Monday, January 30, 2012

Itch, and scratch relief, depends where it is on the body

A new study [media summary] by itch guru Gil Yosipovitch and colleagues at Wake Forest University has shown that the intensity of itch, and the pleasure of relieving it by scratching, depends on the precise location on the body that a standard itch stimulus is applied.

In standard studies of itch (and, one would presume, creams and ointments designed to relieve it) the usual site of focus has been the underside of the forearm. But Yosipovitch and colleagues, who compared itch on the forearm, the back (slightly to one side of the spine, near the middle) and the ankle, find that itch is sensed more intensely on both ankle and back, and the pleasure of scratching lasts longer on the ankle--even after the itch has dropped off--than on the forearm.

They used "cowhage spicules," which I think are akin to nettle spines, to cause the itch, and a standard laboratory scratching brush to relieve it in 18 volunteers. The paper, which is open-access, doesn't mention whether any of the volunteers had eczema. This matters, I think, because you'd expect eczema patients to perceive and respond to itch differently than "normal" people.

The authors, in their discussion section, speculate on why itch intensity and scratch relief differ across the body. They discuss various types of nerve fibers that might be responsible, but come to no conclusion. Really the paper just poses a question: why are these differences there? And we could expect, in following work, that they might narrow the answer down to the presence or absence of nerve types. It's clear that the mechanism of itch and relief is far from understood.

[It occurred to me later that maybe this research points to the need for different anti-itch treatments for different parts of the body. Whether they work or not, I can imagine companies claiming that various ointments and creams are optimized for your hands or whatever.]

Friday, January 27, 2012

A venture capital fund for eczema companies

Today I had a crazy idea about something to do to get us closer to a cure for eczema.

What if we created a venture capital fund devoted exclusively to investing in startup companies developing eczema therapies? Therapies could include new drugs (oral, topical); new barrier creams; new itch-inhibiting devices, etc.

Venture capital firms invest in small-to-medium size companies that look like they have the potential to grow big in a hurry. Venture capitalists accept a fair amount of risk; perhaps 9/10 of their investments will prove failures, but that tenth one will go off like a bomb and multiply their money a hundredfold.

Small companies need venture capital to build value to the point where they can get acquired by a larger company or hold an initial public offering of stock.

The conventional wisdom that you need to diversify your portfolio, so my idea may come across as foolish. I haven't heard of a specialized one-disease fund before. There could well be some out there and I'd like you to tell me if you know of any. Despite  conventional wisdom, my naive experience with investing over the past few years has taught me that the whole market goes up or down in unison like a herd of lemmings. The only exception to this is gold, which goes the opposite way to everything else. So I don't think an all-eczema investment fund is necessarily a losing proposition.

It could be structured as one big investment (say from a philanthropist) or lots of smaller ones. For a first fund, I'd aim for $10 million, and it would probably be best to have 10 investors at $1 million apiece so you don't have one big boss dictating what you do.

The fund would aim to invest about $500,000 in 20 different startup companies across the U.S.

(My model for this idea is a small fund called Mission Bay Capital, the operations of which I am familiar with.)

The key to getting started, to being able to pitch successfully to investors, is to have a solid business advisory board. I expect I could convince some of the National Eczema Association's scientific board to back this fund as advisors, but this is not what I'm talking about--I mean seasoned venture capitalists from Silicon Valley. If you had $1 million to lend out, who would you give it to: a scientist, or a successful businessperson? Face it, you only lend money to people you feel comfortable with--people who know how to make a profit.

And the fund would be for profit. It would exist to make money for its investors. You'd have to pay the manager a fee too. But the plan, in the end (after, perhaps, launching a second fund of $100 million) would be to return a certain fraction of the profit to the NEA to support eczema research.

An eczema venture capital fund could make money and help produce needed therapies for us all.

Am I nuts or what? I'm going to think this through some more. It's absolutely necessary to connect to one or more successful people in Silicon Valley who have personal experience with eczema.

Wednesday, January 25, 2012

More on habit-reversal for eczema treatment

After meeting Mei and CK Bridgett on Twitter I have done a little bit of research on the "habit-reversal" technique Bridgett is so keen on for eczema patients.

I like the idea very much. Through my entire life the only attitude I have gotten from doctors (GPs and dermatologists) about my eczema is that there's nothing you can do for the patient except prescribe topical corticosteroids. Nobody has ever addressed nervous or compulsive behavior, which is certainly a component.

In his website/book, Bridgett, a psychiatrist, refers to a number of the original papers on the habit-reversal technique. I printed them out and read them, and you can too.

A 17-patient study, finding that behavioral change (clenching hand into fist, or grasping an object) plus hydrocortisone cream improves skin quality twice as much as hydrocortisone cream alone (but did not affect bouts of intense itchiness).

A 45-patient study, where behavior training (fist-clenching &/or pinching the itchy area to cause pain) + steroid reduced scratching by 90% compared with 75% for steroid alone.

A conversational speech by Peter Noren, very readable, in which he explains how parents can apply the technique to children. Noren rightly laments the poor attitude of many doctors and insists on a positive outlook by both doctor and patient, and deeper involvement by the doctor.

I have to say that these studies are pretty small in size. I wonder whether anyone's ever conducted a study of, say, 200 or 1000 patients, which would give you more confidence in the results. Soon I hope to conduct a very small study (one patient: me) and publish the results on this blog. What's stopping me? I have to get psyched up to make little marks on a piece of paper each time I scratch, and to poke my skin with my fingernail in public.

Last year I spoke to Martin Steinhoff about his plans for an integrated itch center at the University of California, San Francisco (where I work). At the time Steinhoff did not mention behavioral coaching, but I'd like to ask whether he would consider a psychiatrist or behavioral coach as an essential member of such a center.

Friday, January 20, 2012

Control obsessive scratching using psychology

This morning I washed my hair (or what's left of it) with tar shampoo. Rubbed some jojoba oil into my scalp, but a few hours later at work I found myself absent-mindedly picking at scabs and dry skin on my head. I wasn't even itchy. It was a bad habit, a sort of obsessive compulsion, which I've had for many years, and which is exacerbated by stress. And with modern life, there's no shortage of stress. Deadlines! Email! Car trouble!

The picking and scratching start up the vicious cycle of eczema--the itch irritates the skin, which generates more itch, which means more scratching. You'd think there'd be a way to break the cycle at some point--where the itch is psychological, and perhaps subject to more control than physical itch. OCD-type scratching is the one aspect of eczema that can be blamed on the patient.

And in fact there IS a method that doctors have developed in the clinic to control psychological aspects of eczema. It's not new, but it's new to me. It's called "habit reversal", and it's employed by Christopher  Bridgett (on Twitter as @ckbridgett. He gives good tweet) at Chelsea & Westminster Hospital in London. I'm sure other doctors use similar techniques elsewhere.

Hat tip to @MarcieMom on Twitter, on whose excellent blog Eczema Blues I learned about Dr Bridgett.

Habit reversal was originally developed in Sweden in the late 1980s, based on earlier work in the US. You can find most of the details here. In fact you can (as I have done) print the pages out from the book, "Atopic Skin Disease: a Manual forPractitioners," by Christopher Bridgett, Peter Noren, and Richard Staughton.

Habit reversal, applied to eczema, consists of four basic elements:
  1. the patient "registers" the behavior, using a clicker or some form of counter, to count the number of times he or she picks or scratches throughout the day. This is key because to control the behavior one must be aware of it. (I often find myself scratching, having started unconsciously.)
  2. thereafter, when the patients realize they have the urge to scratch, they try clenching their fists--this stimulates the motor neurons and muscles involved in scratching.
  3. if this doesn't work, the patient tries pinching the itchy area, or poking a fingernail into it, to provoke pain that quells the itch.
  4. later, the patient follows up with the doctor, who prescribes steroids or other anti-inflammatories to reduce itch that can't be controlled using the first two methods.
The authors report a study in which scratching frequency was reduced by 90% after four weeks in a group using this method (habit reversal + steroids) versus 70% for a group using just steroids.

Sounds like a good thing to try. I have to figure out how to apply it to myself. There’s got to be an iPhone app out there that I can use as a counter!

Monday, January 16, 2012

A worldwide look at drug therapies for eczema

A market research company has just released a new report analyzing the market for eczema therapeutics and predicting how the field will change over the next six years.

The report, titled "Eczema Therapeutics - Pipeline Assessment and Market Forecasts to 2018", can be yours for only $3500.

This type of market research is carried out by independent companies that sell their work to other companies large and small. Because they're providing a commercial, fact-based service, you can expect that they've done a thorough job.

Decisions that companies make based on reports like this explain the gap between what eczema patients need and what actually makes it to market. No matter whether it's feasible to develop a drug, because the cost of taking a chemical compound from discovery to FDA approval is around $1 billion, no company is going to invest in developing a drug that doesn't promise to pay its way and then some.

I tried to get a copy of the report--when I tweeted about it, got a direct message inviting me to apply for my free sample--but when I did, I was asked to pay $3500 upfront. D'Oh! It was unreasonable to expect the market research company to give their product away for free, especially to someone who clearly intends to blab all over the internet.

So we're left trying to deconstruct the table of contents for whatever meaning we can squeeze out of it.

The authors have segmented the globe into the leading national markets: the US, France, Germany, Italy, Spain, the UK, and Japan. I wonder why this order was picked--you'd think that Japan would rank higher than Spain, just because of the population size.

Why have they done this? What's different about the national markets? No surprise that the US leads, nor that all of them are developed Western countries. I suspect, because eczema prevalence seems to track the level of a nation's economy, that the markets are not different because, say, people in France need different therapies than people in the US. But governments regulate drugs differently. French companies--like Sanofi--and their products may enjoy preferential tax treatment in France. Or perhaps European companies are privileged in Europe.

This matters to you, the patient or parent, because you can't assume that the country you live in necessarily has the best therapies available to you. Maybe you live in the UK, but the eczema you have is a variety that is prevalent in Japan, and the Japanese market features therapies that would work best for you. Maybe you should be lobbying your own government to approve those therapies at home. Regional differences in therapies is an area that I am now going to pay attention to.

The authors have also kindly identified the leading companies in the eczema therapeutics field. They are Almirall, Anacor Pharmaceuticals, BioCis Pharmaceuticals, MIKA Pharma GmbH, Novartis AG, GlaxoSmithKline, and Sanofi.

This is useful because, to average Joes like me, the pharmaceutical world seems an unknowable universe where every company makes every kind of drug. But that's not the case. (Where's Bayer in this list? J&J?) Even in big pharma, companies have their cash cows (e.g. Pfizer and, until recently, Lipitor) and their areas of technical expertise. From now on I am going to pay attention to which companies have what products coming down the pipeline. The results of clinical trials, if not published in the business section, are usually sent out in press releases that you can find online.

Interested to learn what, globally, the leading drug therapies for eczema are? I bet you haven't heard of some of them. Protopic (tacrolimus), Elidel (pimecrolimus), MimyX, Atopiclair, and, of course, the whole gamut of topical corticosteroids. I'm going to look more closely at MimyX and Atopiclair, to start. I wonder what they are, what they do, and where they're approved for use.

Thursday, January 12, 2012

Common antibacterial also suppresses mast cells--maybe why it works for eczema

Triclosan is a well-known antibacterial found in soaps. I know I've seen it listed on every pump-container of liquid soap that claims to "kill 99% of bacteria," whatever that means. (99% of species? 99% of one species?) What I didn't know until recently about triclosan, which is found in a wide range of consumer products, is that it relieves symptoms of eczema. But scientists are not sure exactly how it works.

New research by scientists led by Julie Gosse at the University of Maine shows that at least one reason that triclosan helps reduce eczema symptoms is that it prevents mast cells in the skin from releasing histamine and other allergy-mediating molecules. Triclosan prevented the scientists' model cells from getting activated in general. In short, it's an immunosuppressant.

Mast cells have molecules on their surfaces that bind to IgE antibodies--the type responsible for allergic hypersensitivity. When mast cells encounter antigen, perhaps from food or pet dander, they release histamine and other molecules, which cause inflammation.

The scientists, working with a laboratory cell line that they claim is identical to mast cells, found that doses of triclosan significantly reduced the amount of one molecule, beta-hexosaminidase, released by the cells when they met antigen.

Activated mast cells change shape, ruffling around the edges. Triclosan also prevented this from happening.

The scientists claim their results show that reducing "degranulation"--the release of granules stored by mast cells--is the way that triclosan helps alleviate skin inflammation in eczema.

Through the paper, the authors refer to histamine--but reducing histamine probably isn't the main avenue by which triclosan acts. If you have eczema, you know that antihistamines don't help. I don't know why some doctors prescribe them. Relatively recent research (I wrote about it here) has identified a neural itch pathway independent of histamine.

So what good is this research?

It helps clarify the picture of what triclosan is doing. It's a contribution that could, in the end, help produce another topical anti-itch ointment that incorporates triclosan or some derivative, possibly together with a steroid. You'd think it'd be a no-brainer, because of its antibacterial properties. But, like any drug, triclosan comes with its own side effects.

[Edited Jan.13]

Saturday, January 7, 2012

Controlling scratching and modeling how to behave for your kids

If you've got eczema, you scratch. And sometimes you scratch in front of others--either you're not aware that you're doing it, or you are but you're nervous, or you've just got that itch that needs dealing with. You can control it when you really need to--say you're on stage presenting a talk at a conference. As soon as you're out of the spotlight, you give in to the urge.

But sometimes you get called on it. "Hey, why are you scratching?" Or you can tell someone's noticed. And that's embarrassing. Because it's not socially acceptable to do it in public. Like picking your nose or masturbating, scratching is something that most people do privately if they want to keep their jobs and spouses.

So how do you explain to a child with eczema that they should try not to scratch in public? Given, of course, that some outbreaks are unbearably itchy and you can't help yourself. I'm talking about scratching that you could control if you wanted to.

This hasn't come up as an issue for us yet, but I've been thinking about it. You know that just telling your kids to do something is not enough.You have to model the behavior yourself. I know this well. Just this week (as a New Year's resolution) I started eating raw vegetables, instead of my usual chips or chocolate, in front of the kids during their dinnertime. Whaddya know? All of a sudden Voov wants a carrot stick. Shmoop can't get enough kohlrabi.

If Voov, currently two and three quarters years old, grows up with eczema, as she shows every sign of doing, I'd like her not to scratch unduly in public. They'll eat you alive in high school for that. So, as her eczema-afflicted dad, I need to try not to scratch in front of her.

I admit it. Around my kids, I usually behave as if they're not even there, when it comes to personal matters. When your kids like to barge into the bathroom and closely examine your butt as you're toweling off after a shower, it's hard to follow Miss Manners' code of conduct once you're fully dressed. So I often find myself vigorously scratching my feet, or picking at my scalp, in front of Voov.

Really, I need to smarten up and stop this; act as I would in front of my boss. Because the only way she's going to know how to control herself, to the extent it's possible with eczema, is if I show her that it can be done.

I'm hoping I can speak to a behavioral expert about this and learn some tips about controlling compulsive scratching--an issue that I wouldn't be surprised to learn is connected to OCD. If I do learn anything, I'll blog about it.

Wednesday, January 4, 2012

Three new eczema mutations discovered. Is this useful?

A large-scale genetic study recently identified three new locations in the human genome at which mutations are linked to eczema. Two of the locations are near genes thought to be important in dividing and developing skin cells; the third is near a cluster of genes involved in chemical signaling.

The study was published in Nature Genetics, a high-ranking journal. It is actually a meta-study, which re-analyzes data from 30 other studies, totaling more than 11,000 people affected with eczema and more than 40,000 unaffected controls. I don't know how meta-studies account for all the differences in methods and objectives, but I am impressed with the numbers. Generally when it comes to genetics bigger is better.

The question for a patient is: how is this information going to lead to a therapeutic (e.g. new drug)? At this point the researchers don't even know what the genes in the mutated regions do. (None of the mutations were actually IN genes; they were in regions BETWEEN genes.) To get to a therapeutic, you'd have to identify how the mutations affect proteins, what the proteins do, and find drug targets on those proteins, screen for drugs that work, and proceed through the whole billion-dollar death march to FDA approval.

Basically, we're not going to see something in our lifetime from this. Our kids might though.

The authors do at one point say "These the claim that atopic dermatitis encompasses distinct disease entities rather than being one illness, as is reflected by the current, relatively broad and inclusive concept of this condition." It is possible that within a decade or so we could see direct-to-consumer genetic tests that could tell you what subtype of eczema you suffer from, and you or your doctor could use this information to pick a treatment that might be more effective.

The Eeyore within me says that I'd most likely find that my type was the least treatable. Would I want to know this? Curiously, yes. I found out a few years ago that I carry one copy of the most common mutation for cystic fibrosis. Not good news, but it gave me a small sense of power to have the information.