--at least in North America, which is what my experience has been limited to in the last four years--you can't bring any sizeable quantity of moisturizer in your carry-on. And anything in your checked bag comes under suspicion. (Myself, I like to travel without checked baggage if I can, especially since United started charging for bags.)

The inconvenience is non-lethal, I grant you, but several times I've had to chuck out large tubs of Eucerin at security checkpoints. Eucerin is the only moisturizer I've found to do the job, and it's not cheap--depending where you get it, anything from $13 to $17 a pop. And you can't necessarily get it at your destination. So there you are stuck on an airplane getting stressed and dehydrated, and at the far end the first thing on your mind is where the nearest pharmacy is. When you find one, it may be open, or not, and may or may not carry Eucerin, at a reasonable or exorbitant price.

Messrs. Ali, Sarwar, Hussain, Savant, Khan, Zaman, and any I may have omitted: your prize, sirs.

(No succor for you.)

I'm done awarding prizes for now, but can't rule it out absolutely in the future, should I come across a deserving honoree.

The silver lining from one of these Eucerin-chucking incidents was that I ended up in San Francisco (having flown from DC where I was living at the time) on a Sunday, when all Walgreens pharmacies are inexplicably closed, and was forced to pick some random moisturizer from an aisle in Safeway. It turned out to be a winner. Aveeno Daily Moisturizing Lotion with dimethicone is pretty good stuff, even if it's not in the same league as Eucerin. The dimethicone is a rubbery sealant that leaves you with a pleasant plasticky feeling. If you're into that kind of thing.