The "itch receptor"

Another thing for me to be excited about: this Thursday, I get to talk to Gil Yosipovitch, the "Godfather of Itch," who runs a clinic at Wake Forest University and founded the International Forum for the Study of Itch. (I made him an offer he couldn't refuse.) If you have any questions for him, please ask and I will pass them along. Myself, I just want to get an idea of how his clinic operates, and find out why there aren't more of them.

Also, whether he envisions any pharmaceutical cures for itch appearing soon. Martin Steinhoff scribbled a list of possible targets in the itch pathway that one might like to shut down to reduce or eliminate itch. Here's what he wrote down, before I distracted him with another question:

• GABA
• GRP
• Proteases

The "GRP" rang a bell in my memory so I looked it up. It stands for "gastrin-releasing peptide," whatever that is. What's important is that in 2007, two scientists at Washington University in St. Louis discovered that a receptor for GRP is a major gate for itch nerve impulses in the spinal cord, at least in mice. (And basic neurology isn't different in mice and humans.) I could be wrong, but I think that GRP receptor is still the prime suspect.

The scientists were able to do their experiments because they had developed a strain of mice without GRP receptors. These mice were much less likely to scratch themselves when their skin was injected with substances known to induce itch. And in normal mice, a compound that inhibits GRP receptors greatly reduced scratching behavior.

This isn't exactly breaking news, but it is good for me to know as I explore "itch centers" in the US and around the world.

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A wee  bit of business news: a small company in Seattle, recently acquired by Bristol-Myers Squibb, is developing an anti-IL-31 antibody which is now in preclinical trials for atopic dermatitis. (Now, what does IL-31 do? I always get confused by these IL-X things. It is apparently produced by Th2 cells and has something to do with inflammation.

How an "itch center" (or clinic, really) would work

After I wrote the last post, I realized that I should clarify what I mean by "itch center." If you search for the term on Google, you don't turn up much, but I did find one indirect listing for the "Center for the Study of Itch" at Washington University in St. Louis, Missouri. It has something to do with the Washington University Pain Center. Anyway, what I mean by "itch center" is a place that primarily serves patients, rather than a pure research lab. As far as I know there is currently only one such entity in the U.S., Gil Yosipovitch's at Wake Forest University in Winston-Salem, North Carolina. And you can't find a webpage for it. How is a patient supposed to get help?

Martin Steinhoff told me that he plans to establish an itch center at UCSF--a clinic to help patients. He also mentioned, in conjunction with that clinic, that he's putting together a research center. You might be interested to know how these things get planned.

For his clinic, to begin with, Steinhoff would serve as the lead doctor with three residents working under his direction, plus one nurse. In Germany, he says, with such a setup he was able to see 50 patients in a day. At UCSF, he says he wants to think on a bigger scale, so eventually there may be several senior doctors and many residents and nurses.

As I mentioned in the previous post, Steinhoff says that at his Muenster clinic the most important feature was that patients would arrive for diagnosis and spend the next one or two weeks under close supervision so that their treatment could be adjusted according to need. In the US system this can't happen (barring unusual philanthropy)--doctors usually see ambulatory patients only for very short times, and then send them away for 4-6 weeks.

Steinhoff says that he's thought about this--the limitation is frustrating, but he thinks that he could achieve some sort of active modulated treatment by having patients join a self-help group, moderated by the clinic's nurse. The patients could check in to a website or wiki online where the nurse would be available several hours a day to check how people were doing, and in off-hours they could converse with each other in forums. I'm extrapolating here, but I expect his idea is that the patients would lend each other moral support as well as practical advice. It'd be interesting to see this in operation--how much of the forums would consist of comments like "OMG I'm so itchy" or "Just scratched, feels so goooood"? Probably knowing that the conversation was moderated by the nurse would improve the tone.

In Steinhoff's proposed itch research center, he'd again be the director, with, to begin with, two assistant professors in his laboratory. (He's an active research scientist and in fact got his PhD in biology before his MD.) I'd like to visit his laboratory sometime to see how one carries out itch experiments, but I've used up my quota of his valuable time for several months.

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You may have noticed that I am posting less often at the moment. My current target is twice per week. I've been having some back trouble that may have been brought on by my enthusiastic start to blogging--until recently the ergonomics of my home computer setup were terrible, and I'm now at about 75 posts, so that makes about two days' straight worth of typing with bad posture. My physiotherapist has advised me to make several changes to my lifestyle, and seeing as I already spend 8 hours a day in front of a computer at work, it doesn't make sense to overdo it at home.

Martin Steinhoff plans largest itch center in the world

Today I met with Martin Steinhoff, a professor of dermatology at the University of California, San Francisco (UCSF). (He's listed as a "professor in residence," but assures me he's here to stay.)

Steinhoff plans over the next 25 years to build the biggest "itch center" in the world at UCSF. Previously he led the itch clinic at Muenster, which he believes is the largest such center in Germany. An itch center is a special clinic with dedicated residents and staff, at which patients are diagnosed, treated, and observed intensively over a period of one to two weeks, and their treatment modulated to get the itch under control.

Steinhoff came to UCSF because he was impressed with the research being done in neuroscience. UCSF is a purely medical and research campus with no undergraduates--it used to be the medical school of UC Berkeley, and although not well known to the public, it is the second largest recipient of NIH funds (presumably after Johns Hopkins in Baltimore). However, he says he is the only itch specialist currently at UCSF, although he works closely with four scientists who study pain, which shares neural pathways with itch.

Steinhoff has been impressed with the can-do, entrepreneurial spirit in California. "Here you have the possibility to build a computer company like Apple in your garage," he says. "In Germany, people expect everything from the government."

However, he prefaced those remarks with ones less likely to be repeated by American politicians. He is frustrated and unimpressed with what passes for a fragmented health care "system" in the US. Because of the power wielded by insurance companies, itch patients in particular receive substandard care. "In Germany, when a patient visits [the itch clinic], they come for one week, get a diagnosis, and we get it under control," he says. Here, you are seen for two minutes--maybe 15, at a university--you get a quick diagnosis and you're told to come back in 6 weeks. There is no time. And because of money, you cannot prescribe the optimal treatment, because of insurance." [This is true for me, actually: my own insurance wouldn't pay for me to attend Steinhoff's proposed clinic.] "

"In the US, insurance wants to prescribe the cheapest topical or systemic steroid," he says, even if the best treatment would be a large dose of (admittedly expensive) nonsedative antihistamines. [A surprise to me, this; I'm not the expert, but I thought antihistamines were not effective. Maybe just the ones I've taken.] His conclusion: "You cannot help patients because of the insurance."

Whatever your political views, you'd have to agree that the point of health care is to help the patient, and from that perspective, the current "system" is broken.

I'll give a few details of Steinhoff's proposed clinic in the next post, and how he plans to work around the limitations. I'd just like to add that he's a little mystified why eczema has such a low profile in the US, while conditions such as psoriasis that, according to him, "have much less effect on quality of life," are well-known. Once he gets his clinic off the ground, it will be only one of two such centers in the US, the other one being Gil Yosipovitch's at Wake Forest University. Two centers for 240 million people in the richest country in the world.

Most definitely no definite answer for vitamin D and eczema

As with most of the posts on this blog, I wrote the last one in a hurry--there's only so much free time if you've got a job and a commute and two kids. Being in a rush makes blogging unsatisfying as a writing exercise, both for the strength of argument and the quality of prose. A blog is nothing more than a series of first drafts, and the expression "shitty first drafts" (Google it) exists for a reason.

So I thought perhaps I'd been too quick to diss vitamin D as potentially having benefit for patients with eczema. A PubMed search turned up this review paper, which I am inclined to trust as credible for several reasons:

1. one of the two authors is Donald Leung, head of pediatric allergy and immunology at National Jewish Health Center in Denver; editor-in-chief of the Journal of Allergy and Clinical Immunology; and principal investigator for the Atopic Dermatitis Research Network
2. the authors cite 73 papers instead of just one or two selected to support their cause; they present a balanced view with opposing data
3. they don't use scary headings like "Is This Nutritional Deficiency Ruining Your Heart?" or provide a convenient link to an online store with products such as krill oil, vitamin spray, and bidets.

Anyway, I learned quite a bit. In short, vitamin D deficiency is a real phenomenon in the US population. There are a number of molecular mechanisms in which a lack of vitamin D might increase the severity of eczema. And a few trials have been done with small numbers of people that show that a short course of increased vitamin D improves symptoms.

That's not enough to make me rush out and buy barrels of vitamin D though, especially since there are multiple side effects of an overdose, including kidney damage. As Caroline commented after my last post, the issue is really whether you're deficient or not, not that it's a good idea to take an excessive dose. (I sent her a copy of the paper so we can look forward to learning her perspective.)

A reading of the paper turns up a bewildering number of studies in cells and mice that produced conflicting results. E.g. mice deficient in vitamin D had helper T cell responses greatly slanted toward type 1 instead of type 2; but it's known that, in humans, eczema patients have overactive type 2 helper T cells. If you were to take that one paper as gospel, you'd try to deprive yourself of vitamin D to cure your eczema.

Another paper shows that adults who received vitamin D supplements as infants were more likely to develop atopy and allergy. But then opposing papers balance this out. Dosage and timing could be crucial.

So, as with most science, the conclusion is the familiar "more research needed."

Vitamin D isn't the answer

In a recent conversation with Caroline over at Fighting Eczema, she mentioned that she wanted to look into whether having low levels of vitamin D might be correlated with risk of developing eczema. The theory was her own, but she mentioned "a strong advocate for the benefits of vitamin D on the internet, Dr. Mercola." I thought I'd check the man out, since I'd seen another article or two by Mercola in the general health news.

I was seriously unimpressed. Joseph Mercola is a self-appointed "expert" on "natural health" who, in short, is a scaremonger peddling fears of modern technology and the drug industry. Natural cures are best, he says; and just in case you were wondering where to get them, you need only visit his extensively stocked online store.

He's big on vitamin D, for sure; has an entire section devoted to it. According to him, it cures just about everything. Count me a skeptic. Every doctor I've asked, and a few I haven't, has told me that anyone eating a balanced diet has no need of any vitamin supplements at all. Vitamin C, and perhaps a few others, are flushed out of your body in your urine, but the rest accumulate in your tissues. Too much of a vitamin or mineral is a bad thing, just like too little. No way would I take an excessive dose of one particular substance unless I'd been diagnosed with a severe deficiency.

(Amusing aside: in my 20s, for a short while, I took several multivitamins a day, in the belief they would make me super-healthy. I developed a remarkable case of hemorrhoids that cleared up when I stopped taking the pills.)

Caroline, I mean no offense--in the search to cure eczema for our children and ourselves, we ought to explore every avenue. But vitamin D isn't going to be the answer.

If you're interested--I recommend it--the blog Science-Based Medicine has a comprehensive and entertaining takedown of Mercola. Here's one segment. The FDA has served Mercola with two warning letters concerning unwarranted claims for seven of his products.