Well, the time has come. I'm retiring from writing this blog.
It's a question of time. I don't have any. I work at a university, and in the start of fall term is hectic. Everyone wants to schedule their events from September to December. Courses are starting up. Important people are visiting.
And at the same time, I'm the father of two kids who are starting their own school years. There are the usual tensions with new teachers and fellow students, there's the endless making of school lunches, the PTA and Dad's Club meetings. Something I've realized: the power you have as a parent of a public-school kid depends on how much time you're putting into raising money for the school. If I find any free time, I need to be ready to put it into my kids and their school.
The lack of good subject matter is another issue. To write a blog you have to find a niche. My niche has been eczema research. It turns out that when you have a narrow niche it's often hard to find anything worth writing about. There appears to be a lot of research coming out, but in reality it is very rare to see anything that you could genuinely get excited about. Most research is published "salami-style," where the scientists report some tiny new finding that adds ever so slightly to the enormous pile of existing work. The ratio of valuable information to filler is very small. Sorting through the internet's fire hose takes time I don't have.
True, the academic term will eventually end, but I won't be returning. I don't want to blog in fits and starts.
You might, however see me writing occasionally on the National Eczema Association website.
I have enjoyed blogging. I've met some great people online and in person. I've learned loads about the medical condition I and my family live with. Not much has improved, but I feel like I now understand better what makes my skin the way it is.
For several months, I have been waiting for a cool new project to come out, one that I've been involved with in a small way. When it does appear, I'll add a post about it so it gets some publicity from being on top. You will like this new thing, I think.
Thanks for reading. Good luck keeping your skin healthy.
Tuesday, September 3, 2013
Thursday, August 1, 2013
Eczema, food allergies, and summer travel
Midsummer it's hard to find time to post. We're taking two weeklong family vacations not so far apart and with planning and packing and then getting swamped with work when you get back there's not much time to write.
Two aspects of traveling are relevant to this blog: how to take your eczema pharmacy along with you, and how to handle your kid's food allergies.
Last Saturday we got back from a trip to a family camp in the Sierra Nevada. It was awesome. I didn't think about work for a whole week and was so stress-free that I could jump in the pool whenever I felt like it and strut around in just my bathing suit. You've got to enjoy these times when you have them.
We ate in the camp mess hall. The staff were great about telling us what the ingredients were in all the food. Often they could give us a special dish without nuts or dairy, which are the two things my daughter's allergic to. But of course, she's a picky eater, and you can never tell what she's going to go for.
When we got back, I read about a tragic incident at a summer camp near Sacramento where a 13-year-old girl died after one bite of a Rice Krispies square containing peanuts. My daughter doesn't have an anaphylactic reaction to anything--not yet--but this was a sober reminder of how deadly nut allergies can be.
Our next trip starts on Wednesday when we fly to Nova Scotia for my parents' 50th wedding anniversary. We often go to NS in August and last year, coming back, we spent an extra day in Newark airport thanks to United Airlines, which we are NEVER FLYING AGAIN. I had run out of any moisturizer or steroid, which was my fault--but try finding fragrance-free moisturizer in the airport shops. Not going to happen. By the time we got home, my eczema was out of control and took several days to cool down to a point where I could appear in public.
Also, being out of food and having a kid with allergies in an airport was a different kind of nightmare. You can't find an ingredient list anywhere and everything seems to have nuts or dairy or whatever. My daughter was essentially reduced to eating potato chips for the better part of 24 hours, but we did gamble on getting her noodles from a random Asian restaurant. Just glad, now that I know she's allergic to sesame, that Asian restaurants in airports are far from authentic.
So this year? I'm going to bring too much moisturizer. And we're going to pack a day's worth of safe food for my daughter.
Hopefully we won't need it--we're flying Air Canada.
Two aspects of traveling are relevant to this blog: how to take your eczema pharmacy along with you, and how to handle your kid's food allergies.
Last Saturday we got back from a trip to a family camp in the Sierra Nevada. It was awesome. I didn't think about work for a whole week and was so stress-free that I could jump in the pool whenever I felt like it and strut around in just my bathing suit. You've got to enjoy these times when you have them.
We ate in the camp mess hall. The staff were great about telling us what the ingredients were in all the food. Often they could give us a special dish without nuts or dairy, which are the two things my daughter's allergic to. But of course, she's a picky eater, and you can never tell what she's going to go for.
When we got back, I read about a tragic incident at a summer camp near Sacramento where a 13-year-old girl died after one bite of a Rice Krispies square containing peanuts. My daughter doesn't have an anaphylactic reaction to anything--not yet--but this was a sober reminder of how deadly nut allergies can be.
Our next trip starts on Wednesday when we fly to Nova Scotia for my parents' 50th wedding anniversary. We often go to NS in August and last year, coming back, we spent an extra day in Newark airport thanks to United Airlines, which we are NEVER FLYING AGAIN. I had run out of any moisturizer or steroid, which was my fault--but try finding fragrance-free moisturizer in the airport shops. Not going to happen. By the time we got home, my eczema was out of control and took several days to cool down to a point where I could appear in public.
Also, being out of food and having a kid with allergies in an airport was a different kind of nightmare. You can't find an ingredient list anywhere and everything seems to have nuts or dairy or whatever. My daughter was essentially reduced to eating potato chips for the better part of 24 hours, but we did gamble on getting her noodles from a random Asian restaurant. Just glad, now that I know she's allergic to sesame, that Asian restaurants in airports are far from authentic.
So this year? I'm going to bring too much moisturizer. And we're going to pack a day's worth of safe food for my daughter.
Hopefully we won't need it--we're flying Air Canada.
Thursday, July 18, 2013
Eczema patients not protected by intradermal flu vaccine
When I talked to Donald Leung earlier this week (he's head of pediatric allergy & immunology at National Jewish Health, and leads the Atopic Dermatitis Research Network) he mentioned one interesting result that has already emerged from a small-scale ADRN trial. Leung and others showed that patients with atopic dermatitis were not adequately protected, by FDA standards, by the new influenza vaccine Fluzone.
Fluzone is administered using a super-short needle--the technique is called "intradermal" injection in which the vaccine gets squirted into the upper skin layers rather than muscle tissue.
Presumably the super-short needle is less scary than a regular needle, and more people will get their flu vaccinations this way; it could be a public health issue in the event of a flu pandemic.
Scientists know that the immune system functions differently in the skin of patients with eczema. Leung and colleagues looked at how 20 eczema patients fared with Fluzone, compared to 20 non-atopic patients. Twenty-eight days after vaccination, they measured the levels of flu antibodies in the patients' blood. The non-atopic patients met the FDA standard; the eczema patients did not.
The scientists published their results in a preliminary form as an abstract at the meeting earlier this year of the American Academy of Allergy, Asthma and Immunology.
Fluzone is administered using a super-short needle--the technique is called "intradermal" injection in which the vaccine gets squirted into the upper skin layers rather than muscle tissue.
Presumably the super-short needle is less scary than a regular needle, and more people will get their flu vaccinations this way; it could be a public health issue in the event of a flu pandemic.
Scientists know that the immune system functions differently in the skin of patients with eczema. Leung and colleagues looked at how 20 eczema patients fared with Fluzone, compared to 20 non-atopic patients. Twenty-eight days after vaccination, they measured the levels of flu antibodies in the patients' blood. The non-atopic patients met the FDA standard; the eczema patients did not.
The scientists published their results in a preliminary form as an abstract at the meeting earlier this year of the American Academy of Allergy, Asthma and Immunology.
Wednesday, July 17, 2013
New NEA post: Atopic Dermatitis Research Network needs trial participants
This week you'll find me blogging over at the National Eczema Association website. I interviewed Donald Leung of National Jewish Health about the Atopic Dermatitis Research Network. Three years in to a $42M program to investigate the links between genetics and our susceptibility to skin infections, the ADRN is registering patients with the NIH before proceeding with clinical trials.
They still need black and Hispanic patients to sign up--eczema, genetics, and skin pathogens are different for different ethnic groups. The better your demographic is represented in the trials, the more that scientists will learn that applies to you.
The ADRN has centers in Boston, Chicago, Denver, Los Angeles, Portland OR, and Rochester NY.
If you're interested in participating, email Judy Lairsmith at National Jewish or call 1-888-413-5852.
They still need black and Hispanic patients to sign up--eczema, genetics, and skin pathogens are different for different ethnic groups. The better your demographic is represented in the trials, the more that scientists will learn that applies to you.
The ADRN has centers in Boston, Chicago, Denver, Los Angeles, Portland OR, and Rochester NY.
If you're interested in participating, email Judy Lairsmith at National Jewish or call 1-888-413-5852.
Wednesday, July 10, 2013
Irwin McLean's filaggrin readthrough drug could be revolutionary
Recently I predicted that nothing resembling a cure for eczema would appear for at least 25 years. I followed that up with a prediction that if a surprise cure were to emerge, it would be an anti-itch therapy.
At least one reader disagreed, and pointed me to a strategy now being developed at the University of Dundee in Scotland: drugs to stimulate or enable filaggrin expression in patients with one or two defective copies of the corresponding gene, FLG. At least one such drug is in the very earliest stages of drug development, toxicology studies in animals. If the drug succeeds in human clinical trials, we might see it in clinics in about 15 years. Potentially, such a drug could help some of the patients most severely affected by eczema.
The best review on filaggrin I’ve seen was co-written by three authors, two of whose names I am familiar with as among the biggest in the field of eczema research: Irwin McLean, who led the team that linked mutations in FLG to increased risk of developing ichthyosis vulgaris and eczema, and Donald Leung, principal investigator of the Atopic Dermatitis Research Network. (The first author is Alan Irvine, a colleague of McLean’s who works in Ireland.)
FLG is a giant, and unusual, gene, one of the last to be sequenced by the Human Genome Project. It encodes an enormous protein, profilaggrin, which contains from 10 to 12 repeats that are cleaved off into individual filaggrin units. Filaggrin itself has several important roles in the upper layers of the skin: it flattens skin cells into their characteristic final shape; it helps bind these cells together into a barrier; and it breaks down into the acidic “natural moisturizing factor.”
Many mutations have been found in FLG. Interestingly, if you take any particular ethnic group (say Japanese), there will be a characteristic profile of mutations for this group that is likely to be different than the profile for another group (say Scottish).
All filaggrin variants are either “nonsense” or “frameshift” mutations in DNA that encodes protein (as opposed to so-called “junk DNA”). In a nonsense mutation, the correct DNA base has been replaced with a wrong one, and the upshot is that the protein-making machinery, known as the ribosome, runs into a code that it doesn’t recognize; it can’t add an amino acid to the growing protein, and it stops decoding profilaggrin at that point.
If the nonsense mutation occurs early enough, before the first filaggrin unit in FLG, no filaggrin gets made at all.
I believe that with a frameshift mutation (in which one or more DNA bases are missing or added) the protein is very likely to be terminated soon afterward. The end result is the same: little or no filaggrin.
In his 2006 Nature Genetics paper, McLean and his group identified two mutations, R501X (nonsense) and 2282del4 (frameshift), which have turned out to be the most common in Caucasian populations. Both R501X and 2282del4 occur early in the first filaggrin repeat. That means that if you have one such mutation, you will have one good copy of FLG and one bad copy; and if you have mutations on both your copies of FLG, you won’t have any filaggrin at all, and there is a high chance that you have eczema.
Soon after their 2006 discovery, McLean and first author Frances Smith applied for a US patent, “Prevention/treatment of ichthyosis vulgaris, atopy and other disorders.” The patent, number 8,338,386, was granted only recently, on December 25, 2012. It makes many claims, all relating to the ability of five antibiotic drugs, or potentially tRNA molecules, to force the ribosome to read through nonsense mutations.
McLean and Smith’s patent is aimed at the nonsense mutation R501X (they say so in the patent), because it occurs so early in the gene. Such a drug would also work for nonsense mutations later in the sequence.
The drug or agent would not work on frameshift mutations such as 2282del4, as I understand it.
One cool thing about a readthrough drug would be that it would have its strongest effect on people who had nonsense mutations on both copies of FLG. A readthrough drug would theoretically make both copies functional. People with only one mutated copy of FLG would still benefit from having that number increased to two.
In the patent,“atopy” is mentioned in the title and the background information, but neither “atopy” nor “atopic dermatitis” appear in any of the 14 explicit claims. I don’t know whether this matters. I'm not an IP lawyer. It seems curious that the inventors left it out though.
Another curious fact is that only five specific drugs are mentioned: gentamicin, paromomycin, neomycin, tobramycin and negamycin. There is no discussion of the drug discovery process—any tweaking of molecules for greater effect or less toxicity—that I can see. I don’t know whether this matters either.
From what I can tell, McLean’s group has at least one of these compounds, which has most likely been altered from its original structure, in “toxicology” (which means testing in mice, rats, etc.) (see page 16). If you look at this handy graphic provided by the FDA, you will see that toxicology studies are step 2 of 12 in the drug discovery-to-market process. So it is extremely early days and you have to keep in mind that, as I keep saying, almost all drug candidates fail at some stage of clinical testing.
A relevant factor is also that currently there is no FDA-approved drug that acts by this mechanism—by causing the ribosome to ignore nonsense mutations. Ataluren, a drug to cure Duchenne muscular dystrophy and cystic fibrosis, is a readthrough drug in phase III clinical trials. The FDA is apparently especially careful when approving drugs that are “first-in-class,” or the first of their general type. So it is worth following Ataluren’s progress closely; its success could mean that we might see an eczema readthrough drug sooner.
Hat tip to Anonymous (you know who you are)
At least one reader disagreed, and pointed me to a strategy now being developed at the University of Dundee in Scotland: drugs to stimulate or enable filaggrin expression in patients with one or two defective copies of the corresponding gene, FLG. At least one such drug is in the very earliest stages of drug development, toxicology studies in animals. If the drug succeeds in human clinical trials, we might see it in clinics in about 15 years. Potentially, such a drug could help some of the patients most severely affected by eczema.
The best review on filaggrin I’ve seen was co-written by three authors, two of whose names I am familiar with as among the biggest in the field of eczema research: Irwin McLean, who led the team that linked mutations in FLG to increased risk of developing ichthyosis vulgaris and eczema, and Donald Leung, principal investigator of the Atopic Dermatitis Research Network. (The first author is Alan Irvine, a colleague of McLean’s who works in Ireland.)
FLG is a giant, and unusual, gene, one of the last to be sequenced by the Human Genome Project. It encodes an enormous protein, profilaggrin, which contains from 10 to 12 repeats that are cleaved off into individual filaggrin units. Filaggrin itself has several important roles in the upper layers of the skin: it flattens skin cells into their characteristic final shape; it helps bind these cells together into a barrier; and it breaks down into the acidic “natural moisturizing factor.”
Many mutations have been found in FLG. Interestingly, if you take any particular ethnic group (say Japanese), there will be a characteristic profile of mutations for this group that is likely to be different than the profile for another group (say Scottish).
 |
| FLG (read from left to right; red hexagons are filaggrin units.) Common mutations in Asian and European populations. Look how early the nonsense mutation R501X appears. Figure 3A from Irvine, McLean, and Leung's NEJM review |
All filaggrin variants are either “nonsense” or “frameshift” mutations in DNA that encodes protein (as opposed to so-called “junk DNA”). In a nonsense mutation, the correct DNA base has been replaced with a wrong one, and the upshot is that the protein-making machinery, known as the ribosome, runs into a code that it doesn’t recognize; it can’t add an amino acid to the growing protein, and it stops decoding profilaggrin at that point.
If the nonsense mutation occurs early enough, before the first filaggrin unit in FLG, no filaggrin gets made at all.
I believe that with a frameshift mutation (in which one or more DNA bases are missing or added) the protein is very likely to be terminated soon afterward. The end result is the same: little or no filaggrin.
In his 2006 Nature Genetics paper, McLean and his group identified two mutations, R501X (nonsense) and 2282del4 (frameshift), which have turned out to be the most common in Caucasian populations. Both R501X and 2282del4 occur early in the first filaggrin repeat. That means that if you have one such mutation, you will have one good copy of FLG and one bad copy; and if you have mutations on both your copies of FLG, you won’t have any filaggrin at all, and there is a high chance that you have eczema.
Soon after their 2006 discovery, McLean and first author Frances Smith applied for a US patent, “Prevention/treatment of ichthyosis vulgaris, atopy and other disorders.” The patent, number 8,338,386, was granted only recently, on December 25, 2012. It makes many claims, all relating to the ability of five antibiotic drugs, or potentially tRNA molecules, to force the ribosome to read through nonsense mutations.
McLean and Smith’s patent is aimed at the nonsense mutation R501X (they say so in the patent), because it occurs so early in the gene. Such a drug would also work for nonsense mutations later in the sequence.
The drug or agent would not work on frameshift mutations such as 2282del4, as I understand it.
One cool thing about a readthrough drug would be that it would have its strongest effect on people who had nonsense mutations on both copies of FLG. A readthrough drug would theoretically make both copies functional. People with only one mutated copy of FLG would still benefit from having that number increased to two.
In the patent,“atopy” is mentioned in the title and the background information, but neither “atopy” nor “atopic dermatitis” appear in any of the 14 explicit claims. I don’t know whether this matters. I'm not an IP lawyer. It seems curious that the inventors left it out though.
Another curious fact is that only five specific drugs are mentioned: gentamicin, paromomycin, neomycin, tobramycin and negamycin. There is no discussion of the drug discovery process—any tweaking of molecules for greater effect or less toxicity—that I can see. I don’t know whether this matters either.
From what I can tell, McLean’s group has at least one of these compounds, which has most likely been altered from its original structure, in “toxicology” (which means testing in mice, rats, etc.) (see page 16). If you look at this handy graphic provided by the FDA, you will see that toxicology studies are step 2 of 12 in the drug discovery-to-market process. So it is extremely early days and you have to keep in mind that, as I keep saying, almost all drug candidates fail at some stage of clinical testing.
A relevant factor is also that currently there is no FDA-approved drug that acts by this mechanism—by causing the ribosome to ignore nonsense mutations. Ataluren, a drug to cure Duchenne muscular dystrophy and cystic fibrosis, is a readthrough drug in phase III clinical trials. The FDA is apparently especially careful when approving drugs that are “first-in-class,” or the first of their general type. So it is worth following Ataluren’s progress closely; its success could mean that we might see an eczema readthrough drug sooner.
Hat tip to Anonymous (you know who you are)
Tuesday, July 2, 2013
NYC area clinical trial for eczema therapy recruiting participants
A research group at Rockefeller University in New York City seeks participants for a clinical trial of an experimental therapy for atopic dermatitis. See below for details.
Dr. Emma Guttman-Yassky, Dr. Saakshi Khattri and others are exploring whether Stelara (ustekinumab), currently approved in the US for treatment of psoriasis, might benefit patients with moderate to severe AD whose condition has not improved with conventional treatment.
Ustekinumab is a monoclonal antibody to the p40 subunit of the signaling proteins IL-12 and IL-23. It binds to these proteins and prevents them from working. Since IL-12 and IL-23 are involved in the development of certain kinds of T cells, ustekinumab will put a damper on a subset of the T cell arm of the immune system.
I started to speculate about exactly how ustekinumab might work for AD but then I wisely looked at the researchers' own explanation on clinicaltrials.gov. I was only 25% right, so you'd do well to look at their writeup if you're interested.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Randomized Pilot Study of Ustekinumab for Subjects with Chronic Atopic Dermatitis Who Have Sub-optimal Response to Prior Therapy
This study is currently recruiting participants.
Verified March 2013 by Rockefeller University
Sponsor:
Rockefeller University
Information provided by:
Rockefeller University
ClinicalTrials.gov Identifier: NCT01806662
Purpose
We are carrying out a clinical trial with the drug Stelara (ustekinumab), which is already FDA approved for Psoriasis, in patients with moderate to severe eczema, ages 18 years - 75 years. In order to be eligible, a patient must have failed at least topical steroids and either light therapy or oral steroids. Patients will have 15 visits over the course of a year at Rockefeller University, which is located on the Upper East Side of New York City. Patients are guaranteed to receive 3 doses of Stelara throughout the study. Patients will also be allowed to use Triamcinolone 0.025% during the course of the study. If the medication is effective at clearing a patient’s eczema, they will be eligible to receive an extra dose at the completion of the study. For full participation, patients are compensated $600.
Name/Title of the Principal Investigator: Dr. Emma Guttman, MD/PhD
Contact Information:
Saakshi Khattri, MD - Clinical Research Fellow
1230 York Avenue
New York, NY 10065
Business number: 212-327-8354/8333
Fax number: 212-327-8232
Recruitment Office 1-800-782-2737
email: skhattri@rockefeller.edu
For more information, please visit:
http://clinicaltrials.gov/ct2/show/NCT01806662
Dr. Emma Guttman-Yassky, Dr. Saakshi Khattri and others are exploring whether Stelara (ustekinumab), currently approved in the US for treatment of psoriasis, might benefit patients with moderate to severe AD whose condition has not improved with conventional treatment.
Ustekinumab is a monoclonal antibody to the p40 subunit of the signaling proteins IL-12 and IL-23. It binds to these proteins and prevents them from working. Since IL-12 and IL-23 are involved in the development of certain kinds of T cells, ustekinumab will put a damper on a subset of the T cell arm of the immune system.
I started to speculate about exactly how ustekinumab might work for AD but then I wisely looked at the researchers' own explanation on clinicaltrials.gov. I was only 25% right, so you'd do well to look at their writeup if you're interested.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Randomized Pilot Study of Ustekinumab for Subjects with Chronic Atopic Dermatitis Who Have Sub-optimal Response to Prior Therapy
This study is currently recruiting participants.
Verified March 2013 by Rockefeller University
Sponsor:
Rockefeller University
Information provided by:
Rockefeller University
ClinicalTrials.gov Identifier: NCT01806662
Purpose
We are carrying out a clinical trial with the drug Stelara (ustekinumab), which is already FDA approved for Psoriasis, in patients with moderate to severe eczema, ages 18 years - 75 years. In order to be eligible, a patient must have failed at least topical steroids and either light therapy or oral steroids. Patients will have 15 visits over the course of a year at Rockefeller University, which is located on the Upper East Side of New York City. Patients are guaranteed to receive 3 doses of Stelara throughout the study. Patients will also be allowed to use Triamcinolone 0.025% during the course of the study. If the medication is effective at clearing a patient’s eczema, they will be eligible to receive an extra dose at the completion of the study. For full participation, patients are compensated $600.
Name/Title of the Principal Investigator: Dr. Emma Guttman, MD/PhD
Contact Information:
Saakshi Khattri, MD - Clinical Research Fellow
1230 York Avenue
New York, NY 10065
Business number: 212-327-8354/8333
Fax number: 212-327-8232
Recruitment Office 1-800-782-2737
email: skhattri@rockefeller.edu
For more information, please visit:
http://clinicaltrials.gov/ct2/show/NCT01806662
Thursday, June 27, 2013
Surprise: Th2 cells, inflammation high in both allergic, non-allergic eczema
When I talked to Jon Hanifin last year he mentioned an intriguing fact: eczema comes in two general types. About 80% of atopic eczema patients have allergies and high levels of IgE antibodies. But twenty per cent of patients have eczema without allergies.
The technical term for allergic eczema is “extrinsic” atopic dermatitis; the non-allergic kind is “intrinsic” AD.
Production of IgE—and most antibodies—is activated by type 2 helper T cells. So scientists have generally assumed that extrinsic AD patients had overactive type 2 helper T cells. But new research shows that type 2 helper T cells are overactive in both intrinsic and extrinsic AD patients.
The scientists, led by Emma Guttman-Yassky at Rockefeller University in New York City, analyzed skin and blood samples from 42 extrinsic and 9 intrinsic AD patients, looking at molecular and cellular differences in the immune system and the skin.
They found that type 2 helper T cell activation is actually higher in intrinsic AD patients than extrinsic AD patients. In fact, markers of inflammation in general are higher in intrinsic AD.
The results are surprising. Patients with intrinsic AD generally do not go on to develop asthma or allergic rhinitis; yet if you just looked at their helper T cells you’d think they were guaranteed to experience even more severe allergies than those suffered by extrinsic AD patients.
So what's keeping down the IgE levels in intrinsic AD? In the paper, the authors speculate freely, but so far there is no answer.
It also appears that a special class of helper T cells known as type 17 (so-called because they produce the signaling molecule IL-17A) are also more active in intrinsic than extrinsic AD. It’s not clear yet how scientists might use this knowledge to design therapies more specific than current T cell-suppressing options such as ciclosporin, which can have severe side effects.
The research suggests that future T-cell related therapies will likely be similar for intrinsic and extrinsic AD, despite the different nature of the disease in the two patient groups.
Hat tip to KMO.
The technical term for allergic eczema is “extrinsic” atopic dermatitis; the non-allergic kind is “intrinsic” AD.
Production of IgE—and most antibodies—is activated by type 2 helper T cells. So scientists have generally assumed that extrinsic AD patients had overactive type 2 helper T cells. But new research shows that type 2 helper T cells are overactive in both intrinsic and extrinsic AD patients.
The scientists, led by Emma Guttman-Yassky at Rockefeller University in New York City, analyzed skin and blood samples from 42 extrinsic and 9 intrinsic AD patients, looking at molecular and cellular differences in the immune system and the skin.
They found that type 2 helper T cell activation is actually higher in intrinsic AD patients than extrinsic AD patients. In fact, markers of inflammation in general are higher in intrinsic AD.
 |
| Figure 6 from the paper. Scientists now resort to "word clouds" to convey the complexity of molecular biology! |
So what's keeping down the IgE levels in intrinsic AD? In the paper, the authors speculate freely, but so far there is no answer.
It also appears that a special class of helper T cells known as type 17 (so-called because they produce the signaling molecule IL-17A) are also more active in intrinsic than extrinsic AD. It’s not clear yet how scientists might use this knowledge to design therapies more specific than current T cell-suppressing options such as ciclosporin, which can have severe side effects.
The research suggests that future T-cell related therapies will likely be similar for intrinsic and extrinsic AD, despite the different nature of the disease in the two patient groups.
Hat tip to KMO.
Tuesday, June 25, 2013
Not a fan of eczema meta-studies, especially that antibiotics one
You don’t have to look far for an example of how the media can inflate a trivial scientific result into something that looks like important news.
Take last week’s report in the British Journal of Dermatology that exposure of newborns or infants to antibiotics increases the risk of them developing eczema. It was all over the mainstream media, with headlines such as “Report claims antibiotics cause eczema” and “Could Using Antibiotics As A Child Make You Develop Eczema?” I’m still seeing it on Twitter.
I think it’s almost criminally irresponsible to publish news like this when you just know thousands of parents will now hesitate to give their kids antibiotics. The kids will be the ones who suffer needlessly, when they must endure potentially life-threatening infections without treatment.
If giving a child antibiotics substantially increased the risk of developing severe eczema, then that news would be worth paying attention to. But that is not what the BJD paper concludes.
For a start, the paper is a meta-study: a review and summary of a large number of original population studies that other scientists already carried out.
Meta-studies are a great way for scientists to pad their publication records without getting their hands dirty with real research.
In my experience, a meta-study is suspect just because it exists. I don’t see meta-studies coming out in areas in which the science is indisputable (e.g., that UV from the sun causes skin cancer). I see them in areas in which there’s no scientific consensus and most likely the phenomenon under study has a very small real effect. In the field of eczema research, I see meta-studies published about vitamin D, probiotics, traditional Chinese herbal medicine, and so on.
The reason you see meta-studies in these areas is because the trials are all finding different results and someone wants to obtain a big picture of what is going on. Lots of noise and a small signal. If it was obvious what was going on, there’d be no point in a meta-study.
But one major question is how do you compare studies that are done with different aims and measures? This question is especially relevant for the field of eczema research, where there isn’t even a consensus about how to diagnose or measure atopic dermatitis. Not that long ago I went to San Diego as a patient representative to the HOME meeting (the third such get-together), at which researchers were trying to settle on a single standard survey form for measuring how bad a patient’s eczema is. In several meta-studies I have seen the authors mention (i.e. complain) about how difficult it is to draw conclusions from multiple eczema population studies.
Then, the conclusions of the meta-studies are usually weak. The results are almost always presented as “odds ratios,” which to me seem like mathematical sleight-of-hand to inflate very small results. In the antibiotics-early life meta-study, the researchers reported an odds ratio of about 1.4. What this means is you get the number 1.4 when you divide one number, the odds that a child will develop eczema if they get antibiotics, by another number, the odds the child will develop eczema if they are not given antibiotics. If you assume that the second number is about 2:8, or 20% (given that there’s a 20% chance a kid in general will get some kind of eczema) that means, for an odds ratio of 1.4, that there’s a 26% chance a kid given antibiotics will develop eczema.
Big deal, a 6% increase in risk—if you believe the meta-study, which is comparing 20 other studies that all used different methods and measures.
Is that worth risking your child’s life for?
Take last week’s report in the British Journal of Dermatology that exposure of newborns or infants to antibiotics increases the risk of them developing eczema. It was all over the mainstream media, with headlines such as “Report claims antibiotics cause eczema” and “Could Using Antibiotics As A Child Make You Develop Eczema?” I’m still seeing it on Twitter.
I think it’s almost criminally irresponsible to publish news like this when you just know thousands of parents will now hesitate to give their kids antibiotics. The kids will be the ones who suffer needlessly, when they must endure potentially life-threatening infections without treatment.
If giving a child antibiotics substantially increased the risk of developing severe eczema, then that news would be worth paying attention to. But that is not what the BJD paper concludes.
For a start, the paper is a meta-study: a review and summary of a large number of original population studies that other scientists already carried out.
Meta-studies are a great way for scientists to pad their publication records without getting their hands dirty with real research.
In my experience, a meta-study is suspect just because it exists. I don’t see meta-studies coming out in areas in which the science is indisputable (e.g., that UV from the sun causes skin cancer). I see them in areas in which there’s no scientific consensus and most likely the phenomenon under study has a very small real effect. In the field of eczema research, I see meta-studies published about vitamin D, probiotics, traditional Chinese herbal medicine, and so on.
The reason you see meta-studies in these areas is because the trials are all finding different results and someone wants to obtain a big picture of what is going on. Lots of noise and a small signal. If it was obvious what was going on, there’d be no point in a meta-study.
But one major question is how do you compare studies that are done with different aims and measures? This question is especially relevant for the field of eczema research, where there isn’t even a consensus about how to diagnose or measure atopic dermatitis. Not that long ago I went to San Diego as a patient representative to the HOME meeting (the third such get-together), at which researchers were trying to settle on a single standard survey form for measuring how bad a patient’s eczema is. In several meta-studies I have seen the authors mention (i.e. complain) about how difficult it is to draw conclusions from multiple eczema population studies.
Then, the conclusions of the meta-studies are usually weak. The results are almost always presented as “odds ratios,” which to me seem like mathematical sleight-of-hand to inflate very small results. In the antibiotics-early life meta-study, the researchers reported an odds ratio of about 1.4. What this means is you get the number 1.4 when you divide one number, the odds that a child will develop eczema if they get antibiotics, by another number, the odds the child will develop eczema if they are not given antibiotics. If you assume that the second number is about 2:8, or 20% (given that there’s a 20% chance a kid in general will get some kind of eczema) that means, for an odds ratio of 1.4, that there’s a 26% chance a kid given antibiotics will develop eczema.
Big deal, a 6% increase in risk—if you believe the meta-study, which is comparing 20 other studies that all used different methods and measures.
Is that worth risking your child’s life for?
Thursday, June 20, 2013
Three years in: what has the $42M Atopic Dermatitis Research Network produced?
In July it will be three years since the NIH awarded National Jewish Health in Denver, CO $31 million to create and administer the Atopic Dermatitis Research Network, a consortium of five academic sites across the US. A contractor, Rho Federal Systems of Chapel Hill, NC, won an $11 million contract to operate a center to coordinate statistics and clinical trials for the project.
That makes $42 million—spread over five years—which puts the project on the large end of NIH funding for individual biomedical efforts. The typical NIH research grant ranges from $100 thousand to $2 million, and anything bigger is fodder for university news releases. Which raises the question: what have US taxpayers gotten in return?
I ask this as a patient who is grateful that these scientists are working to understand a disease that affects me, my family, and millions in the US and worldwide.
The answer is not obvious, since the publications page on the ADRN website hasn’t been updated since July 2011.
According to the website:
The ADRN’s NIH contract number is HHSN272201000020C. A search in the NIH’s PubMed database returns 12 papers that acknowledge funding by that contract number. Three of those are review papers (which did not involve new research).
So that makes two clinical trials and nine research papers, three years into a five-year $42 million project.
Should US taxpayers expect more; be satisfied; or be impressed?
The answer is probably that we will have to wait to find out.
In each year, a typical top university research lab operates on about $2-3M a year and publishes somewhere around ten papers. That’s roughly $200k a paper.
Three of the five years in the ADRN contract are up; three-fifths of $42M is around $24M. We might therefore naively estimate that we should have seen upwards of 100 papers produced so far.
Most likely the reasons there are only 12 at the moment are that you don't start publishing papers right at the outset of a project. The research must be done first and then written up; and the process of getting accepted to a journal takes months. And the ADRN appears largely to rely on clinical trials--which take time to set up.
So why do we only see two trials listed on clinicaltrials.gov?
I've never had anything to do with a clinical trial, but when I was a researcher, I conducted animal experiments, and there were formidable administrative hurdles to get over before I could start work. I imagine that trials with human subjects are heavily regulated by the government, and for good reason. So the apparently small output of the ADRN to date is, I'm guessing, because it takes a long time to plan trials, get approval, and conduct them, before you can begin analyzing data and reporting it.
Looking at the titles of the published papers, I can't immediately judge which are the most important. So I emailed Donald Leung, the principal investigator for the ADRN (he's a professor and head of the Division of Pediatric Allergy and Immunology at National Jewish Health), and asked him whether he could summarize the consortium’s findings so far and highlight key points. I hope to hear back from him soon and perhaps to interview him on the phone.
I’d like to know what ADRN scientists have found that surprises them. What have they learned that is truly new?
And what is going to be truly useful to patients in the end? Publishing papers should not be the be-all and end-all of scientific research. What about patents? I’d like to know whether anyone in the ADRN has thought about controlling intellectual property and commercialization. While it’s true that clinical studies may highlight the ideal dosing amount or schedule for existing therapies, and this does not involve creating a new commercial enterprise, most medical technology must pass through the marketplace before it can benefit the consumer/patient.
Someone has to do the dirty work of developing scientific discovery into therapy, and it’s not academic scientists.
More to come.
That makes $42 million—spread over five years—which puts the project on the large end of NIH funding for individual biomedical efforts. The typical NIH research grant ranges from $100 thousand to $2 million, and anything bigger is fodder for university news releases. Which raises the question: what have US taxpayers gotten in return?
I ask this as a patient who is grateful that these scientists are working to understand a disease that affects me, my family, and millions in the US and worldwide.
The answer is not obvious, since the publications page on the ADRN website hasn’t been updated since July 2011.
According to the website:
The Atopic Dermatitis Research Network (ADRN) is a consortium of academic medical centers that will conduct clinical research studies in an attempt to learn more about skin infections associated with atopic dermatitis (AD). The studies will focus on antibiotic-resistant Staphylococcus aureus infections and widespread viral infections of the skin, both of which are more prevalent among AD patients. The ADRN will build on the work of the Atopic Dermatitis and Vaccinia Network (ADVN) which conducted clinical studies focused on making smallpox vaccinations safer for people with AD.
This research will lead to a greater understanding of the immune system in AD patients and may lead to novel therapeutic strategies to manage or prevent infectious complications associated with this disease.
The ADRN will conduct a number of clinical studies over the next five years and will be enrolling large numbers of people with AD.A search on clinicaltrials.gov returns two entries for the ADRN: one (open) to create a database of patients for the study of genetic markers connected to susceptibility to infections, and one (completed) to look into how AD patients respond to a new flu vaccine.
The ADRN’s NIH contract number is HHSN272201000020C. A search in the NIH’s PubMed database returns 12 papers that acknowledge funding by that contract number. Three of those are review papers (which did not involve new research).
So that makes two clinical trials and nine research papers, three years into a five-year $42 million project.
Should US taxpayers expect more; be satisfied; or be impressed?
The answer is probably that we will have to wait to find out.
In each year, a typical top university research lab operates on about $2-3M a year and publishes somewhere around ten papers. That’s roughly $200k a paper.
Three of the five years in the ADRN contract are up; three-fifths of $42M is around $24M. We might therefore naively estimate that we should have seen upwards of 100 papers produced so far.
Most likely the reasons there are only 12 at the moment are that you don't start publishing papers right at the outset of a project. The research must be done first and then written up; and the process of getting accepted to a journal takes months. And the ADRN appears largely to rely on clinical trials--which take time to set up.
So why do we only see two trials listed on clinicaltrials.gov?
I've never had anything to do with a clinical trial, but when I was a researcher, I conducted animal experiments, and there were formidable administrative hurdles to get over before I could start work. I imagine that trials with human subjects are heavily regulated by the government, and for good reason. So the apparently small output of the ADRN to date is, I'm guessing, because it takes a long time to plan trials, get approval, and conduct them, before you can begin analyzing data and reporting it.
Looking at the titles of the published papers, I can't immediately judge which are the most important. So I emailed Donald Leung, the principal investigator for the ADRN (he's a professor and head of the Division of Pediatric Allergy and Immunology at National Jewish Health), and asked him whether he could summarize the consortium’s findings so far and highlight key points. I hope to hear back from him soon and perhaps to interview him on the phone.
I’d like to know what ADRN scientists have found that surprises them. What have they learned that is truly new?
And what is going to be truly useful to patients in the end? Publishing papers should not be the be-all and end-all of scientific research. What about patents? I’d like to know whether anyone in the ADRN has thought about controlling intellectual property and commercialization. While it’s true that clinical studies may highlight the ideal dosing amount or schedule for existing therapies, and this does not involve creating a new commercial enterprise, most medical technology must pass through the marketplace before it can benefit the consumer/patient.
Someone has to do the dirty work of developing scientific discovery into therapy, and it’s not academic scientists.
More to come.
Tuesday, June 18, 2013
Supreme Court gene patent decision means little for eczema research
Following last week’s decision by the US Supreme Court that human genes cannot be patented, I’d say nothing has changed for eczema patients.
What I mean is that it makes little difference to eczema therapies now or in the future whether companies can obtain US patents on human genes.
I see two major issues: moral and commercial. Morally, I feel it’s a great triumph that even the famously conservative justices of the Supreme Court—who we really expected to side with big bucks, as they seem reliably to do—unanimously affirmed that nobody can own naturally-occurring human DNA. No company can own a piece of my genetic heritage.
Commercially, the issue is intellectual property. I work in biotech, and every day I hear about how it’s crucial for companies to control their IP. No investor is going to back a company that can obviously be sued in the future or that is developing a product that could instantly be copied by a competitor without penalty.
The loser in the decision was Myriad Genetics, which owned the US patent on BRCA1 and BRCA2, two human genes in which mutations increase one’s chances of getting breast cancer. (From what I can tell, Myriad had patents on the normal genes as well as common cancer-linked mutations.) Myriad had exclusive rights to DNA tests that could determine whether patients had mutations. Now many other companies are developing similar tests, and the competition will drive down the price of the tests.
That’s great if you want to get tested for breast cancer. But what does it mean for companies that are developing diagnostic tests for other conditions? These companies may abandon their efforts. Or the companies may never get started.
At least that is what one commercially-minded person whose views I respect tells me.
The Faster Cures blog, conversely, makes the point that patenting DNA could, and has, led to R&D on diseases being blocked by legal obstruction. Lilly, apparently, spent eight years fighting Harvard, MIT and others over the rights to one particular gene, NF-kB. Presumably lots of money got spent that might have gone to actual research instead of lawyers.
But for a gene patent to be useful, there must first of all be a strong link between genetics and disease. Eczema, despite being known to have a strong genetic component, has not been definitively linked to genes except in the case of filaggrin. There are a few mutations that seem to correspond to particularly severe eczema but they don’t occur in many people.
In any case, the sequence of filaggrin was made public in 2006 so the point is moot—once made public, an invention can’t be patented. (I searched the US Patent and Trademark Office database and didn’t see anything.)
Also a diagnostic test is only useful if it gives you information you can act on. There’s no point telling an adult that they have severe eczema, because they already know that. And if parents learn that their child is at risk—not guaranteed—of developing eczema, what can they do to prevent it?
Not much that I know of.
Diagnostics aside, how might a gene patent be useful?
Many drugs or biotherapies being developed affect how genes are regulated—how the process of turning their information into protein is amplified or damped. Perhaps owning a gene patent would let you control work that other people are doing to regulate that gene. We’ll never know now! What is certain, though, is that if you had a gene patent and lots of money, you could probably intimidate other companies by threatening them with expensive legal action.
I don’t think enough is known about eczema at this point that a gene patent would have been a factor. Look at the existing therapies and the few in the pipeline (such as Anacor’s). They are all either anti-inflammatories or calcineurin inhibitors. They don’t affect genes directly.
Researchers are starting to put together useful models of how itch signals get transmitted from the skin to the brain. For itch, we wouldn’t be interested in a diagnostic, but we would like to have a therapy. It’s conceivable that one or two genes may turn out to be key, and we might want drugs to regulate them. But gene patents would not be necessary for scientists or companies to do that work.
In short: last week’s Supreme Court decision, while morally important and laudable, will have little effect on the field of eczema research and therapy.
What I mean is that it makes little difference to eczema therapies now or in the future whether companies can obtain US patents on human genes.
I see two major issues: moral and commercial. Morally, I feel it’s a great triumph that even the famously conservative justices of the Supreme Court—who we really expected to side with big bucks, as they seem reliably to do—unanimously affirmed that nobody can own naturally-occurring human DNA. No company can own a piece of my genetic heritage.
Commercially, the issue is intellectual property. I work in biotech, and every day I hear about how it’s crucial for companies to control their IP. No investor is going to back a company that can obviously be sued in the future or that is developing a product that could instantly be copied by a competitor without penalty.
The loser in the decision was Myriad Genetics, which owned the US patent on BRCA1 and BRCA2, two human genes in which mutations increase one’s chances of getting breast cancer. (From what I can tell, Myriad had patents on the normal genes as well as common cancer-linked mutations.) Myriad had exclusive rights to DNA tests that could determine whether patients had mutations. Now many other companies are developing similar tests, and the competition will drive down the price of the tests.
That’s great if you want to get tested for breast cancer. But what does it mean for companies that are developing diagnostic tests for other conditions? These companies may abandon their efforts. Or the companies may never get started.
At least that is what one commercially-minded person whose views I respect tells me.
The Faster Cures blog, conversely, makes the point that patenting DNA could, and has, led to R&D on diseases being blocked by legal obstruction. Lilly, apparently, spent eight years fighting Harvard, MIT and others over the rights to one particular gene, NF-kB. Presumably lots of money got spent that might have gone to actual research instead of lawyers.
But for a gene patent to be useful, there must first of all be a strong link between genetics and disease. Eczema, despite being known to have a strong genetic component, has not been definitively linked to genes except in the case of filaggrin. There are a few mutations that seem to correspond to particularly severe eczema but they don’t occur in many people.
In any case, the sequence of filaggrin was made public in 2006 so the point is moot—once made public, an invention can’t be patented. (I searched the US Patent and Trademark Office database and didn’t see anything.)
Also a diagnostic test is only useful if it gives you information you can act on. There’s no point telling an adult that they have severe eczema, because they already know that. And if parents learn that their child is at risk—not guaranteed—of developing eczema, what can they do to prevent it?
Not much that I know of.
Diagnostics aside, how might a gene patent be useful?
Many drugs or biotherapies being developed affect how genes are regulated—how the process of turning their information into protein is amplified or damped. Perhaps owning a gene patent would let you control work that other people are doing to regulate that gene. We’ll never know now! What is certain, though, is that if you had a gene patent and lots of money, you could probably intimidate other companies by threatening them with expensive legal action.
I don’t think enough is known about eczema at this point that a gene patent would have been a factor. Look at the existing therapies and the few in the pipeline (such as Anacor’s). They are all either anti-inflammatories or calcineurin inhibitors. They don’t affect genes directly.
Researchers are starting to put together useful models of how itch signals get transmitted from the skin to the brain. For itch, we wouldn’t be interested in a diagnostic, but we would like to have a therapy. It’s conceivable that one or two genes may turn out to be key, and we might want drugs to regulate them. But gene patents would not be necessary for scientists or companies to do that work.
In short: last week’s Supreme Court decision, while morally important and laudable, will have little effect on the field of eczema research and therapy.
Wednesday, June 12, 2013
Scientists identify two classes of itch neuron by turning them off separately
For several years it’s been known that itch and pain signals from the skin are carried by different types of neuron to the spinal cord and brain. But there's more than one kind of itch. Scientists have now clearly identified at least two types of itch neuron—one that responds to histamine and a second type that responds to other itch-provoking molecules.
These results could lead to drugs that selectively shut down chronic itch in eczema patients but leave the rest of the sensory system intact.
Some itch is caused by histamine, which triggers an itch signal in certain neurons. But histamine is not the main source of itch for eczema patients. In eczema, most itch has its origins in allergy, when mast cells release “pruritogens” that bind to receptors on itch neurons.
For a long time it was an open question whether histamine and the other pruritogens were triggering itch signals in the same neurons, or different types that scientists could distinguish experimentally.
In late May, researchers led by Alexander Binshtok at the Hebrew University in Jerusalem and Clifford Woolf at Harvard Medical School reported results that clearly showed histamine and non-histamine itch signals are carried by different neurons. The research was published in the journal Nature Neuroscience.
The scientists used a novel two-stage experimental technique to shut the two neuron types down independently. Perhaps someday a similar technique might be embodied in an anti-itch therapy.
What they did was to exploit the fact that when neurons detect histamine and pruritogens, large-diameter channels open in the neurons to let in ions (charged particles) that initiate the electrochemical itch signal, which relies on sodium and potassium.
First, the scientists treated mice with either histamine or a non-histamine pruritogen. At the same time they injected the mice with QX-314, a molecule that blocks sodium ion channels (which are very small-diameter). The large-bore ion channels opened to let in sodium, potassium, and QX-314.
Thereafter, those neurons were unable to fire itch signals, because their sodium channels were blocked by QX-314. The scientists showed that when they dosed the mice with histamine and QX-314, one group of neurons didn’t work (and the mice didn't scratch). When they dosed the mice with other pruritogens and QX-314, the histamine itch neurons worked, but other subsets of neurons were shut off (and the mice didn't scratch).
The scientists’ technique is not directly translatable to therapy, because this study was conducted in mice and involved injection, which is not practical for daily use. But the molecular action they were studying takes place in the upper skin layers, and one could imagine that someday a cream or ointment might be developed that would include two components: one to open large-bore ion channels that detect pruritogens, and another to block the electrochemical signals in those neurons.
Hat tip to Ryan.
PS in a recent post I discussed the difference between TRPV1 ion channels, required for histamine itch, and TRPA1 channels, required for chronic itch. These are the "large-bore" channels mentioned above. Trivia: To trigger a histamine itch signal in a neuron, histamine must activate both TRPV1 and the H1 histamine receptor. To trigger a non-histamine itch signal in a neuron, a pruritogen must activate both TRPA1 and a special pruritogen receptor--"MrgprC11" in the case of dry skin.
These results could lead to drugs that selectively shut down chronic itch in eczema patients but leave the rest of the sensory system intact.
Some itch is caused by histamine, which triggers an itch signal in certain neurons. But histamine is not the main source of itch for eczema patients. In eczema, most itch has its origins in allergy, when mast cells release “pruritogens” that bind to receptors on itch neurons.
For a long time it was an open question whether histamine and the other pruritogens were triggering itch signals in the same neurons, or different types that scientists could distinguish experimentally.
In late May, researchers led by Alexander Binshtok at the Hebrew University in Jerusalem and Clifford Woolf at Harvard Medical School reported results that clearly showed histamine and non-histamine itch signals are carried by different neurons. The research was published in the journal Nature Neuroscience.
The scientists used a novel two-stage experimental technique to shut the two neuron types down independently. Perhaps someday a similar technique might be embodied in an anti-itch therapy.
What they did was to exploit the fact that when neurons detect histamine and pruritogens, large-diameter channels open in the neurons to let in ions (charged particles) that initiate the electrochemical itch signal, which relies on sodium and potassium.
First, the scientists treated mice with either histamine or a non-histamine pruritogen. At the same time they injected the mice with QX-314, a molecule that blocks sodium ion channels (which are very small-diameter). The large-bore ion channels opened to let in sodium, potassium, and QX-314.
Thereafter, those neurons were unable to fire itch signals, because their sodium channels were blocked by QX-314. The scientists showed that when they dosed the mice with histamine and QX-314, one group of neurons didn’t work (and the mice didn't scratch). When they dosed the mice with other pruritogens and QX-314, the histamine itch neurons worked, but other subsets of neurons were shut off (and the mice didn't scratch).
The scientists’ technique is not directly translatable to therapy, because this study was conducted in mice and involved injection, which is not practical for daily use. But the molecular action they were studying takes place in the upper skin layers, and one could imagine that someday a cream or ointment might be developed that would include two components: one to open large-bore ion channels that detect pruritogens, and another to block the electrochemical signals in those neurons.
Hat tip to Ryan.
PS in a recent post I discussed the difference between TRPV1 ion channels, required for histamine itch, and TRPA1 channels, required for chronic itch. These are the "large-bore" channels mentioned above. Trivia: To trigger a histamine itch signal in a neuron, histamine must activate both TRPV1 and the H1 histamine receptor. To trigger a non-histamine itch signal in a neuron, a pruritogen must activate both TRPA1 and a special pruritogen receptor--"MrgprC11" in the case of dry skin.
Friday, June 7, 2013
Daughter is allergic to sesame, horses. Horses!?
Unfortunately medicine is still far from the Star Trek tricorder stage, at which you can just wave your iPhone over someone and tell what they’re allergic to, but the next best thing is specific IgE testing. We got my daughter V’s results back today. I found the process and fascinating and the outcome illuminating.
IgE are the antibodies responsible for allergy. The IgE results we got consisted of an antibody quantity in units/ml (whatever “units” are), plus a “class” (from 0 to VI) which indicates the degree of allergy. Class can range from “negative” to “extremely high positive.”
Now, I need to talk to an allergist to figure out what is meant by “class”. It seems to be a value that a clinician makes a guess at based on the IgE measurement and the patient’s medical history and, possibly, the allergen in question. From what I can tell the class reported can vary depending on the assay and the person doing the estimating.
The results:
V is apparently moderately allergic to peanut (3.7 U/ml, class III) and almond (2.5 U/ml, class II) so tree nuts are still out.
She’s allergic to milk (8.3 U/ml, class III), which we know all too well, since only last week I gave her milk by accident and she spent the next half hour barfing on the kitchen floor.
Quite a surprise to find out was that her highest antibody level is to sesame (14.7 U/ml, class III). I once gave her sesame sticks once and she vomited. I gave her a sesame bagel and she said her stomach hurt. But she’s been happily eating pressed sheets of nori (seaweed) that apparently contain sesame oil. Anyway, from now on: no sesame!
And here’s the funny thing. Along with her brother, she gets horse-riding lessons every two weeks. She comes back from them all blotchy in the face. We thought it might be from grass pollen, but on a whim my wife had her tested for allergy to “horse dander.” And she tested positive (3.4 U/ml, class II)!
But no allergy to rye grass pollen.
Allergic to horses. Who knew. Well, that ought to be an easy one to avoid. And it’ll give me a great excuse when she starts demanding a pony for her birthday.
IgE are the antibodies responsible for allergy. The IgE results we got consisted of an antibody quantity in units/ml (whatever “units” are), plus a “class” (from 0 to VI) which indicates the degree of allergy. Class can range from “negative” to “extremely high positive.”
Now, I need to talk to an allergist to figure out what is meant by “class”. It seems to be a value that a clinician makes a guess at based on the IgE measurement and the patient’s medical history and, possibly, the allergen in question. From what I can tell the class reported can vary depending on the assay and the person doing the estimating.
The results:
V is apparently moderately allergic to peanut (3.7 U/ml, class III) and almond (2.5 U/ml, class II) so tree nuts are still out.
She’s allergic to milk (8.3 U/ml, class III), which we know all too well, since only last week I gave her milk by accident and she spent the next half hour barfing on the kitchen floor.
Quite a surprise to find out was that her highest antibody level is to sesame (14.7 U/ml, class III). I once gave her sesame sticks once and she vomited. I gave her a sesame bagel and she said her stomach hurt. But she’s been happily eating pressed sheets of nori (seaweed) that apparently contain sesame oil. Anyway, from now on: no sesame!
And here’s the funny thing. Along with her brother, she gets horse-riding lessons every two weeks. She comes back from them all blotchy in the face. We thought it might be from grass pollen, but on a whim my wife had her tested for allergy to “horse dander.” And she tested positive (3.4 U/ml, class II)!
But no allergy to rye grass pollen.
Allergic to horses. Who knew. Well, that ought to be an easy one to avoid. And it’ll give me a great excuse when she starts demanding a pony for her birthday.
Thursday, June 6, 2013
Allergy testing reminds me how little I know about medicine
Yesterday my daughter V went in for what has become a yearly ritual: her specific IgE blood test. She bravely went in after listening to the previous patient scream for 20 minutes. She yelped when she was stuck, but gritted it out while the nurse drew four vials of blood.
Four vials seems like a lot. My wife, who is a veterinarian, says she only takes one vial to test dogs for multiple allergens.
The process reminds me how little I know about medicine in practice.
IgE is a type of antibody, a Y-shaped molecule with sticky ends that recognizes allergens and triggers inflammation. Kaiser Permanente, our HMO, uses the ELISA test to measure IgE levels, instead of RAST, which has been abandoned since 2010 because it involves using radioactive material.
The first result came back as “IgE, QN 368 Standard range 0 - 75 U/mL”
"U" is for "unit." How many antibodies in a unit? I have no idea. The internet is no help here. 368 U/ml, from what I can tell, is her measure of total IgE, all the antibodies of this type she has circulating in her blood.
So that means V's IgE is five times the maximum normal limit. That’s typical for someone with atopy.
We’re still waiting for the specific results. I wouldn’t put it past Kaiser to waste at least one vial doing the wrong test, and then tell us we need to come in and give more blood.
Last year, among other things, V tested positive for IgE against milk, with 7.8 U/mL. I find it remarkable that her titer of antibodies to milk is 10% of the maximum number of antibodies that a “normal” person should have against everything.
V has eczema and mild asthma. Positive IgE tests are no guarantee of allergy, but we know she’s allergic to milk, since she vomits every time we give it to her. (Our son has no allergies and my wife and I have accidentally switched the kids’ glasses at lunch. Oops.)
She also has consistently tested positive for peanut and walnut allergy (and beef!), though there are as yet no incidents where she’s eaten some and had a reaction. We’re just trying to keep tabs on her allergies as she grows up, hoping, of course, that they will go away—but also fearing that she could develop a life-threatening allergy.
Four vials seems like a lot. My wife, who is a veterinarian, says she only takes one vial to test dogs for multiple allergens.
The process reminds me how little I know about medicine in practice.
IgE is a type of antibody, a Y-shaped molecule with sticky ends that recognizes allergens and triggers inflammation. Kaiser Permanente, our HMO, uses the ELISA test to measure IgE levels, instead of RAST, which has been abandoned since 2010 because it involves using radioactive material.
The first result came back as “IgE, QN 368 Standard range 0 - 75 U/mL”
"U" is for "unit." How many antibodies in a unit? I have no idea. The internet is no help here. 368 U/ml, from what I can tell, is her measure of total IgE, all the antibodies of this type she has circulating in her blood.
So that means V's IgE is five times the maximum normal limit. That’s typical for someone with atopy.
We’re still waiting for the specific results. I wouldn’t put it past Kaiser to waste at least one vial doing the wrong test, and then tell us we need to come in and give more blood.
Last year, among other things, V tested positive for IgE against milk, with 7.8 U/mL. I find it remarkable that her titer of antibodies to milk is 10% of the maximum number of antibodies that a “normal” person should have against everything.
V has eczema and mild asthma. Positive IgE tests are no guarantee of allergy, but we know she’s allergic to milk, since she vomits every time we give it to her. (Our son has no allergies and my wife and I have accidentally switched the kids’ glasses at lunch. Oops.)
She also has consistently tested positive for peanut and walnut allergy (and beef!), though there are as yet no incidents where she’s eaten some and had a reaction. We’re just trying to keep tabs on her allergies as she grows up, hoping, of course, that they will go away—but also fearing that she could develop a life-threatening allergy.
Tuesday, June 4, 2013
Key to chronic eczema itch may lie in special ion channel
Recently scientists reported the discovery of an “itch molecule” (Nppb) responsible for conveying the itch signal across the synapse from sensory neurons in the skin to neurons in the dorsal horn of the spinal cord.
The media made a great deal of this study, which laid out a substantial model for how we feel itch.
Something I hadn’t noticed, though, was that the Science study considered only a subset of neurons involved in sensing itch—those that are activated by histamine. These neurons, at the itch-sensing end, have a type of ion channel called “TRPV1” that detects histamine and other substances, or “pruritogens,” that induce itch.
An ion channel is a kind of gate that opens when a key--such as a histamine molecule--binds to it. The open gate lets in sodium or potassium ions. When this happens to ion channels in a neuron, the neuron sends an electrical pulse down its length, transmitting information, such as a sensation of itch.
But there are other triggers for itch besides histamine. “Histamine-independent” itch is particularly important in the chronic itch experienced by eczema patients. (And that's why antihistamines don't do us any good.)
Histamine-independent itch is transmitted by neurons that possess TRPA1 ion channels. A new study, published in the Journal of Neuroscience, shows that mice only feel chronic itch if they have neurons expressing TRPA1 channels. Strikingly, the scientists show that knocking out TRPV1 channels (the histamine-dependent kind) does not affect the ability of mice to feel chronic itch.
As a model of chronic itch, the researchers shaved the cheeks of lab mice and exposed the skin to drying chemicals over a period of a few days. The mice scratched their cheeks and developed classic signs of dry, itchy skin--unless their TRPA1 channels had either been genetically deleted or inhibited by a drug,in which cases they hardly scratched at all.
The researchers were also interested in whether the itch-scratch cycle affected the sensation of itch. If you don’t scratch an itch, does it get better or worse? The answer appears to be that if you (or, by proxy, a lab mouse) have an itch on your back that you can only scratch by rubbing it against the wall, it may torment you, but when measured by objective standards, skin that you don’t scratch ends up in better shape.
We can draw two practical conclusions from this work, which was led by Diana Bautista at UC Berkeley: that blocking TRPA1 channels with a drug in cream or ointment form could be a potential solution to the chronic itch of eczema; and that it really does appear that if you can break the itch-scratch cycle, your skin will be better off.
Now, we all know how difficult it is to stop scratching. It’s not as easy as saying that you’ll stop. But this type of research certainly highlights the positive feedback of habit-reversal, which uses psychiatric techniques to reduce habitual scratching. Scratch less…and you’ll feel less itchy.
I do have one question: does the molecule Nppb, reported in the Science paper two weeks ago, transmit chronic itch signals as well as histamine-induced itch? If so, it is still a valuable target for further research into eczema therapies.
The media made a great deal of this study, which laid out a substantial model for how we feel itch.
Something I hadn’t noticed, though, was that the Science study considered only a subset of neurons involved in sensing itch—those that are activated by histamine. These neurons, at the itch-sensing end, have a type of ion channel called “TRPV1” that detects histamine and other substances, or “pruritogens,” that induce itch.
An ion channel is a kind of gate that opens when a key--such as a histamine molecule--binds to it. The open gate lets in sodium or potassium ions. When this happens to ion channels in a neuron, the neuron sends an electrical pulse down its length, transmitting information, such as a sensation of itch.
But there are other triggers for itch besides histamine. “Histamine-independent” itch is particularly important in the chronic itch experienced by eczema patients. (And that's why antihistamines don't do us any good.)
Histamine-independent itch is transmitted by neurons that possess TRPA1 ion channels. A new study, published in the Journal of Neuroscience, shows that mice only feel chronic itch if they have neurons expressing TRPA1 channels. Strikingly, the scientists show that knocking out TRPV1 channels (the histamine-dependent kind) does not affect the ability of mice to feel chronic itch.
As a model of chronic itch, the researchers shaved the cheeks of lab mice and exposed the skin to drying chemicals over a period of a few days. The mice scratched their cheeks and developed classic signs of dry, itchy skin--unless their TRPA1 channels had either been genetically deleted or inhibited by a drug,in which cases they hardly scratched at all.
The researchers were also interested in whether the itch-scratch cycle affected the sensation of itch. If you don’t scratch an itch, does it get better or worse? The answer appears to be that if you (or, by proxy, a lab mouse) have an itch on your back that you can only scratch by rubbing it against the wall, it may torment you, but when measured by objective standards, skin that you don’t scratch ends up in better shape.
We can draw two practical conclusions from this work, which was led by Diana Bautista at UC Berkeley: that blocking TRPA1 channels with a drug in cream or ointment form could be a potential solution to the chronic itch of eczema; and that it really does appear that if you can break the itch-scratch cycle, your skin will be better off.
Now, we all know how difficult it is to stop scratching. It’s not as easy as saying that you’ll stop. But this type of research certainly highlights the positive feedback of habit-reversal, which uses psychiatric techniques to reduce habitual scratching. Scratch less…and you’ll feel less itchy.
I do have one question: does the molecule Nppb, reported in the Science paper two weeks ago, transmit chronic itch signals as well as histamine-induced itch? If so, it is still a valuable target for further research into eczema therapies.
Thursday, May 30, 2013
Turns out Protopic and Elidel carry no cancer risk
If you’ve ever considered using Protopic or Elidel as an alternative to steroids, you, like me, will have been taken aback by the FDA’s black-box warning that these drugs theoretically could increase your risk of getting cancer. (In the US, there's an actual black box on the packaging, somewhat more prominent than the warning on cigarette packs.)
A new, well-written report debunks this claim thoroughly.
Written by two researchers at Saint Louis University in Missouri and UT Medical School in Texas and a science writer in Chicago, and published in the American Journal of Clinical Dermatology, the paper points out that the FDA’s 2005 advisory was based on three justifications: extensive off-label use to treat children under two years old; a very small number of adverse drug reports (two for Elidel and five for Protopic); and a study done in monkeys in which the animals were given much larger doses than would be typical for human patients.
Now, eight years after the first FDA warnings appeared, the authors say that use of these creams has not been shown to increase a patient’s risk of developing any type of cancer.
Elidel (pimecrolimus) and Protopic (tacrolimus) are “calcineurin inhibitors” formulated as creams. They reduce the levels of pro-inflammatory molecules produced by T cells. With all immune-suppressant drugs there is always a possibility that the drug will prevent the body from destroying cells that have become malignant. But Elidel and Protopic do not raise the risk above the background level.
Unlike topical steroids, calcineurin inhibitors do not thin the skin, and patients who use them apparently do not experience a “rebound” effect in which the eczema returns after drug use stops, as is the case with steroids.
According to a graph in the report, Elidel sales are now much lower than they were in 2005, while Protopic sales have recovered to their original levels.
This matters because calcineurin inhibitors are a valuable alternative to steroids—for some, at least. When I tried Elidel, it did nothing for me, and Protopic gave me an intense burning sensation and a terrible headache.
So if you have been putting off using these drugs for fear they might cause cancer—now’s the time to give them a try!
A new, well-written report debunks this claim thoroughly.
Written by two researchers at Saint Louis University in Missouri and UT Medical School in Texas and a science writer in Chicago, and published in the American Journal of Clinical Dermatology, the paper points out that the FDA’s 2005 advisory was based on three justifications: extensive off-label use to treat children under two years old; a very small number of adverse drug reports (two for Elidel and five for Protopic); and a study done in monkeys in which the animals were given much larger doses than would be typical for human patients.
Now, eight years after the first FDA warnings appeared, the authors say that use of these creams has not been shown to increase a patient’s risk of developing any type of cancer.
Elidel (pimecrolimus) and Protopic (tacrolimus) are “calcineurin inhibitors” formulated as creams. They reduce the levels of pro-inflammatory molecules produced by T cells. With all immune-suppressant drugs there is always a possibility that the drug will prevent the body from destroying cells that have become malignant. But Elidel and Protopic do not raise the risk above the background level.
Unlike topical steroids, calcineurin inhibitors do not thin the skin, and patients who use them apparently do not experience a “rebound” effect in which the eczema returns after drug use stops, as is the case with steroids.
According to a graph in the report, Elidel sales are now much lower than they were in 2005, while Protopic sales have recovered to their original levels.
This matters because calcineurin inhibitors are a valuable alternative to steroids—for some, at least. When I tried Elidel, it did nothing for me, and Protopic gave me an intense burning sensation and a terrible headache.
So if you have been putting off using these drugs for fear they might cause cancer—now’s the time to give them a try!
Tuesday, May 28, 2013
"Itch molecule" discovery a big step forward
All over the media last week was the news that two scientists at the National Institutes of Health in Bethesda, MD had discovered “the molecule responsible for itch.”
This molecule, “Nppb,” relays signals from certain neurons that detect itch in the skin to other neurons that carry the signals up the spinal cord to the brain. The scientists, Santosh Mishra and Mark Hoon, engineered mice in which the gene for Nppb had been turned off. The mice could not, apparently, feel itch.
The media hype is evident. Nppb is not THE molecule responsible for itch. Several molecules are known to be involved in detecting itch in the first place, and we know many others must be involved in the signaling pathway.
What is remarkable, though, is that the scientists were able to define a model for how itch gets from the skin to the spinal cord.
We now know that there are at least two pinch points: the synapse across which Nppb carries the signal, and a second downstream synapse across which another molecule, GRP, sends the information to the next stage of neurons.
Blocking the receptors for Nppb or GRP would seem to be a prime candidate for an anti-itch therapy.
But, of course, there are complications. Nppb was originally known because it is important in the heart, where it controls blood pressure. GRP controls digestion. The genetically engineered Nppb-free mice died early. (The scientists said so in their media interviews.)
So you can’t just take a pill that blocks Nppb receptors everywhere. That would be a disaster.
But this kind of restriction on where a drug can act is well-known in pharmacology. That’s why, e.g., I can use the anti-pain Voltaren gel (diclofenac) safely by rubbing it into my joints, but diclofenac is known to be pretty toxic if you swallow it.
You can’t design an Nppb receptor-blocking topical cream, because the important synapses are in the spinal cord. A cream would only be effective on the surface.
But it might be possible to take a pill that blocks Nppb only in the spinal cord. I’m not sure how, but that’s what major pharma companies are paying their scientists the big bucks to find out. Maybe the receptors in the spinal cord are subtly different than those elsewhere in the body.
This is very exciting stuff. The massive question is whether the work applies to humans. I would expect it did. Mice and human immune systems are quite different, but our nervous systems are not. We most likely have an analog of Nppb that carries our itch signals.
Just to put this in context—the new work tells us substantially more about itch signaling than previous work in the field. I’d been aware of studies that had identified a class of itch neurons, or certain molecules important in detecting itch in the skin, but this research builds on those foundations in a big way.
This molecule, “Nppb,” relays signals from certain neurons that detect itch in the skin to other neurons that carry the signals up the spinal cord to the brain. The scientists, Santosh Mishra and Mark Hoon, engineered mice in which the gene for Nppb had been turned off. The mice could not, apparently, feel itch.
The media hype is evident. Nppb is not THE molecule responsible for itch. Several molecules are known to be involved in detecting itch in the first place, and we know many others must be involved in the signaling pathway.
What is remarkable, though, is that the scientists were able to define a model for how itch gets from the skin to the spinal cord.
 |
| Mishra and Hoon's model of how neurons carry the itch signal. (Fig 4G from their Science paper.) |
We now know that there are at least two pinch points: the synapse across which Nppb carries the signal, and a second downstream synapse across which another molecule, GRP, sends the information to the next stage of neurons.
Blocking the receptors for Nppb or GRP would seem to be a prime candidate for an anti-itch therapy.
But, of course, there are complications. Nppb was originally known because it is important in the heart, where it controls blood pressure. GRP controls digestion. The genetically engineered Nppb-free mice died early. (The scientists said so in their media interviews.)
So you can’t just take a pill that blocks Nppb receptors everywhere. That would be a disaster.
But this kind of restriction on where a drug can act is well-known in pharmacology. That’s why, e.g., I can use the anti-pain Voltaren gel (diclofenac) safely by rubbing it into my joints, but diclofenac is known to be pretty toxic if you swallow it.
You can’t design an Nppb receptor-blocking topical cream, because the important synapses are in the spinal cord. A cream would only be effective on the surface.
But it might be possible to take a pill that blocks Nppb only in the spinal cord. I’m not sure how, but that’s what major pharma companies are paying their scientists the big bucks to find out. Maybe the receptors in the spinal cord are subtly different than those elsewhere in the body.
This is very exciting stuff. The massive question is whether the work applies to humans. I would expect it did. Mice and human immune systems are quite different, but our nervous systems are not. We most likely have an analog of Nppb that carries our itch signals.
Just to put this in context—the new work tells us substantially more about itch signaling than previous work in the field. I’d been aware of studies that had identified a class of itch neurons, or certain molecules important in detecting itch in the skin, but this research builds on those foundations in a big way.
Thursday, May 23, 2013
TopMD conducts clinical trial of CLn Bodywash for marketing purposes
CLn Bodywash, the “bleach bath in a can,” sounds like a product that we all need—a quick and easy way to cleanse your skin of Staphylococcus aureus and other nasty bacteria associated with eczema. But the marketing campaign arranged by CLn’s maker, Dallas-based TopMD, could be better.
For a start, they could arrange a decent clinical trial.
CLn must be classified as a cosmetic and not a medical product, because the FDA didn’t require tests before CLn hit the stores.
You would think the usual way to proceed with a medical product would be:
1) clinical trial to prove safe and effective
2) manufacturing and marketing
But TopMD scientists recently published the results of a clinical trial for CLn in the journal Pediatric Dermatology, about nine months after I first heard the product was for sale.
Of course dilute bleach baths are a known household treatment to manage skin bacteria. CLn is a portable bleach bath and isn't going to be any more hazardous than what thousands of people are already doing in their bathtubs. But is it any better? Is it worth paying money for?
I think that some marketing analyst decided that doctors around the US were reluctant to buy or recommend CLn because it hadn’t undergone a clinical trial. Now it has—with the shiny label “peer-reviewed,” although the journal it was published in is low-impact, and the “peer” who deemed the study worthy of publication could well have been a single graduate student.
The study might possibly qualify as a “phase 0” trial. It’s conducted on 18 subjects all of whom are given the product. There’s no control group that receives a placebo.
This is a problem, because both the doctors conducting the trial and the patients both want the product to work. So the reported results are bound to look better than they really are. Scientifically, this study is far from the final word on whether CLn is truly effective.
The way to avoid this problem is to have a double-blind randomized control trial where, at the very least, half of the patients get CLn and half get something that looks like it but isn’t, and nobody knows which is which until the results have been recorded.
For an example of how this might be done, at least in a way that looks good from a marketing perspective, you can see that the makers of DermaSilk clothing appear to get it right in their studies, the most recent of which was published online this week.
That the recent CLn study was motivated by marketing is clear from one of its measures. Participants were asked “Would you recommend CLn to a friend?” This is not a data point you see in too many scientific papers.
The company’s press release quotes UC San Diego’s Dr. Larry Eichenfield, chief of pediatric and adolescent dermatology at Children's Hospital, San Diego—a world leader in the field. Eichenfield says “I am excited to read the study by Dr. Ryan et al showing the benefits of TopMD's sodium hypochlorite-based body wash.”
The release doesn’t mention that Eichenfield sits on TopMD’s medical board.
I like the idea of CLn, and I think it’s probably a valuable product. I’m happy they sent me a free bottle to review back in October, and I’m keeping it in case I need it. But I wish they could present some more convincing evidence that it works. Are they afraid that it doesn’t? If not, why not use a control group in the study?
For a start, they could arrange a decent clinical trial.
CLn must be classified as a cosmetic and not a medical product, because the FDA didn’t require tests before CLn hit the stores.
You would think the usual way to proceed with a medical product would be:
1) clinical trial to prove safe and effective
2) manufacturing and marketing
But TopMD scientists recently published the results of a clinical trial for CLn in the journal Pediatric Dermatology, about nine months after I first heard the product was for sale.
Of course dilute bleach baths are a known household treatment to manage skin bacteria. CLn is a portable bleach bath and isn't going to be any more hazardous than what thousands of people are already doing in their bathtubs. But is it any better? Is it worth paying money for?
I think that some marketing analyst decided that doctors around the US were reluctant to buy or recommend CLn because it hadn’t undergone a clinical trial. Now it has—with the shiny label “peer-reviewed,” although the journal it was published in is low-impact, and the “peer” who deemed the study worthy of publication could well have been a single graduate student.
The study might possibly qualify as a “phase 0” trial. It’s conducted on 18 subjects all of whom are given the product. There’s no control group that receives a placebo.
This is a problem, because both the doctors conducting the trial and the patients both want the product to work. So the reported results are bound to look better than they really are. Scientifically, this study is far from the final word on whether CLn is truly effective.
The way to avoid this problem is to have a double-blind randomized control trial where, at the very least, half of the patients get CLn and half get something that looks like it but isn’t, and nobody knows which is which until the results have been recorded.
For an example of how this might be done, at least in a way that looks good from a marketing perspective, you can see that the makers of DermaSilk clothing appear to get it right in their studies, the most recent of which was published online this week.
That the recent CLn study was motivated by marketing is clear from one of its measures. Participants were asked “Would you recommend CLn to a friend?” This is not a data point you see in too many scientific papers.
The company’s press release quotes UC San Diego’s Dr. Larry Eichenfield, chief of pediatric and adolescent dermatology at Children's Hospital, San Diego—a world leader in the field. Eichenfield says “I am excited to read the study by Dr. Ryan et al showing the benefits of TopMD's sodium hypochlorite-based body wash.”
The release doesn’t mention that Eichenfield sits on TopMD’s medical board.
I like the idea of CLn, and I think it’s probably a valuable product. I’m happy they sent me a free bottle to review back in October, and I’m keeping it in case I need it. But I wish they could present some more convincing evidence that it works. Are they afraid that it doesn’t? If not, why not use a control group in the study?
Tuesday, May 21, 2013
Where to look for a surprise eczema cure to emerge
As I wrote in the previous post, the outlook is bleak for new eczema therapies that might qualify as a “cure.” On the fronts of barrier protection and repair and anti-inflammatories, nothing revolutionary is in the works apart from, perhaps, dupilumab, Regeneron’s antibody to IL-4. I can’t see anything emerging from research and entering and successfully exiting clinical trials for at least 25 years.
What might I have left out of this discussion? Where could a surprise come from?
Itch. Itch was the area that occurred to me. Imagine being able to break the itch-scratch cycle in eczema. You know what it’s like: your skin flares up and the itch becomes unbearable. You scratch to get relief. Sometimes you scratch in your sleep. Then your skin is torn up, which for a start can be embarrassing, but also often leads to infection. If there were no itch to begin with, eczema might never become anything more than a minor rash. Its impact on quality of life would be greatly minimized.
I believe we might see a convergence of two major trends that would result in a new anti-itch drug that patients could take in pill or cream form.
The first trend: In the past few years I have seen a number of papers describing newly identified neurons that transmit the sensation of itch, distinct from pain. The experiments were done on animals such as mice and cats; I don’t think these neurons have been found in people yet. But you can bet there are many scientists beavering away to be the first in the field.
Turning on or blocking neural receptors is what drugs do best. Think anesthetics. These itch neurons, if found in humans, are likely going to have receptors similar to those in other animals, and the search will be on to find drugs that block the receptors.
(You could also imagine a therapy using RNA interference to prevent neurons in the skin from making itch receptors in the first place.)
The second trend: scientists are developing powerful new techniques to speed the drug discovery process. While it does take around 15 years to take a new drug all the way through clinical trials to FDA approval, the path is shorter for “repurposed” drugs (such as Viagra, originally planned as a heart medication). The barrier is lower because the drug has already been proven nontoxic. Repurposed drugs have been approved as treatments for one condition but have side effects that, depending on your perspective, qualify as primary effects. There could well be an FDA-approved anti-itch drug out there already. It’s just being used to treat toenail fungus.
A company I am familiar with (I know the founders), SeaChange Pharmaceuticals, developed a rigorous way to search through databases of drugs and identify potential side effects or secondary uses, based on the chemistry of the protein targets for the drugs. (Wired magazine named SeaChange’s technology one of the top 10 breakthroughs of 2009.)
The idea would be that scientists would identify itch neurons in humans, and pin down the itch receptor; then somebody at Pfizer or Novartis or whatever would use a SeaChange-like technique to find FDA-approved drugs that block the receptor. Presto: no more itch. Conceivably this might happen within a decade.
Now, evidently these new drug discovery techniques could be applied in the areas of anti-inflammatories, or barrier repair. I think, though, that itch is a prime candidate for a surprise eczema “cure” because it’s likely that the itch sensation comes down to a single receptor. Blocking that receptor by a conventional drug will be a relatively simple task, compared to controlling inflammation without leaving the patient vulnerable to infection, or taking on the dubious task of compensating for a defective skin barrier in infants.
That’s my opinion.
What might I have left out of this discussion? Where could a surprise come from?
Itch. Itch was the area that occurred to me. Imagine being able to break the itch-scratch cycle in eczema. You know what it’s like: your skin flares up and the itch becomes unbearable. You scratch to get relief. Sometimes you scratch in your sleep. Then your skin is torn up, which for a start can be embarrassing, but also often leads to infection. If there were no itch to begin with, eczema might never become anything more than a minor rash. Its impact on quality of life would be greatly minimized.
I believe we might see a convergence of two major trends that would result in a new anti-itch drug that patients could take in pill or cream form.
The first trend: In the past few years I have seen a number of papers describing newly identified neurons that transmit the sensation of itch, distinct from pain. The experiments were done on animals such as mice and cats; I don’t think these neurons have been found in people yet. But you can bet there are many scientists beavering away to be the first in the field.
Turning on or blocking neural receptors is what drugs do best. Think anesthetics. These itch neurons, if found in humans, are likely going to have receptors similar to those in other animals, and the search will be on to find drugs that block the receptors.
(You could also imagine a therapy using RNA interference to prevent neurons in the skin from making itch receptors in the first place.)
The second trend: scientists are developing powerful new techniques to speed the drug discovery process. While it does take around 15 years to take a new drug all the way through clinical trials to FDA approval, the path is shorter for “repurposed” drugs (such as Viagra, originally planned as a heart medication). The barrier is lower because the drug has already been proven nontoxic. Repurposed drugs have been approved as treatments for one condition but have side effects that, depending on your perspective, qualify as primary effects. There could well be an FDA-approved anti-itch drug out there already. It’s just being used to treat toenail fungus.
A company I am familiar with (I know the founders), SeaChange Pharmaceuticals, developed a rigorous way to search through databases of drugs and identify potential side effects or secondary uses, based on the chemistry of the protein targets for the drugs. (Wired magazine named SeaChange’s technology one of the top 10 breakthroughs of 2009.)
The idea would be that scientists would identify itch neurons in humans, and pin down the itch receptor; then somebody at Pfizer or Novartis or whatever would use a SeaChange-like technique to find FDA-approved drugs that block the receptor. Presto: no more itch. Conceivably this might happen within a decade.
Now, evidently these new drug discovery techniques could be applied in the areas of anti-inflammatories, or barrier repair. I think, though, that itch is a prime candidate for a surprise eczema “cure” because it’s likely that the itch sensation comes down to a single receptor. Blocking that receptor by a conventional drug will be a relatively simple task, compared to controlling inflammation without leaving the patient vulnerable to infection, or taking on the dubious task of compensating for a defective skin barrier in infants.
That’s my opinion.
Saturday, May 18, 2013
Why there will be no cure for eczema for at least 25 years
In a previous post, I made the Eeyore-like prediction that we are unlikely to see a cure for eczema during my lifetime, which means the next 40 years.
Upon reflection, I have become more optimistic: now I only think we might have 25 years to wait.
Several factors combine to make this so: our incomplete understanding of eczema; the ratchet-like course of the disease; its allergic component; and the expense and inertia of drug development.
As currently understood, eczema is initially a defective skin barrier that lets in allergens. In the first few years of life, children develop antibodies that protect them from disease over their lifetime. The defective barrier overstimulates this part of the immune system, and children build the capacity for allergic reactions to common things in the environment that most people don’t react to—pollen and foods for example.
The allergies get locked in. What may originally have been a leaky skin barrier now gets connected to allergies and inflammation.
In recent years scientists have discovered a number of genetic defects in various components of the skin barrier—the super-protein filaggrin, in particular. I can understand that the average patient must have the impression that with this genetic data is coming in, all that scientists have to do is develop targeted drugs to solve the defects. Or gene therapy to replace the bad genes. Surely these are on the horizon?
Here’s why they aren’t. Let’s start with gene therapy. Only one gene therapeutic has been approved anywhere in the world. The European Commission gave permission for Glybera to be used to treat a rare metabolic disease. Gene therapy is most famous in the US for the 1999 death of a teenager who signed up for a risky clinical trial. It is unlikely that over the next few decades we’ll see gene therapies emerge for anything but rare, fatal, incurable diseases. Eczema doesn’t qualify—and even if you could fix the skin barrier by gene therapy, you’d have to act within the first few months of life. What parent would let doctors give their newborn a potentially lethal treatment based only on the likelihood that the kid might grow up to have eczema?
Another possibility is RNA interference, a technique that blocks the conversion of genetic information into protein. RNAi was discovered sometime in the past two decades and recently the FDA approved the very first RNAi therapeutic, for a rare metabolic disease. To treat eczema, RNAi might be used to cut down on the amount of inflammatory molecules produced in the body or in the skin. A number of academic laboratories--I am aware of a couple in Japan--are looking at RNAi for eczema. However, there are no therapies anywhere near a clinical trial, and new "drugs" in this field would face even steeper regulatory hurdles than conventional drugs. Conversely, the reason to get excited about RNAi is that in theory it could allow us to choose which inflammatory molecules to turn off (rather than shutting down most of the immune system, as steroids do).
Now, let's consider traditional drug discovery. Research does show that filaggrin defects are found in up to 50% of patients with severe eczema. (Naturally, there are apparently unaffected people who have filaggrin defects, as well as eczema patients who do not.)
So you’re going to develop some drug to target filaggrin? Irwin McLean, the filaggrin expert, says that targeting filaggrin could have a big payoff. But he admits that little is known about how the filaggrin gene is turned on or off. Eventually we will know, and perhaps that knowledge will suggest what drug might work.
The question is how a drug might fix or compensate for the defect. [See the comments for a couple possibilities.] And if we eventually find a drug that can correct for a single or double filaggrin mutation, there is still the question of how much benefit that will provide if a patient has already developed allergies.
Drugs are just not custom-designed—that is currently a pipe dream. Drug discovery is time-consuming and costly. It takes $1 billion and 15 years of trials to get a drug approved by the FDA. Scientists start with the protein of interest. Then they screen gigantic libraries of drugs to see if any of them affect the protein in useful ways. They tweak those initial “lead” compounds to make them better.
Then they file an application for a new drug. Then they proceed to animal trials: mice, rats, dogs, pigs, chimps. Then human trials—phase 1, 2, 3, 4. At any stage, and if you’re lucky it’s the early going, it can become apparent that your drug is ineffective or toxic.
And here’s another factor: many proteins are just not “druggable” for various reasons. Because of the shape of the molecule or the way it interacts with something else, tiny drug molecules can’t get to the active site; or they get in but can’t get out. Etc.
It is extremely difficult to develop new drugs.
Also, in the past few years the pharmaceutical industry has been in a slow-motion crash. Big companies are laying off scientists because a lot of the original big moneymaking drugs are coming off-patent and not generating enough income for R&D anymore.
Add to this the fact that there’s hardly anything in the pipeline for atopic dermatitis. I know Anacor has two candidates in Phase II trials—new topical anti-inflammatories. Great, but hardly revolutionary. Regeneron has something interesting going: dupilumab, a monoclonal anti-IL4 antibody. It’s in Phase I.
Venture capital won’t even invest in startup companies unless their technology has passed Phase II.
You can understand my pessimism.
Next: why I might be wrong
Upon reflection, I have become more optimistic: now I only think we might have 25 years to wait.
Several factors combine to make this so: our incomplete understanding of eczema; the ratchet-like course of the disease; its allergic component; and the expense and inertia of drug development.
As currently understood, eczema is initially a defective skin barrier that lets in allergens. In the first few years of life, children develop antibodies that protect them from disease over their lifetime. The defective barrier overstimulates this part of the immune system, and children build the capacity for allergic reactions to common things in the environment that most people don’t react to—pollen and foods for example.
The allergies get locked in. What may originally have been a leaky skin barrier now gets connected to allergies and inflammation.
In recent years scientists have discovered a number of genetic defects in various components of the skin barrier—the super-protein filaggrin, in particular. I can understand that the average patient must have the impression that with this genetic data is coming in, all that scientists have to do is develop targeted drugs to solve the defects. Or gene therapy to replace the bad genes. Surely these are on the horizon?
Here’s why they aren’t. Let’s start with gene therapy. Only one gene therapeutic has been approved anywhere in the world. The European Commission gave permission for Glybera to be used to treat a rare metabolic disease. Gene therapy is most famous in the US for the 1999 death of a teenager who signed up for a risky clinical trial. It is unlikely that over the next few decades we’ll see gene therapies emerge for anything but rare, fatal, incurable diseases. Eczema doesn’t qualify—and even if you could fix the skin barrier by gene therapy, you’d have to act within the first few months of life. What parent would let doctors give their newborn a potentially lethal treatment based only on the likelihood that the kid might grow up to have eczema?
Another possibility is RNA interference, a technique that blocks the conversion of genetic information into protein. RNAi was discovered sometime in the past two decades and recently the FDA approved the very first RNAi therapeutic, for a rare metabolic disease. To treat eczema, RNAi might be used to cut down on the amount of inflammatory molecules produced in the body or in the skin. A number of academic laboratories--I am aware of a couple in Japan--are looking at RNAi for eczema. However, there are no therapies anywhere near a clinical trial, and new "drugs" in this field would face even steeper regulatory hurdles than conventional drugs. Conversely, the reason to get excited about RNAi is that in theory it could allow us to choose which inflammatory molecules to turn off (rather than shutting down most of the immune system, as steroids do).
Now, let's consider traditional drug discovery. Research does show that filaggrin defects are found in up to 50% of patients with severe eczema. (Naturally, there are apparently unaffected people who have filaggrin defects, as well as eczema patients who do not.)
So you’re going to develop some drug to target filaggrin? Irwin McLean, the filaggrin expert, says that targeting filaggrin could have a big payoff. But he admits that little is known about how the filaggrin gene is turned on or off. Eventually we will know, and perhaps that knowledge will suggest what drug might work.
The question is how a drug might fix or compensate for the defect. [See the comments for a couple possibilities.] And if we eventually find a drug that can correct for a single or double filaggrin mutation, there is still the question of how much benefit that will provide if a patient has already developed allergies.
Drugs are just not custom-designed—that is currently a pipe dream. Drug discovery is time-consuming and costly. It takes $1 billion and 15 years of trials to get a drug approved by the FDA. Scientists start with the protein of interest. Then they screen gigantic libraries of drugs to see if any of them affect the protein in useful ways. They tweak those initial “lead” compounds to make them better.
Then they file an application for a new drug. Then they proceed to animal trials: mice, rats, dogs, pigs, chimps. Then human trials—phase 1, 2, 3, 4. At any stage, and if you’re lucky it’s the early going, it can become apparent that your drug is ineffective or toxic.
And here’s another factor: many proteins are just not “druggable” for various reasons. Because of the shape of the molecule or the way it interacts with something else, tiny drug molecules can’t get to the active site; or they get in but can’t get out. Etc.
It is extremely difficult to develop new drugs.
Also, in the past few years the pharmaceutical industry has been in a slow-motion crash. Big companies are laying off scientists because a lot of the original big moneymaking drugs are coming off-patent and not generating enough income for R&D anymore.
Add to this the fact that there’s hardly anything in the pipeline for atopic dermatitis. I know Anacor has two candidates in Phase II trials—new topical anti-inflammatories. Great, but hardly revolutionary. Regeneron has something interesting going: dupilumab, a monoclonal anti-IL4 antibody. It’s in Phase I.
Venture capital won’t even invest in startup companies unless their technology has passed Phase II.
You can understand my pessimism.
Next: why I might be wrong
Wednesday, May 15, 2013
What would count as a "cure" for eczema?
A commenter on my most recent post took me to task for being too pessimistic about the possibility of a cure for eczema appearing in my lifetime. (For the record, I’m 41, so that means within the next 40 years.)
This raises a good question: what qualifies as a "cure"? And who cares?
You know if you care. You're an adult who lives with severe eczema, or the parent of a severely affected child.
I propose that a cure be defined as a therapy that doesn’t take that long to apply and relieves the symptoms to less than a quarter of what they were to begin with. (Take your pick of how to measure it; how about SCORAD?)
A cure would take less than 10 minutes out of your day, and you could wear a swimsuit to the beach.
Most likely a cure would take the form of a drug or biotherapy (e.g. antibody) administered as a pill, cream, or injection. It would be OK if the cure took a whole day to administer, as long as you only had to do it once a year. That would work out to about 10 minutes per day.
Intense, complicated therapy like the National Jewish Health regimen—moisturizing, wet wraps, special diet, and a team dedicated to your personal health, may work for a small number of people for a limited time, but is too expensive and impractical to count as a cure.
What about "partial" cures? Eczema is a complex disease with many aspects that affect each other: skin barrier, allergies, itch, psychology. What if we discover an agent that relieves allergies or turns off itch? Would that count as a cure?
I think it would—if it took a patient less than 10 minutes a day to apply, and they could wear a swimsuit to the beach.
In following posts, I will explore why such a cure will likely NOT happen within the next 40 years—and then I will explain why it COULD happen in the next 40 years.
This raises a good question: what qualifies as a "cure"? And who cares?
You know if you care. You're an adult who lives with severe eczema, or the parent of a severely affected child.
I propose that a cure be defined as a therapy that doesn’t take that long to apply and relieves the symptoms to less than a quarter of what they were to begin with. (Take your pick of how to measure it; how about SCORAD?)
A cure would take less than 10 minutes out of your day, and you could wear a swimsuit to the beach.
Most likely a cure would take the form of a drug or biotherapy (e.g. antibody) administered as a pill, cream, or injection. It would be OK if the cure took a whole day to administer, as long as you only had to do it once a year. That would work out to about 10 minutes per day.
Intense, complicated therapy like the National Jewish Health regimen—moisturizing, wet wraps, special diet, and a team dedicated to your personal health, may work for a small number of people for a limited time, but is too expensive and impractical to count as a cure.
What about "partial" cures? Eczema is a complex disease with many aspects that affect each other: skin barrier, allergies, itch, psychology. What if we discover an agent that relieves allergies or turns off itch? Would that count as a cure?
I think it would—if it took a patient less than 10 minutes a day to apply, and they could wear a swimsuit to the beach.
In following posts, I will explore why such a cure will likely NOT happen within the next 40 years—and then I will explain why it COULD happen in the next 40 years.
Monday, May 13, 2013
June 8 Itching for a Cure walk in New Jersey: it's not about you
The National Eczema Association recently announced the second annual Itching for a Cure walk, which will raise awareness and funds for eczema outreach and research. It will take place June 8 on the Monmouth University campus in New Jersey--essentially greater New York City. (Last year's walk was held in Asheville, North Carolina.)
The largest barrier for me, as an adult patient, to participating in such a walk--were one to be held in the area I live in--is embarrassment. Eczema is not a socially acceptable disease. It's there on your skin, sometimes your face, where people can see there's something wrong with you. And when it's not visible, that's a good thing. You want to hide it.
In this matter, there's a huge difference between a parent of a child with eczema and an adult patient with eczema. The mother or father of a child with eczema is not embarrassed. They are concerned and want to do everything they can to make their child better.
On top of the embarrassment factor, it seems a bit selfish, a bit like a panhandler, for an adult patient to take part in an eczema walk. Sponsor me, it seems to say, to raise money for a cure for me!
Mothers and fathers are ready to fight for their kids. They are not doing it for themselves. They will proudly take part in an eczema walk, and look you in the eye.
The absence of adult patients from Itching for a Cure is probably not a major factor. After all, eczema is predominantly a condition that children outgrow. But how might we convince adult patients, including me, to take part?
I think the key lies in altruism. It's not about you.
Let's face it--if you're raising money to increase awareness of the prevalence of eczema, or how it should be properly treated, or to fund research that might lead to a pharmaceutical cure--you are not doing it for yourself. There will be no cure for eczema in your lifetime. You are doing it for other people. Your grandkids, and millions of people you will never know.
It becomes a lot less embarrassing when you're doing it for somebody else.
And that is why if there is ever an Itching for a Cure walk in my area, I'll be signing up. I know exactly how shitty it is to live with this condition, and how important it is that other people be spared the torment and the embarrassment. It's not me I'll be doing it for--it's you!
The largest barrier for me, as an adult patient, to participating in such a walk--were one to be held in the area I live in--is embarrassment. Eczema is not a socially acceptable disease. It's there on your skin, sometimes your face, where people can see there's something wrong with you. And when it's not visible, that's a good thing. You want to hide it.
In this matter, there's a huge difference between a parent of a child with eczema and an adult patient with eczema. The mother or father of a child with eczema is not embarrassed. They are concerned and want to do everything they can to make their child better.
On top of the embarrassment factor, it seems a bit selfish, a bit like a panhandler, for an adult patient to take part in an eczema walk. Sponsor me, it seems to say, to raise money for a cure for me!
Mothers and fathers are ready to fight for their kids. They are not doing it for themselves. They will proudly take part in an eczema walk, and look you in the eye.
The absence of adult patients from Itching for a Cure is probably not a major factor. After all, eczema is predominantly a condition that children outgrow. But how might we convince adult patients, including me, to take part?
I think the key lies in altruism. It's not about you.
Let's face it--if you're raising money to increase awareness of the prevalence of eczema, or how it should be properly treated, or to fund research that might lead to a pharmaceutical cure--you are not doing it for yourself. There will be no cure for eczema in your lifetime. You are doing it for other people. Your grandkids, and millions of people you will never know.
It becomes a lot less embarrassing when you're doing it for somebody else.
And that is why if there is ever an Itching for a Cure walk in my area, I'll be signing up. I know exactly how shitty it is to live with this condition, and how important it is that other people be spared the torment and the embarrassment. It's not me I'll be doing it for--it's you!
Thursday, May 9, 2013
Thumbs up for shea butter as a scalp moisturizer
In my ongoing search for a scalp moisturizer, I have a new favorite: shea butter.
I had heard about shea butter about for years. I hadn't tried it because it cost a lot and seemed a kooky natural product of dubious merit and uncertain quality control. But dry skin and eczema on my scalp is now my primary problem. For several months I have been coating my head with Aveeno Daily Moisturizing lotion and feeling like I'm wearing a rubber bathing cap all day. It works OK but leaves something to be desired as a hair product. So I was up for trying new things.
Then, I found a jar of shea butter just sitting around on my four-year-old daughter's dresser. She has eczema and my wife must have bought the shea butter and tried it out without me knowing. (Cue the eye-rolling on my wife's part.) Anyway, the stuff was no longer in use, she informed me, so, having already paid for it, I was free to try it out.
The brand was True Blue Spa Too Shea, if you're interested. $17.50 for 3.5 oz.
It goes on like actual butter--it's hard at first, but you take a bit in your fingers and it warms up and melts a bit. Then you rub it on your scalp and once it's on, it stays melted.
It works for me because I buzz my head with a 1/2 inch clipper attachment. So I am not wasting too much of it on my actual hair.
The feeling is a little greasy but not terrible. Plus shea butter is actually used as a hair product. Would you believe I had a compliment on my hair earlier this week? The first in a very long time.
I looked into shea butter. It comes from the nuts of the shea tree in west and central Africa. It's a complex fat and apparently there is a wide range in quality. Someone named Samuel Hunter recently created the American Shea Butter Institute, which could well be a one-man operation for all I could determine, to certify various grades of shea butter depending on their oil content, melting profile, impurities and "rancidity values." Shea butter is edible, and therefore goes bad like real butter. (But no mention is made of refrigeration.)
I can't recommend one type or brand of shea butter to use, because it's not clear what would make one better than another. You just wouldn't want it to be rancid, evidently.
I don't search out natural products, because I don't think they're necessarily any better than manufactured moisturizers and so on, but shea butter is the best solution I've found so far for moisturizing my scalp.
I had heard about shea butter about for years. I hadn't tried it because it cost a lot and seemed a kooky natural product of dubious merit and uncertain quality control. But dry skin and eczema on my scalp is now my primary problem. For several months I have been coating my head with Aveeno Daily Moisturizing lotion and feeling like I'm wearing a rubber bathing cap all day. It works OK but leaves something to be desired as a hair product. So I was up for trying new things.
Then, I found a jar of shea butter just sitting around on my four-year-old daughter's dresser. She has eczema and my wife must have bought the shea butter and tried it out without me knowing. (Cue the eye-rolling on my wife's part.) Anyway, the stuff was no longer in use, she informed me, so, having already paid for it, I was free to try it out.
The brand was True Blue Spa Too Shea, if you're interested. $17.50 for 3.5 oz.
It goes on like actual butter--it's hard at first, but you take a bit in your fingers and it warms up and melts a bit. Then you rub it on your scalp and once it's on, it stays melted.
It works for me because I buzz my head with a 1/2 inch clipper attachment. So I am not wasting too much of it on my actual hair.
The feeling is a little greasy but not terrible. Plus shea butter is actually used as a hair product. Would you believe I had a compliment on my hair earlier this week? The first in a very long time.
I looked into shea butter. It comes from the nuts of the shea tree in west and central Africa. It's a complex fat and apparently there is a wide range in quality. Someone named Samuel Hunter recently created the American Shea Butter Institute, which could well be a one-man operation for all I could determine, to certify various grades of shea butter depending on their oil content, melting profile, impurities and "rancidity values." Shea butter is edible, and therefore goes bad like real butter. (But no mention is made of refrigeration.)
I can't recommend one type or brand of shea butter to use, because it's not clear what would make one better than another. You just wouldn't want it to be rancid, evidently.
I don't search out natural products, because I don't think they're necessarily any better than manufactured moisturizers and so on, but shea butter is the best solution I've found so far for moisturizing my scalp.
Tuesday, May 7, 2013
New NEA blog post. Why is the East Coast missing from the Eczema Map Project?
Check out my latest post on the blog of the National Eczema Association. I write about the Eczema Map Project and, in particular, what it's already taught me: that either I have a lot to learn, or there's not much happening on the east coast of the United States, which has traditionally been the power center for academia, industry, and medicine. Why is that?
Thursday, May 2, 2013
The Eczema Map Project: the big picture
Something I've wanted to do for a long time is create a world map of all the major centers or points of interest for eczema patients, doctors and scientists.
Why? Because I feel that we're all largely isolated, even in the internet age. Especially with a disease that makes you want to stay away from other people. We can get on our computers and search for blogs or advice or therapies, but there's very little sense of belonging to a greater community. We don't know what's going on in the big picture.
And so I would like to introduce to you the Eczema Map Project, a work in progress. It is a map of the world marking the locations of key researchers, therapy centers, and patient associations.
I've decided to make the map a permanent tab on this blog, so I can update it continually when I learn about new people or developments.
The items on this map are those that I consider significant--game-changers, not just good dermatologists. But please feel free to write a comment about your dermatologist if you think he or she is above average!
You can see that at present the map is a bit USA and UK-centric. This could be for a few reasons. I largely operate in English, and I live in California, so I tend to hear about developments in the USA more than anywhere else. But it is true that the USA is a very large and well-developed country with some of the best medical care in the world (for those who can afford it--an issue I have strong opinions on, but which I am not going to get into right now). So it may turn out that more of the most important sites are indeed here.
But please tell me what is missing from this map. Is there a major therapy center or a patient association I don't know about? Leading scientists not there? Tell me, and I'll add them. Or, if you think an item doesn't merit being listed, let me know. Nothing is set in stone.
And have fun exploring the world map from an eczema perspective.
View The Eczema Map Project in a full screen map
Why? Because I feel that we're all largely isolated, even in the internet age. Especially with a disease that makes you want to stay away from other people. We can get on our computers and search for blogs or advice or therapies, but there's very little sense of belonging to a greater community. We don't know what's going on in the big picture.
And so I would like to introduce to you the Eczema Map Project, a work in progress. It is a map of the world marking the locations of key researchers, therapy centers, and patient associations.
I've decided to make the map a permanent tab on this blog, so I can update it continually when I learn about new people or developments.
The items on this map are those that I consider significant--game-changers, not just good dermatologists. But please feel free to write a comment about your dermatologist if you think he or she is above average!
You can see that at present the map is a bit USA and UK-centric. This could be for a few reasons. I largely operate in English, and I live in California, so I tend to hear about developments in the USA more than anywhere else. But it is true that the USA is a very large and well-developed country with some of the best medical care in the world (for those who can afford it--an issue I have strong opinions on, but which I am not going to get into right now). So it may turn out that more of the most important sites are indeed here.
But please tell me what is missing from this map. Is there a major therapy center or a patient association I don't know about? Leading scientists not there? Tell me, and I'll add them. Or, if you think an item doesn't merit being listed, let me know. Nothing is set in stone.
And have fun exploring the world map from an eczema perspective.
View The Eczema Map Project in a full screen map
Wednesday, May 1, 2013
Anomalies in the immune system of patients who have experienced eczema herpeticum
Scientists have discovered that eczema patients who have suffered an outbreak of eczema herpeticum possess a subset of T cells that appear to be less effective at fighting viruses than T cells in the rest of the population. The results, published online in the British Journal of Dermatology, may point to an impaired arm of the immune system, a weakness that enables the herpes simplex virus (HSV), the agent of eczema herpeticum, to thrive.
Eczema herpeticum (EH) is a nasty skin infection caused by the HSV. The researchers, led by Donald Leung at National Jewish Health in Denver, took T cells (specifically, the class of T cells that fights viral infection) from 24 eczema patients who had experienced EH. The scientists analyzed various aspects of the T cells, comparing them to T cells taken from control patients—with and without eczema—who had not been infected by HSV. The scientists found that T cells from the EH group were producing less of a signaling molecule called “interferon-gamma” than those from the control groups.
Interferon-gamma is known to play many important roles in the immune response, especially in fighting viral infections.
The researchers also tested the DNA of the patients and found that the EH group were statistically more likely to possess copies of genes encoding “HLA B7” proteins, which hold chopped-up viral fragments on the cell membrane as markers so that T cells can identify and destroy infected cells.
It seems clear to me that a lack of interferon-gamma might be a liability against viruses. (I wouldn't expect this deficiency to be an effect of EH infection rather than a contributing cause, but the authors don't discuss the possibility.)
Owning a copy of HLA B7 might seem to improve your ability to fight infection--especially since that group of proteins have been shown to present fragments of vaccinia virus. However, as Leung pointed out to me in an email, having HLA B7 didn't prevent many of the patients in this study from getting eczema herpeticum.
These results don't have any immediate application to helping patients, but the area they highlight might prove important in protecting patients from eczema herpeticum in the future.
This is the first paper I have seen that acknowledges funding by the Atopic Dermatitis Research Network. I am sure there are many more papers out there, but this is the first I have noticed since the inception of the $31 million program, founded in 2010 to explore skin infections related to eczema.
Eczema herpeticum (EH) is a nasty skin infection caused by the HSV. The researchers, led by Donald Leung at National Jewish Health in Denver, took T cells (specifically, the class of T cells that fights viral infection) from 24 eczema patients who had experienced EH. The scientists analyzed various aspects of the T cells, comparing them to T cells taken from control patients—with and without eczema—who had not been infected by HSV. The scientists found that T cells from the EH group were producing less of a signaling molecule called “interferon-gamma” than those from the control groups.
Interferon-gamma is known to play many important roles in the immune response, especially in fighting viral infections.
The researchers also tested the DNA of the patients and found that the EH group were statistically more likely to possess copies of genes encoding “HLA B7” proteins, which hold chopped-up viral fragments on the cell membrane as markers so that T cells can identify and destroy infected cells.
It seems clear to me that a lack of interferon-gamma might be a liability against viruses. (I wouldn't expect this deficiency to be an effect of EH infection rather than a contributing cause, but the authors don't discuss the possibility.)
Owning a copy of HLA B7 might seem to improve your ability to fight infection--especially since that group of proteins have been shown to present fragments of vaccinia virus. However, as Leung pointed out to me in an email, having HLA B7 didn't prevent many of the patients in this study from getting eczema herpeticum.
These results don't have any immediate application to helping patients, but the area they highlight might prove important in protecting patients from eczema herpeticum in the future.
This is the first paper I have seen that acknowledges funding by the Atopic Dermatitis Research Network. I am sure there are many more papers out there, but this is the first I have noticed since the inception of the $31 million program, founded in 2010 to explore skin infections related to eczema.
Tuesday, April 30, 2013
Evening primrose oil bites the dust as an eczema therapy
An extensive review study of the scientific literature has concluded that swallowing capsules of evening primose oil and borage oil will not relieve your eczema symptoms.
Evening primrose oil and borage oil are "gamma-linoleic acids," or long-chain fatty acids that have a kink in the sixth bond in the chain. They are also called omega-6 fatty acids and have long been touted as beneficial in reducing inflammation and treating autoimmune diseases when taken in capsule form.
A team led by Joel Bamford at the University of Minnesota Medical School read through 27 academic studies, in which 1596 patients had taken part, and concluded that taking evening primrose oil or borage oil had provided no benefit.
I've taken evening primrose oil capsules myself. They were expensive and did nothing for me.
This review seems like it could be the final word on the issue. However, the overall total number of participants is quite low--each study would have had around 50 participants. So it's possible that the authors of this review have just combined a whole lot of garbage results and the overall conclusion is not solid...but if there were some kind of real beneficial effect you'd think a review of this size would detect it.
I'm skeptical of supplements in general. In my experience, eczema is a condition in which diet is indeed important--but the importance lies in leaving out foods that can trigger allergy or inflammation, rather than in consuming certain foods and expecting them to make your skin better.
Evening primrose oil and borage oil are "gamma-linoleic acids," or long-chain fatty acids that have a kink in the sixth bond in the chain. They are also called omega-6 fatty acids and have long been touted as beneficial in reducing inflammation and treating autoimmune diseases when taken in capsule form.
A team led by Joel Bamford at the University of Minnesota Medical School read through 27 academic studies, in which 1596 patients had taken part, and concluded that taking evening primrose oil or borage oil had provided no benefit.
I've taken evening primrose oil capsules myself. They were expensive and did nothing for me.
This review seems like it could be the final word on the issue. However, the overall total number of participants is quite low--each study would have had around 50 participants. So it's possible that the authors of this review have just combined a whole lot of garbage results and the overall conclusion is not solid...but if there were some kind of real beneficial effect you'd think a review of this size would detect it.
I'm skeptical of supplements in general. In my experience, eczema is a condition in which diet is indeed important--but the importance lies in leaving out foods that can trigger allergy or inflammation, rather than in consuming certain foods and expecting them to make your skin better.
Thursday, April 25, 2013
The "Eczema App." Neat, useful, but a heavy advertising touch
I have an iPhone but I’m not crazy about apps. You won’t find me playing Angry Birds or one of those flashy bloop-de-bloop games during my commute. I’ve figured out how to listen to audiobooks and that’s good enough for me.
Still, I was intrigued when I saw the National Eczema Association had developed a free “Eczema App” together with pharma giant Bayer. I decided to check it out. It took seconds to download from the App Store to my iPhone 5.
The Eczema App is three things at the same time: a flare tracker and reporter; an information reference; and an advertisement for Bayer’s topical steroid Desonate.
The flare tracker and reporter seems like it could be pretty useful, especially to a parent trying to figure out what is triggering his or her child’s eczema. The app lets you register when a flare starts and stops. In between, you can note what you think might be triggering it, and take pictures of the damage. You can email a flare report, images and notes included, to your doctor or nurse.
And you can set up profiles for as many as five people—I set up one for myself and one for my daughter.
My only quibble with this section was that I had trouble finding the button that would let me report that my flare had ended. (This function is hidden in the Tracker > Update > Flare-up details tab.)
The second, the info-and-news section, is a nice little package of basic facts and advice for patients with eczema or parents of affected children. It’s pitched toward someone who hasn’t encountered eczema before. Me, I’ve had it for 41 years and I blog about it, so my first reaction was that this section was too dumbed-down, but I can see that it could be useful to a newbie.
I do wish the info section didn’t mention antihistamines though. They do not help prevent the itch of eczema and their only utility is that they can make you drowsy and might make it easier for you to go to sleep.
The Desonate advertising section is placed toward the bottom of the app. It is semi-discreet. But it still seems like pushy pharma marketing to me. I hope the NEA got some decent sponsorship funds in return for the exposure.
My overall impression of the app was colored by the advertising. It's great that you can use your iPhone to collect and report medical data. But the app is much like a free mug or pen you might pick up at a convention. You drink your coffee or scribble your notes, and it gets the job done, but that logo is always staring at you from your desk.
When I tweeted about the Eczema App, I heard back on Twitter from Emma Williams, a nurse in Swansea, Wales who operates a specialty eczema clinic. She too has an eczema app, "Eczema Expert." I took a glance at it in the App Store but was put off by a couple glaring mistakes—one of the questions in the diagnostic section was “Do you itchy skin?” and there was a mention of “tropical” steroids. I couldn’t bring myself to spend $1.99 because the typos gave a shoddy impression. Let me know when you’ve fixed the app, Emma!
Still, I was intrigued when I saw the National Eczema Association had developed a free “Eczema App” together with pharma giant Bayer. I decided to check it out. It took seconds to download from the App Store to my iPhone 5.
The Eczema App is three things at the same time: a flare tracker and reporter; an information reference; and an advertisement for Bayer’s topical steroid Desonate.
The flare tracker and reporter seems like it could be pretty useful, especially to a parent trying to figure out what is triggering his or her child’s eczema. The app lets you register when a flare starts and stops. In between, you can note what you think might be triggering it, and take pictures of the damage. You can email a flare report, images and notes included, to your doctor or nurse.
And you can set up profiles for as many as five people—I set up one for myself and one for my daughter.
My only quibble with this section was that I had trouble finding the button that would let me report that my flare had ended. (This function is hidden in the Tracker > Update > Flare-up details tab.)
The second, the info-and-news section, is a nice little package of basic facts and advice for patients with eczema or parents of affected children. It’s pitched toward someone who hasn’t encountered eczema before. Me, I’ve had it for 41 years and I blog about it, so my first reaction was that this section was too dumbed-down, but I can see that it could be useful to a newbie.
I do wish the info section didn’t mention antihistamines though. They do not help prevent the itch of eczema and their only utility is that they can make you drowsy and might make it easier for you to go to sleep.
The Desonate advertising section is placed toward the bottom of the app. It is semi-discreet. But it still seems like pushy pharma marketing to me. I hope the NEA got some decent sponsorship funds in return for the exposure.
My overall impression of the app was colored by the advertising. It's great that you can use your iPhone to collect and report medical data. But the app is much like a free mug or pen you might pick up at a convention. You drink your coffee or scribble your notes, and it gets the job done, but that logo is always staring at you from your desk.
***
When I tweeted about the Eczema App, I heard back on Twitter from Emma Williams, a nurse in Swansea, Wales who operates a specialty eczema clinic. She too has an eczema app, "Eczema Expert." I took a glance at it in the App Store but was put off by a couple glaring mistakes—one of the questions in the diagnostic section was “Do you itchy skin?” and there was a mention of “tropical” steroids. I couldn’t bring myself to spend $1.99 because the typos gave a shoddy impression. Let me know when you’ve fixed the app, Emma!
Wednesday, April 24, 2013
New type of white blood cell identified; may play role in eczema
Scientists have identified a new type of white blood cell found in the upper layers of the skin that can either trigger or shut down inflammation.
The research was carried out in mice, which are commonly used as models for the human immune system. There is no proof that the same cells exist in humans, but these results will certainly impel researchers to look for them. It is possible that the newly identified cells play a role in eczema.
The cell type, “group 2 innate lymphoid cells” (ILC2), protects mice against parasitic worms called helminths. In mice, the cells appear to be the main source of the signaling molecule IL-13, known to be important in type 2 immunity—the arm of the immune system that is over-active in allergic disease and eczema.
The scientists took video that showed ILC2 cells moving around in the skin and occasionally stopping to make physical contact with mast cells. Mast cells play an important role in the early stages of inflammation. They are suppressed by IL-13.
However, the researchers also introduced ILC2 cells into mice that had no B or T cells (the white blood cells responsible for much of the immune response). In these mice, stimulating ILC2 cells caused inflammation with symptoms that looked like eczema.
So it appears that ILC2 cells can increase or decrease inflammation, depending on the signaling molecules they secrete. Potentially, drugs might be discovered to control ILC2 cells in the skin and, through them, manage eczema.
The research was performed by a joint Australian/New Zealand/American team led by Wolfgang Weninger, a professor of dermatology at the University of Sydney. It was published in the journal Nature Immunology.
The research was carried out in mice, which are commonly used as models for the human immune system. There is no proof that the same cells exist in humans, but these results will certainly impel researchers to look for them. It is possible that the newly identified cells play a role in eczema.
The cell type, “group 2 innate lymphoid cells” (ILC2), protects mice against parasitic worms called helminths. In mice, the cells appear to be the main source of the signaling molecule IL-13, known to be important in type 2 immunity—the arm of the immune system that is over-active in allergic disease and eczema.
The scientists took video that showed ILC2 cells moving around in the skin and occasionally stopping to make physical contact with mast cells. Mast cells play an important role in the early stages of inflammation. They are suppressed by IL-13.
However, the researchers also introduced ILC2 cells into mice that had no B or T cells (the white blood cells responsible for much of the immune response). In these mice, stimulating ILC2 cells caused inflammation with symptoms that looked like eczema.
So it appears that ILC2 cells can increase or decrease inflammation, depending on the signaling molecules they secrete. Potentially, drugs might be discovered to control ILC2 cells in the skin and, through them, manage eczema.
The research was performed by a joint Australian/New Zealand/American team led by Wolfgang Weninger, a professor of dermatology at the University of Sydney. It was published in the journal Nature Immunology.
Tuesday, April 23, 2013
Scalp eczema therapy: a work in progress
Last year I wrote about scalp eczema. The post is one of the most-read on this blog. Good news: I’m going to write about it again! The reason: once again, scalp eczema is a problem for me.
My scalp trouble seems to follow a yearly cycle, and it might have something to do with pollen, since I had it last spring. Or it might be just that I started swimming again a few months ago. There’s no getting around the fact that swimming is bad for my skin. (I swim, nevertheless, because it’s good for my back.)
I just get this ridiculously dry scalp that starts breaking out into itchy patches. It is extremely hard not to pick at and scratch.
It seems to be a three-part problem: inflammation, dryness, and bad habit.
To treat the inflammation I rub in steroid, which is bad because 1) it’s quite strong (fluocinonide ointment) and 2) it hardly works at all.
I also use a tar shampoo, T-Gel. I love tar shampoo—it’s got a great bite to it and knocks the itch out for a few hours. But it’s a shampoo, made from detergents, which wash oils out and leave my scalp screaming dry.
I realized that the tar shampoo was part of the problem, so now I use it only once a week.
I used to follow tar shampoo with jojoba oil. Jojoba is an expensive, fine-grade natural oil that comes from the seeds of a Mexican desert plant. It is my conclusion that jojoba is a waste of time and money. It doesn't do much besides run down behind your ears and make your neck greasy.
Now I follow my tar shampoo with Aveeno Daily Moisturizing lotion. That's right, I rub it all over my head. It dries to a shellac and makes me look like my grandfather when he used Brylcreem back in the 1950s. Aveeno is good both because it contains soothing oatmeal extract and dimethicone, a rubbery polymer that holds moisture well.
This is not a perfect solution, and a bit disgusting. But it’s better than rubbing in strong steroid ointment out of desperation, I think.
In order to use the Aveeno lotion (to get more of it on my scalp and less on my hair), I buzz my hair short. I’ve got a home barber kit for this. I use the 0.5” or 0.75” attachments. I gave myself a haircut last week, after waiting several months for my scalp eczema to go away so I could go to the barber.
I’m not super-keen on Aveeno for this though. I am going to try shea butter, which at least has the virtue of being a bona fide hair product.
I am surprised that very few commercial companies, if any, make moisturizing scalp lotion. You’d think there would be a market for it. Cosmetics companies seem to approach this as a conditioner problem, as if we’re all worried about how beautiful and manageable our hair is. Well I’m not. I’m a 41-year-old balding man and I have no use for conditioner.
Ironically, Kamedis, the Chinese herbal therapeutics company whose skin lotion I reviewed recently (and none too positively) makes scalp lotion for eczema. Maybe I should give that a shot!
Let’s not forget that my bad habit of picking at dry skin and scabs on my scalp is part of the problem too. I know that it’s possible to quit the habit to some degree by undergoing habit-reversal training.
There are two phases to habit reversal. In the first, you count how many times you touch, pick, or scratch yourself during the day. In the second, you train yourself to recognize that you're about to scratch, and to resist the urge, either by clenching your hand or digging your nails into your palm.
Here’s the barrier that prevents me from self-training—I don’t own a simple digital counter that would enable me to keep track of how many times I am scratching. Last time I tried habit-reversal, I made pencil marks on the back of a business card. I touch my head more than 500 times a day, apparently. It's a pain to have to keep making pencil marks.
I just looked on Amazon. This is what I want. Isn’t it ridiculous that I am not able to stop picking at my scalp because I don’t have a little clicker device that costs less than $7.00? I just bought it.
My scalp trouble seems to follow a yearly cycle, and it might have something to do with pollen, since I had it last spring. Or it might be just that I started swimming again a few months ago. There’s no getting around the fact that swimming is bad for my skin. (I swim, nevertheless, because it’s good for my back.)
I just get this ridiculously dry scalp that starts breaking out into itchy patches. It is extremely hard not to pick at and scratch.
It seems to be a three-part problem: inflammation, dryness, and bad habit.
To treat the inflammation I rub in steroid, which is bad because 1) it’s quite strong (fluocinonide ointment) and 2) it hardly works at all.
I also use a tar shampoo, T-Gel. I love tar shampoo—it’s got a great bite to it and knocks the itch out for a few hours. But it’s a shampoo, made from detergents, which wash oils out and leave my scalp screaming dry.
I realized that the tar shampoo was part of the problem, so now I use it only once a week.
I used to follow tar shampoo with jojoba oil. Jojoba is an expensive, fine-grade natural oil that comes from the seeds of a Mexican desert plant. It is my conclusion that jojoba is a waste of time and money. It doesn't do much besides run down behind your ears and make your neck greasy.
Now I follow my tar shampoo with Aveeno Daily Moisturizing lotion. That's right, I rub it all over my head. It dries to a shellac and makes me look like my grandfather when he used Brylcreem back in the 1950s. Aveeno is good both because it contains soothing oatmeal extract and dimethicone, a rubbery polymer that holds moisture well.
This is not a perfect solution, and a bit disgusting. But it’s better than rubbing in strong steroid ointment out of desperation, I think.
In order to use the Aveeno lotion (to get more of it on my scalp and less on my hair), I buzz my hair short. I’ve got a home barber kit for this. I use the 0.5” or 0.75” attachments. I gave myself a haircut last week, after waiting several months for my scalp eczema to go away so I could go to the barber.
I’m not super-keen on Aveeno for this though. I am going to try shea butter, which at least has the virtue of being a bona fide hair product.
I am surprised that very few commercial companies, if any, make moisturizing scalp lotion. You’d think there would be a market for it. Cosmetics companies seem to approach this as a conditioner problem, as if we’re all worried about how beautiful and manageable our hair is. Well I’m not. I’m a 41-year-old balding man and I have no use for conditioner.
Ironically, Kamedis, the Chinese herbal therapeutics company whose skin lotion I reviewed recently (and none too positively) makes scalp lotion for eczema. Maybe I should give that a shot!
* * *
Let’s not forget that my bad habit of picking at dry skin and scabs on my scalp is part of the problem too. I know that it’s possible to quit the habit to some degree by undergoing habit-reversal training.
There are two phases to habit reversal. In the first, you count how many times you touch, pick, or scratch yourself during the day. In the second, you train yourself to recognize that you're about to scratch, and to resist the urge, either by clenching your hand or digging your nails into your palm.
Here’s the barrier that prevents me from self-training—I don’t own a simple digital counter that would enable me to keep track of how many times I am scratching. Last time I tried habit-reversal, I made pencil marks on the back of a business card. I touch my head more than 500 times a day, apparently. It's a pain to have to keep making pencil marks.
I just looked on Amazon. This is what I want. Isn’t it ridiculous that I am not able to stop picking at my scalp because I don’t have a little clicker device that costs less than $7.00? I just bought it.
Thursday, April 18, 2013
Eczema product review: TOPICMedis Calming Lotion (traditional Chinese herbal)
My take on traditional Chinese medicine (TCM), of the herbal variety, is that the theory is bullshit. Yin/yang? The "five elements" being wood, fire, earth, metal, and water? "Energy meridians"? Medieval thinking.
Herbal medicine, though, is a major foundation of modern pharmacy. TCM herbs contain molecules that are biologically active--what Western medicine would call drugs.
This is why I doubt that the TCM practice of dosing with several (sometimes nine or ten) herbs in combination is a good idea. The potential for side effects and drug interactions is too high.
I acknowledge that empirical, practical knowledge is a powerful way to solve problems, and that TCM could work for certain conditions in the right circumstances. You would need to have a very experienced TCM practitioner treating a patient for a condition that the expert was familiar with. You could get results--even though the theory is bunk.
But I am skeptical when companies market TCM herb-containing products directly to consumers. The treatment can't be tailored to the patient. The dosing and quality control are dubious. How do you know what the active ingredients are, and are they consistent from batch to batch?
And most importantly, who has verified that these things work and aren't toxic?
The answer is: nobody.
Recently I was asked whether I would review TOPICMedis Calming Lotion, a product of the Israeli company Kamedis. The lotion contains four TCM herbal extracts. I was intrigued, and agreed--because I wanted to learn which TCM herbs might be useful in treating eczema.
So what's in TOPICMedis Calming Lotion?
The first three ingredients listed are "water, glycerin, dimethicone & cyclotetrasiloxane & polysilicone-11."
I like dimethicone. It's a rubbery polymer that Aveeno includes in their Daily Moisturizing Lotion and I find it seals moisture into my skin. Not exactly a traditional herb though.
The lotion contains extracts from four herbs: Rheum palmatum, Scutellaria baicalensis, licorice root, and Cnidium monnieri. I couldn't find any information about how much of any of these was actually in the product.
Right now I have eczema in a number of places including the backs of my hands. I rubbed Kamedis lotion into my left hand, and used the usual stuff on my right hand: Eucerin and Aveeno. I tried this for three days. I saw no difference between my right hand and my left. (No improvement in either.)
As weak as my trial was as a scientific exercise, I did better than Kamedis in one respect: I used a control. Kamedis tells me they have conducted a clinical trial that shows their lotion improves symptoms in 20 patients with eczema. They did not use a control group: either a group that received no treatment or a group that received a standard treatment. Therefore their trial is of no value.
This prompted me to look at how TCM herbs regulated in the United States. I hadn't thought about this before. I was surprised--and appalled--to learn that to a great degree TCM herbs are not regulated at all.
Amazing, isn't it? Drug companies pay huge settlements when it turns out that a new drug has a fatal side effect in a tiny subset of users. Drugs must undergo an enormous battery of tests to verify efficacy and non-toxicity in animals and humans. Drug manufacturers employ stringent quality control to ensure the same dose is in every pill or ointment. TCM herbs don't have to pass any tests. We're supposed to rely on folk wisdom and the goodwill of the company selling the product.
We can thank the Dietary Supplement Health and Education Act of 1994 (DSHEA) for tying the FDA's hands when it comes to regulating dietary supplements. The Kamedis lotion isn't a supplement, it's a cosmetic, and the FDA is supposed to regulate cosmetics, but TCM falls into a category that isn't controlled strongly if at all--and I am sure there are loopholes that companies can use to get pretty much any products on the shelves in stores or on the internet.
If anyone knows more than I do about TCM regulation in the United States, I would appreciate clarification.
I remain appreciative of TCM's potential, but it is a jungle out there. There's way too much potential for quackery (expensive placebos), danger for side effects and drug interactions with TCM components and conventional therapies. And even if you have the right TCM herb, how can you ensure the same amount of active ingredient is in each batch?
I appreciate the opportunity Kamedis gave me to test their lotion--at the very least, it alerted me to four herbs that (I'm guessing) TCM practitioners have used over the ages to treat eczema. Maybe one or more of them contain novel molecules that can be formulated to provide real, quantifiable benefit.
Herbal medicine, though, is a major foundation of modern pharmacy. TCM herbs contain molecules that are biologically active--what Western medicine would call drugs.
This is why I doubt that the TCM practice of dosing with several (sometimes nine or ten) herbs in combination is a good idea. The potential for side effects and drug interactions is too high.
I acknowledge that empirical, practical knowledge is a powerful way to solve problems, and that TCM could work for certain conditions in the right circumstances. You would need to have a very experienced TCM practitioner treating a patient for a condition that the expert was familiar with. You could get results--even though the theory is bunk.
But I am skeptical when companies market TCM herb-containing products directly to consumers. The treatment can't be tailored to the patient. The dosing and quality control are dubious. How do you know what the active ingredients are, and are they consistent from batch to batch?
And most importantly, who has verified that these things work and aren't toxic?
Recently I was asked whether I would review TOPICMedis Calming Lotion, a product of the Israeli company Kamedis. The lotion contains four TCM herbal extracts. I was intrigued, and agreed--because I wanted to learn which TCM herbs might be useful in treating eczema.
So what's in TOPICMedis Calming Lotion?
The first three ingredients listed are "water, glycerin, dimethicone & cyclotetrasiloxane & polysilicone-11."
I like dimethicone. It's a rubbery polymer that Aveeno includes in their Daily Moisturizing Lotion and I find it seals moisture into my skin. Not exactly a traditional herb though.
The lotion contains extracts from four herbs: Rheum palmatum, Scutellaria baicalensis, licorice root, and Cnidium monnieri. I couldn't find any information about how much of any of these was actually in the product.
Right now I have eczema in a number of places including the backs of my hands. I rubbed Kamedis lotion into my left hand, and used the usual stuff on my right hand: Eucerin and Aveeno. I tried this for three days. I saw no difference between my right hand and my left. (No improvement in either.)
As weak as my trial was as a scientific exercise, I did better than Kamedis in one respect: I used a control. Kamedis tells me they have conducted a clinical trial that shows their lotion improves symptoms in 20 patients with eczema. They did not use a control group: either a group that received no treatment or a group that received a standard treatment. Therefore their trial is of no value.
This prompted me to look at how TCM herbs regulated in the United States. I hadn't thought about this before. I was surprised--and appalled--to learn that to a great degree TCM herbs are not regulated at all.
Amazing, isn't it? Drug companies pay huge settlements when it turns out that a new drug has a fatal side effect in a tiny subset of users. Drugs must undergo an enormous battery of tests to verify efficacy and non-toxicity in animals and humans. Drug manufacturers employ stringent quality control to ensure the same dose is in every pill or ointment. TCM herbs don't have to pass any tests. We're supposed to rely on folk wisdom and the goodwill of the company selling the product.
We can thank the Dietary Supplement Health and Education Act of 1994 (DSHEA) for tying the FDA's hands when it comes to regulating dietary supplements. The Kamedis lotion isn't a supplement, it's a cosmetic, and the FDA is supposed to regulate cosmetics, but TCM falls into a category that isn't controlled strongly if at all--and I am sure there are loopholes that companies can use to get pretty much any products on the shelves in stores or on the internet.
If anyone knows more than I do about TCM regulation in the United States, I would appreciate clarification.
I remain appreciative of TCM's potential, but it is a jungle out there. There's way too much potential for quackery (expensive placebos), danger for side effects and drug interactions with TCM components and conventional therapies. And even if you have the right TCM herb, how can you ensure the same amount of active ingredient is in each batch?
I appreciate the opportunity Kamedis gave me to test their lotion--at the very least, it alerted me to four herbs that (I'm guessing) TCM practitioners have used over the ages to treat eczema. Maybe one or more of them contain novel molecules that can be formulated to provide real, quantifiable benefit.
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