Researchers in London have developed a mathematical model of a molecular feedback loop thought to cause persistent inflammation in eczema patients.
Normal skin is maintained in a steady state in which old skin cells slough off and are continually replaced by new ones pushing from beneath. Flattened skin cells called keratinocytes are initially held together with bonds that are digested by enzymes called "kallikreins," according to a recent paper in the journal PLoS One. Kallikreins also cleave a receptor called PAR2 that, in normal skin, controls the skin steady state but, in eczematous skin, turns on a type of autoimmune response.
The authors of the PLoS One paper observe that, in eczema, inflammation that can start with a mild or short-lived stimulus (such as scratchy clothing) persists far longer than it does in healthy skin. They make the hypothesis that this is the result of a feedback loop between PAR2 and kallikreins. Even when the initial stimulus is gone, this feedback loop--like a screaming speaker connected to a microphone in front of it--keeps eczematous skin inflamed.
The authors ran their model on a computer (actually, they probably ran many models thousands of times on different computers, and tweaked tens or hundreds of parameters until they got the answers they wanted) and showed that it behaved consistently with data from real patients. So it's consistent with reality that there may be a positive feedback between PAR2 and kallikreins, or a negative feedback between PAR2 and a molecule called LEKTI that inhibits kallikreins.
They don't say this right out, but a potential benefit of this work--way, way, way down the line--is that if further modelling and experiments show that this feedback loop is real, then we may be able to break the loop with a custom-designed or -discovered drug, and stop inflammation quickly in eczema.
Saturday, May 28, 2011
Tuesday, May 24, 2011
NEA eczema research grants too small. Philanthropist needs to step up
Julie Block at the National Eczema Association recently announced that the NEA offers research grants of $10-25k/year. I am all for supporting eczema research, both basic investigations into the causes of eczema and applied projects to help treat it. That’s why, as a patient and parent, although I applaud the NEA’s program--who else is doing this for us?--but I think it’s way too small. Someone needs to give it a boost.
Now, I know that the NEA’s primary purpose is patient support, and I know that sometimes these tiny grants can be used as leverage on bigger grant applications. Martin Steinhoff, I think, told me that NIH “study groups” that decide who gets federal money give great weight to grants from patient advocacy groups like NEA. They're a seal of approval.
Nevertheless, let me give a bit of perspective. Modern biology is expensive. The salary alone of a single graduate student is $50k/yr (counting overhead). The last time I looked at NIH research grants, the median grant was $250k. And, from what I’ve seen, the budget for a single lab at the University of California is at least $1M/year. Bigger labs, $2.5M/yr, a hundred times as much as an NEA grant.
Plus, here’s another issue: I don’t think leading scientists are going to bother applying for $10-25k grants. They’re not worth the time of a Kevan Shokat or a Carolyn Bertozzi: an innovator who could make radical discoveries that would transform a research field.
So we need to think bigger. How can the NEA get more money for its grant programs? We can’t rely on the NIH alone to fund eczema research. They don’t even include eczema as a condition worth listing in their public accounts.
The NEA is not going to get money from the government. And at their current annual subscription fee, they’re not going to get it from you or me. They might get it from one or more wealthy philanthropists who either themselves suffer from eczema or who have close family members who do.
And these philanthropists are going to want to know that they are not throwing their money away, giving it to scientists to buy expensive toys. They are going to want to know there is good management in place, with a plan that includes milestones. Would we be ready to convince such a philanthropist that we merit their money?
Or, possibly, someone would be interested in offering a prize, like an X Prize (an Ecz Prize?) of a million dollars or more for the first research group to, say, provide an effective pH-balanced filaggrin-based scalp moisturizer. Big prizes, so the scuttlebutt goes, offer a factor of ten leverage. You pay a prize of $1 million, but you get $10 million worth of research done by competing groups. Plus, a prize draws attention to a challenge.
The question is: what goal would a prize be offered for? Eczema is such a complex problem, and we’re far from a complete understanding of it. So what realistic, inspirational goals could a prize committee set? I’d be happy to learn of parallels where this approach has worked for other conditions.
Now, I know that the NEA’s primary purpose is patient support, and I know that sometimes these tiny grants can be used as leverage on bigger grant applications. Martin Steinhoff, I think, told me that NIH “study groups” that decide who gets federal money give great weight to grants from patient advocacy groups like NEA. They're a seal of approval.
Nevertheless, let me give a bit of perspective. Modern biology is expensive. The salary alone of a single graduate student is $50k/yr (counting overhead). The last time I looked at NIH research grants, the median grant was $250k. And, from what I’ve seen, the budget for a single lab at the University of California is at least $1M/year. Bigger labs, $2.5M/yr, a hundred times as much as an NEA grant.
Plus, here’s another issue: I don’t think leading scientists are going to bother applying for $10-25k grants. They’re not worth the time of a Kevan Shokat or a Carolyn Bertozzi: an innovator who could make radical discoveries that would transform a research field.
So we need to think bigger. How can the NEA get more money for its grant programs? We can’t rely on the NIH alone to fund eczema research. They don’t even include eczema as a condition worth listing in their public accounts.
The NEA is not going to get money from the government. And at their current annual subscription fee, they’re not going to get it from you or me. They might get it from one or more wealthy philanthropists who either themselves suffer from eczema or who have close family members who do.
And these philanthropists are going to want to know that they are not throwing their money away, giving it to scientists to buy expensive toys. They are going to want to know there is good management in place, with a plan that includes milestones. Would we be ready to convince such a philanthropist that we merit their money?
Or, possibly, someone would be interested in offering a prize, like an X Prize (an Ecz Prize?) of a million dollars or more for the first research group to, say, provide an effective pH-balanced filaggrin-based scalp moisturizer. Big prizes, so the scuttlebutt goes, offer a factor of ten leverage. You pay a prize of $1 million, but you get $10 million worth of research done by competing groups. Plus, a prize draws attention to a challenge.
The question is: what goal would a prize be offered for? Eczema is such a complex problem, and we’re far from a complete understanding of it. So what realistic, inspirational goals could a prize committee set? I’d be happy to learn of parallels where this approach has worked for other conditions.
Friday, May 20, 2011
Managing eczema on your scalp
Scalp eczema doesn’t get much press, but a lot of us live with the problem every day. Me, for example: I own virtually no dark-colored tops, because a snow of skin flakes shows up within seconds. I comb my hair, or what’s left of it (hey, I’m a 40-year-old man) not to straighten tangles, but to clear up any rogue scabs. And I’ve had to develop my own regimen for scalp care because nobody ever handed me a pamphlet.
Eczema on your scalp is the same as it is everywhere else, except for two complications.
I keep my hair very short. I use a #2 buzzer on my head. I can get away with this because I’m a man in a job where hairstyle doesn’t matter. The #2 keeps my hair short enough that I can apply steroid creams or ointments but long enough that other people can’t see my sores or scabs easily.
Steroid ointments (say, fluocinonide 0.05%, my “strong” option) come with warnings about folliculitis. You’d think this would be a problem on the scalp, but I haven’t found it to be. I try to use it sparingly, though.
Many shampoos and conditioners brag about their moisturizing properties, but they refer to what they do for your hair, not your scalp. In my experience, both shampoos and conditioners have detergents that dry out my scalp to a painful degree, and fragrances that irritate it. What to do?
Go fragrance-free, for a start. Or as fragrance-free as you can; medicated shampoos seem all to come with masking fragrances to hide their smell. Options that I’m aware of are coal tar (say, T-Gel, Zetar, Polytar); zinc pyrithione (e.g. Head and Shoulders, Selsun Blue); and iodine (Betadine). I spent several years in the UK where Betadine is available as a shampoo. I haven’t seen it as a shampoo in North America, but Hidden B, who’s a veterinarian, has a bottle of it that she uses on dogs.
Let’s tackle these one at a time, and ignore any qualms about weird smells.
Zinc pyrithione (http://en.wikipedia.org/wiki/Zinc_pyrithione) is an antimicrobial that kills bacteria and fungi. It doesn’t work for me. This is probably because my primary problem is in the skin barrier, not a secondary infection. I may also have infections that it does or doesn’t clear up.
I remember Betadine being relatively pleasant, and leaving terrible brown stains on everything. I think it worked well because it didn’t have a very strong detergent component, and was much more a medical than a cosmetic product. I’m all in favor of this. Hey, maybe I should borrow some from Hidden B. Again, the active ingredient in Betadine is iodine, because it’s a broad-spectrum antimicrobial.
Coal tar works for me, but only in the strongest formulation. I use T-Gel Extra Strength and Polytar. In the past these have been difficult to find where I live in California, and I have bought them online from a Canadian source, but recently I’ve seen tar shampoos on the shelf in pharmacies here.
Coal tar’s a bit of an oddity. It is not a pure substance that can be easily quantified. It is a mixture of apparently up to 20,000 organic compounds, and it’s a traditional treatment for scaling skin diseases that reduces inflammation and itch and kills microbes. Which of the 20,000 compounds are doing what is anyone’s guess, and there have occasionally been claims that coal tar causes cancer. I don’t take these seriously because there has never been a conclusive study and if there were a large risk we’d know about it by now. (See a recent study here.) I think that it matters very much which brand of coal tar you use, because different brands are probably from different sources and contain different stuff.
What I DO take seriously is the increased sensitivity to UV that comes with using tar shampoo. The days I use it, I often find I get lightly sunburned on my face. Sunburn = cancer risk. So if I were going to spend a day outside, I’d be careful not to use tar shampoo that morning.
The more I learn about eczema, though, the more I understand that we might not want to use a strong antiseptic on our head too much. We probably have a flora of beneficial bacteria and fungi living on our scalps, and we ought to keep them healthy while killing off the S. aureus etc. that cause us so much grief.
Lastly, for moisturizing: every morning, and after I shower (which I do not do every day), I rub jojoba oil into my scalp. Jojoba’s a very light oil, and it doesn’t make my head too greasy. I think grapeseed or walnut oil would also do the job, but olive oil would be too heavy. Sometimes, when I have really dry skin, I have resorted to rubbing Eucerin into my scalp, but this is a bit gross.
What are your solutions to cooling itch and moisturizing on your scalp? I’d be interested to hear them.
Eczema on your scalp is the same as it is everywhere else, except for two complications.
- most people have hair on their heads, which makes it difficult and unsightly to apply thick creams and ointments
- it’s right out in the open where everyone can see. You can hide it only with long hair, and long hair makes it difficult to treat the scalp.
I keep my hair very short. I use a #2 buzzer on my head. I can get away with this because I’m a man in a job where hairstyle doesn’t matter. The #2 keeps my hair short enough that I can apply steroid creams or ointments but long enough that other people can’t see my sores or scabs easily.
Steroid ointments (say, fluocinonide 0.05%, my “strong” option) come with warnings about folliculitis. You’d think this would be a problem on the scalp, but I haven’t found it to be. I try to use it sparingly, though.
Many shampoos and conditioners brag about their moisturizing properties, but they refer to what they do for your hair, not your scalp. In my experience, both shampoos and conditioners have detergents that dry out my scalp to a painful degree, and fragrances that irritate it. What to do?
Go fragrance-free, for a start. Or as fragrance-free as you can; medicated shampoos seem all to come with masking fragrances to hide their smell. Options that I’m aware of are coal tar (say, T-Gel, Zetar, Polytar); zinc pyrithione (e.g. Head and Shoulders, Selsun Blue); and iodine (Betadine). I spent several years in the UK where Betadine is available as a shampoo. I haven’t seen it as a shampoo in North America, but Hidden B, who’s a veterinarian, has a bottle of it that she uses on dogs.
Let’s tackle these one at a time, and ignore any qualms about weird smells.
Zinc pyrithione (http://en.wikipedia.org/wiki/Zinc_pyrithione) is an antimicrobial that kills bacteria and fungi. It doesn’t work for me. This is probably because my primary problem is in the skin barrier, not a secondary infection. I may also have infections that it does or doesn’t clear up.
I remember Betadine being relatively pleasant, and leaving terrible brown stains on everything. I think it worked well because it didn’t have a very strong detergent component, and was much more a medical than a cosmetic product. I’m all in favor of this. Hey, maybe I should borrow some from Hidden B. Again, the active ingredient in Betadine is iodine, because it’s a broad-spectrum antimicrobial.
Coal tar works for me, but only in the strongest formulation. I use T-Gel Extra Strength and Polytar. In the past these have been difficult to find where I live in California, and I have bought them online from a Canadian source, but recently I’ve seen tar shampoos on the shelf in pharmacies here.
Coal tar’s a bit of an oddity. It is not a pure substance that can be easily quantified. It is a mixture of apparently up to 20,000 organic compounds, and it’s a traditional treatment for scaling skin diseases that reduces inflammation and itch and kills microbes. Which of the 20,000 compounds are doing what is anyone’s guess, and there have occasionally been claims that coal tar causes cancer. I don’t take these seriously because there has never been a conclusive study and if there were a large risk we’d know about it by now. (See a recent study here.) I think that it matters very much which brand of coal tar you use, because different brands are probably from different sources and contain different stuff.
What I DO take seriously is the increased sensitivity to UV that comes with using tar shampoo. The days I use it, I often find I get lightly sunburned on my face. Sunburn = cancer risk. So if I were going to spend a day outside, I’d be careful not to use tar shampoo that morning.
The more I learn about eczema, though, the more I understand that we might not want to use a strong antiseptic on our head too much. We probably have a flora of beneficial bacteria and fungi living on our scalps, and we ought to keep them healthy while killing off the S. aureus etc. that cause us so much grief.
Lastly, for moisturizing: every morning, and after I shower (which I do not do every day), I rub jojoba oil into my scalp. Jojoba’s a very light oil, and it doesn’t make my head too greasy. I think grapeseed or walnut oil would also do the job, but olive oil would be too heavy. Sometimes, when I have really dry skin, I have resorted to rubbing Eucerin into my scalp, but this is a bit gross.
What are your solutions to cooling itch and moisturizing on your scalp? I’d be interested to hear them.
Monday, May 9, 2011
Gil Yosipovitch on alternative therapies for itch
The basic problem with treating chronic itch is that there is no cure for most conditions, including eczema. But several approaches reduce the severity by a significant amount. Some of these approaches are “Western” medicine, which I take to mean they are based on refined drugs manufactured by a pharma company. Some are “alternative,” which includes acupuncture, probiotics, “Chinese medicine” (that is, herbs that probably contain active ingredients that have not been isolated and refined into “Western” drugs), and others. Gil Yosipovitch, a world expert on itch, combines both in his approach, without overt prejudice--as long as the alternative component is not patently ridiculous.
Psychology plays a large part in Y’s method. “There are a lot of issues involved in the suffering that are beyond dermatology,” he says. “We use a lot of meds that come from psychology.”
He works with an acupuncturist. He collaborates with a practitioner of healing touch.
Here’s an aside: my own mother practices healing touch, and in past years I have mocked her for it, because there is no way that waving your hands over someone’s body is going to cause physiological changes through the medium of some imaginary “energy field” that has no connection with the laws of physics. But here’s the rub: if the patient believes there is such a connection, then I acknowledge that it is possible that undergoing healing touch could relax the patient and, via psychological paths, relieve itch or pain. Won’t work for me, though; I don’t believe in it!
“I’m a physician--I’m OK with the placebo effect,” Y says. Y doesn’t care, as long as the patient feels better. He found out that his acupuncturist has expertise in itch, and his patients who undergo acupuncture see their symptoms relieved by 20-30%. That’s better than he sees with most drugs. “Why should I prescribe drugs with side effects?” he asks. “We don’t know everything.” One of his patients was taking “enough meds for an elephant,” but they didn’t do much, and it was healing touch that appeared to improve his condition.
This holds, he says, only for chronic itch. Acute itch, that is caused by something like poison ivy or insect bite, likely has a well-defined treatment. And in any case, why worry about acute itch? It will go away. (That’s my opinion, not his.)
Probiotics: he’s not super-keen on them, but he sees a lot of people asking about them. “We have to address the issue,” he says. Again, if it works, it works, so why not try eating yogurt if it seems like a good idea.
But sometimes he sees ads for less legitimate treatments such as garlic pills or suppositories. “That’s not what I want my patients to try,” he says.
I’m confused. It seems hard to draw any sort of boundary between valid and invalid therapies, if you’re OK with healing touch. Perhaps with healing touch, or yoga, if you are “treated” or practice it regularly, there is a rhythmic relaxation effect, whereas garlic pills or their ilk are unlikely to produce anything but a weak, transitory placebo effect. However, Y knows what he sees, and he sees that healing touch has a practical, beneficial outcome.
Also, it could be that genuine caring human contact reduces anxiety. A theory occurs to me: maybe the apparent increase in incidence of eczema in developed countries is partly related to social alienation in modern life. We spend so much time dealing with machines instead of people, and so much time with strangers instead of friends and family. Can we improve our eczema symptoms by spending more time with family?
I doubt it, unfortunately. Ask any mother of a young child with eczema. It’s not that the mother doesn’t care, or isn’t doing her best to try to calm her child.
In this blog I intend mostly to pursue Western therapy as a means of treating eczema or relieving itch. I’m open-minded, though, and I hope not to bad-mouth any therapies without good reason. So, within reason, I’ll try anything myself and see if it works. That includes vitamin D. In the near future I will try a course of 4000 IU vitamin D per day, and we’ll see what happens.
With itch medicine, Y says, “large studies are a problem” because itch has so many potential causes and pathways that it’s hard to find a large identical test population. “You can’t give just one antibody for itch. That’s a simplistic approach.” And so personalized medicine, a customized approach for each of us, is our future. The responsibility lies with us. But we already knew that.
Psychology plays a large part in Y’s method. “There are a lot of issues involved in the suffering that are beyond dermatology,” he says. “We use a lot of meds that come from psychology.”
He works with an acupuncturist. He collaborates with a practitioner of healing touch.
Here’s an aside: my own mother practices healing touch, and in past years I have mocked her for it, because there is no way that waving your hands over someone’s body is going to cause physiological changes through the medium of some imaginary “energy field” that has no connection with the laws of physics. But here’s the rub: if the patient believes there is such a connection, then I acknowledge that it is possible that undergoing healing touch could relax the patient and, via psychological paths, relieve itch or pain. Won’t work for me, though; I don’t believe in it!
“I’m a physician--I’m OK with the placebo effect,” Y says. Y doesn’t care, as long as the patient feels better. He found out that his acupuncturist has expertise in itch, and his patients who undergo acupuncture see their symptoms relieved by 20-30%. That’s better than he sees with most drugs. “Why should I prescribe drugs with side effects?” he asks. “We don’t know everything.” One of his patients was taking “enough meds for an elephant,” but they didn’t do much, and it was healing touch that appeared to improve his condition.
This holds, he says, only for chronic itch. Acute itch, that is caused by something like poison ivy or insect bite, likely has a well-defined treatment. And in any case, why worry about acute itch? It will go away. (That’s my opinion, not his.)
Probiotics: he’s not super-keen on them, but he sees a lot of people asking about them. “We have to address the issue,” he says. Again, if it works, it works, so why not try eating yogurt if it seems like a good idea.
But sometimes he sees ads for less legitimate treatments such as garlic pills or suppositories. “That’s not what I want my patients to try,” he says.
I’m confused. It seems hard to draw any sort of boundary between valid and invalid therapies, if you’re OK with healing touch. Perhaps with healing touch, or yoga, if you are “treated” or practice it regularly, there is a rhythmic relaxation effect, whereas garlic pills or their ilk are unlikely to produce anything but a weak, transitory placebo effect. However, Y knows what he sees, and he sees that healing touch has a practical, beneficial outcome.
Also, it could be that genuine caring human contact reduces anxiety. A theory occurs to me: maybe the apparent increase in incidence of eczema in developed countries is partly related to social alienation in modern life. We spend so much time dealing with machines instead of people, and so much time with strangers instead of friends and family. Can we improve our eczema symptoms by spending more time with family?
I doubt it, unfortunately. Ask any mother of a young child with eczema. It’s not that the mother doesn’t care, or isn’t doing her best to try to calm her child.
In this blog I intend mostly to pursue Western therapy as a means of treating eczema or relieving itch. I’m open-minded, though, and I hope not to bad-mouth any therapies without good reason. So, within reason, I’ll try anything myself and see if it works. That includes vitamin D. In the near future I will try a course of 4000 IU vitamin D per day, and we’ll see what happens.
With itch medicine, Y says, “large studies are a problem” because itch has so many potential causes and pathways that it’s hard to find a large identical test population. “You can’t give just one antibody for itch. That’s a simplistic approach.” And so personalized medicine, a customized approach for each of us, is our future. The responsibility lies with us. But we already knew that.
Friday, May 6, 2011
Thinking about a comeback
Hey all.
I have been thinking about returning to this blog--I miss keeping up with the latest research, and sharing ideas with people.
But as you might have read below, I am struggling with some neck and back trouble probably caused by computer use or poor ergonomics. My job involves sitting in front of a computer, and it doesn't feel good toward the end of the day, and I sure don't feel like aggravating it with more computer time after I get home and help feed the kids and put them to bed and do my prescribed physiotherapy. Plus I don't have much spare time anyway.
So bear with me--maybe I can write shorter posts during the odd lunch time; maybe I can do some video posts.
At least I feel like I owe you the second half of my interview with Gil Yosipovitch.
One new thing for now: did anyone notice this link, part of the NIH's campaign for public accountability? It's a list of all the NIH's research expenditures--I think their annual budget is $20 billion, but I haven't taken the time to add up the totals. The list shows money spent per disease, and there are a lot of diseases in the list. But there's one that seems to be missing: eczema. Is it really not there? Not under atopic dermatitis or some other name? Apparently not. Maybe it comes under psoriasis? Does anybody know?
Surely they can't not be funding eczema research. (I KNOW they are at least funding Donald Leung's multisite project.)
I have been thinking about returning to this blog--I miss keeping up with the latest research, and sharing ideas with people.
But as you might have read below, I am struggling with some neck and back trouble probably caused by computer use or poor ergonomics. My job involves sitting in front of a computer, and it doesn't feel good toward the end of the day, and I sure don't feel like aggravating it with more computer time after I get home and help feed the kids and put them to bed and do my prescribed physiotherapy. Plus I don't have much spare time anyway.
So bear with me--maybe I can write shorter posts during the odd lunch time; maybe I can do some video posts.
At least I feel like I owe you the second half of my interview with Gil Yosipovitch.
One new thing for now: did anyone notice this link, part of the NIH's campaign for public accountability? It's a list of all the NIH's research expenditures--I think their annual budget is $20 billion, but I haven't taken the time to add up the totals. The list shows money spent per disease, and there are a lot of diseases in the list. But there's one that seems to be missing: eczema. Is it really not there? Not under atopic dermatitis or some other name? Apparently not. Maybe it comes under psoriasis? Does anybody know?
Surely they can't not be funding eczema research. (I KNOW they are at least funding Donald Leung's multisite project.)
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