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.)