Three years of immunotherapy enough for dust mite allergy

Dust mite allergies are a common trigger of eczema flares for many. Dust mites--tiny relatives of spiders--thrive in bedding because they eat flakes of skin. And with the amount of skin that flakes off when you have eczema, it's a catch-22 problem.

From what I can find out, dust mite feces is the major source of their allergens. Eww!

One solution is to get allergy shots: regular injections of allergens at low doses that cause your immune system to develop a tolerance over time. I don't know what the regimen is--how many shots, and when you have to get them--but it is undoubtedly a hassle. Certainly it goes on for years. Doctors have debated how many years, some saying that five were required. A new study concludes that three years is enough. (Not a regime you're going to start on a whim.)

I asked the study's author, Iwona Stelmach, a professor at the Medical University of Lodz in Poland, for a copy of the paper, but haven't got one yet, so all I know is what I've read in the press release and the paper's abstract. It seems that the researchers worked with a three-part study group, totaling 90 asthmatic children, 30 each of whom had either had no immunotherapy, three years of immunotherapy, or five. While immediately after therapy, the five-year group needed less steroid to control a reaction to dust mite allergen, by the time three years had passed, the three- and five-year groups were essentially the same.

If you've got a severe dust mite allergy (and congratulations on figuring that out), it must be a relief to know you only need three years of allergy shots instead of five.

Lymph node immunotherapy may be simpler, safer

A new, improved method of immunotherapy is emerging: injection of modified allergen, directly to the lymph node--which promises to prevent allergy to specific triggers with only a few treatments and minimal risk.

A group of Swiss, German, and Swedish scientists reports in the latest issue of the Journal of Allergy and Clinical Immunology that they reduced nasal tolerance of cat dander, a major trigger for atopic allergy, by a factor of 74 in a group of 20 subjects, using only three injections over two months. That means it took 74 times as much dander to cause the same amount of allergic reaction--the scientists used the flow of liquid from the nose as their measure--in a treated person as in a subject given placebo.

[This article featured in JACI's Journal Club.]

Immunotherapy for specific allergens currently requires 30 to 80 injections over three to five years and includes a risk of anaphylactic reaction. It is not popular. The new method, if confirmed, looks much more practical.

The researchers, Gabriela Senti of University Hospital Zurich and colleagues, were basically repeating an earlier, successful study that they had done with grass pollen. (I consider cat allergy avoidable but grass pollen is a big deal--you can't get away from it, unless you're in Antarctica.)

But the new study came with a twist--the researchers modified the cat dander allergen with two molecular changes. The first added a short chain of amino acids that helped the allergen enter the cell membrane--essentially, the membrane of B and T cells, since it was injected into the lymph nodes. This seems to have prevented other white blood cells, such as macrophages and mast cells, from encountering the allergen and provoking inflammation.

The second modification ensured that the allergen didn't get immediately destroyed inside the cells, but instead got chopped up and presented on the surface of antigen-presenting cells, which are a key element of the antibody arm of the immune system. Thus, by a process I don't really understand, your immune system becomes "tolerant" to that allergen.

Treatment with the modified cat allergen did not increase IgE antibody levels, or induce any "adverse events" in the treated group, which, it has to be said, numbered only 12. It's possible that in a larger test group some problems might reveal themselves.

If an environmental allergy is a big problem for your eczema, and you can stand nurses injecting things into your lymph nodes, this looks like good news. I don't know how long it might be until the FDA approves this treatment in the US though.

A close-up look at immunotherapy

January's issue of the Journal of Allergy and Clinical Immunology is dedicated to immunotherapy. To be honest, the first time I heard of immunotherapy, I thought it was a quack treatment (it didn't help that what I'd heard of was sublingual immunotherapy, and the point of the author was that because the FDA hadn't yet approved it in the US, it must be too effective). But the more I learn about it the more I find that it is a long-established therapy with proven results. You should read the issue's editorial, which summarizes immunotherapy over the past 100 years.

What did I learn from this issue? (Not: what is news to everyone; what was news to me.) First, it seems that immunotherapy is largely directed at allergic rhinitis, or hay fever, caused by grass pollen; that, in the US, the standard method is repeated injections over a long period, from four months to three years; that sublingual immunotherapy is widely practiced in Europe, and appears safe and effective; and that trials of therapies for other allergens such as cat dander and dust mite droppings are being conducted and show promise.

For now let's leave aside the issue that doctors don't seem to be prescribing immunotherapy for eczema patients. Say it were available. What then?

The problem for me is that I don't know for sure what allergens cause my eczema. I know that my skin prick test, 10 years ago, showed that I reacted to a bunch of things including cat (at least, one cat allergen), egg white, and rye grass. But does that guarantee that, say, rye grass pollen is a major factor in my eczema during the period that rye grass pollen is in the air? Everything I've read regarding food allergies says that skin prick tests are not diagnostic, and that the gold standard is to lay off the offending food and see if the problem goes away. There's no good way to try an avoidance diet with pollen or dust mites.

An aside: the reaction I get in the spring and summer, which I attribute to pollen, is quite different from the eczema I experience on my hands, arms, scalp, etc. In the summer, on both east and west coasts, I get red, inflamed skin on my face in a butterfly pattern. It's distinctive, and out there in the open for everyone to see. I saw the same pattern once on someone else's face.

One thing I am sure of: Claritin and Allegra, the over-the-counter antihistamines marketed for hay fever, do absolutely nothing for me.

Would I undergo injection immunotherapy, a long, arduous, and (in the US) expensive procedure, in the hope that 1) the thing I'm getting injected with is a major contributor to my eczema and 2) the therapy works for me? No, I wouldn't. And I do suspect that at least one form of pollen gives me trouble.

But I would take a course of immunotherapy tablets orally (or sublingually). That would not seem like a waste of time, nor would it be hard to get a kid to take them. One good thing is that grass pollens are, apparently, "cross-reactive," which I read as meaning their allergens are similar enough that if you induce tolerance to one, you induce tolerance to the rest of them. So you don't have to take more than one type of allergen as immunotherapy.

Reading the editorial, I did learn that grass pollen tablets are not effective if you take them as only one component of a mix of allergens in immunotherapy. Here's another difference between the US and Europe: in the US, a multiallergen mix is a common approach, while in Europe, immunotherapy for a single allergen at a time is the norm. (Any experts or Europeans are free to correct me on this.) So, it does appear that the US is lagging Europe in easy, effective immunotherapy.

When will we see immunotherapy applied to eczema? Is there anywhere in the world where it already is?

Ain't he cute?

Not too much to post tonight-- I'll note that the current issue of the Journal of Allergy and Clinical Immunology is dedicated to immunotherapy, and there's an interesting review of what the future may hold, as well as a number of articles about clinical trials of immunotherapy for allergens important to eczema, including timothy grass and cat dander. Can't wait to read the papers! --but haven't had the time.

Check this photo out. Who's this handsome fella? Yours truly, Spanish Key, Christmas 1972. My mom sent it to me recently. For me it's particularly interesting because it's really hard to see any traces of eczema on the exposed skin. There's some healing scabs on my left foot. Maybe the photographer airbrushed the shot!

There's no denying that I've had eczema as long as I can remember, so I'm interested to see a baby photo of me that looks so...normal. 

Immunotherapy: a history of histamines

"Winter" here in the San Francisco Bay Area may not be severe by anyone's standards, but there's a definite change in the air that has flipped some sort of switch for me and Voov. It's always been this way, mysterious: changing weather makes eczema worse. Toward winter, it's probably reduced humidity in the air; in spring, there's probably pollen. Can't do much about either! Slather on more moisturizer after November, maybe, but it's not a 100% remedy. And as far as antihistamines go for pollen: completely useless, in my experience.

So here we are, skin suddenly tighter and drier, the red excoriations on our hands and wrists. But neither of us is going through an extreme flare.

I ran out of Eucerin on the weekend, and picked up a jar of generic moisturizer at CVS. You know the kind. It's the store brand stuff stacked next to the Eucerin, and the price tags read "Eucerin: $15.99" "CVS Moisturizing Creme: $9.99." You get what you pay for. The problem is, the cheap stuff may LOOK the same as Eucerin, but it sucks. It's thinner and slippery and wears off fast. I have to relearn this the hard way every six months or so.

* * *

I want to share this review with you. It covers the history of our understanding of how immunotherapy works. The senior author is Mitchell Grayson, the scientist from the Medical College of Wisconsin who gave a presentation on eosinophils at the recent annual meeting of the American College of Allergy, Asthma, and Immunology.

The review is only eight pages including two of references, but it's encyclopedic. It follows immunotherapy all the way from its inception in 1911 (Leonard Noon's paper in the Lancet on injecting hay fever patients with grass pollen extract) to the current day. The authors explain how the therapy has remained essentially the same, but our understanding of how it works has evolved to become ever more complex as scientists have laid bare the secrets of the immune system.

In short: in the 1930s, scientists realized that patients given immunotherapy develop "blocking antibodies" that hinder the overeager allergic response. In the late 1960s, they learned that immunotherapy stabilizes mast cells and basophils and reduces the quantity of histamine released when patients encounter allergenic triggers. In the 1990s, after the discovery that there are at least two subtypes of helper T cells, scientists realized that immunotherapy partially shifts the T cell population in allergic patients from the allergy-related type 2 to the infection-related type 1. And in the mid-2000s, regulatory T cells were discovered; immunotherapy apparently increases the number of regulatory T cells that inhibit type 2 helper T cells.

Over time,  immunotherapy has been refined. With greater understanding of how the mucosal membranes process allergens, scientists developed sublingual immunotherapy, in which the allergens are placed under the tongue and absorbed into the tissue, where they are taken up by dendritic cells. (Straight-up oral immunotherapy, where the patient swallows the substances, is a bust.)

And, for asthma patients at risk of severe allergic reactions, doctors now administer immunotherapy along with the monoclonal anti-IgE antibody "omalizumab." Which is produced by Genentech, naturally, and costs $10,000 to $30,000 a year. I wonder, within the US, which insurance plans cover this, and whether the product is available outside the US. It's relevant to eczema because it appears to be quite effective-- it might become cheaper over time (e.g. after the patent expires) or other companies might develop alternatives to take excess IgE out of our systems.

A shared resource for immunotherapy

I'm off tomorrow to New Haven for the annual meeting of the National Association of Science Writers. A junket that will see me absent at the kids' bedtime not once, but twice, as Hidden B pointed out, using this as a cudgel to get me to change a particularly stinky diaper. So the blog will resume on Monday.

I'm pressed for time tonight, too. Have to go get some cash, pick up an organics CSA box that is contending for the status of all-time most inconvenient birthday present, make dinner, and pack. Flying into the fair city of Hartford, departing Oakland at 07:35. You may recall an earlier post in which I awarded a Mark Twain Steel Trap Award to the gentlemen responsible for the FAA's no-moisturizer-in-carryons law. Messrs. Ali, Sarwar, et al. were on my mind the other day as I purchased a small, but filthy expensive, tube of Eucerin that will see me through the next two-and-a-half days.

The eczema news of the day is a little tangential. A few posts ago, I wrote about sublingual immunotherapy. The idea in this technique is that if your eczema arises predominantly from an allergy to one thing, you try to induce your immune system to become tolerant to that thing, thereby reducing your eczema symptoms. In the past, immunotherapy doctors have injected allergens. Now, for the wimpy, there is the (slightly less effective) droplet-under-the-tongue, or "sublingual," technique. The doctor gives you a small bottle of drops and you take one or a few a day; the allergens get taken up by dendritic cells in your mucosal linings, and presented to T cells, and thus (the hope is), your body learns that the allergen is no big deal and shouldn't induce an eczema reaction.

For scientists in the realm of immunotherapy research--the study of techniques to induce tolerance in autoimmune and allergic diseases--there is now a new resource at the University of California, San Francisco. UCSF's BioShare, a bank of over 100,000 specimens from a ten-year federal project to catalog biomarkers of various diseases, is now offering its samples openly to qualified researchers. The samples were taken from patients with thoroughly diagnosed conditions, at well-defined points in the progression of the diseases. So now you can analyze the samples to see how much of this or that protein or hormone or whatever the body is producing at each point-- and how the body alters its output when immunotherapy is given. It's a way to measure whether the immunotherapy is working or not.

Have a good weekend.

Sublingual immunotherapy: why not

Interesting post today on One Mom Against Eczema. Cindy brings something called "sublingual immunotherapy" to our attention (doesn't say she's signing up for it, though).

Immunotherapy was originally done by injection. In the sublingual version, which is apparently used in some European countries, Italy in particular, a doctor (or "wellness practitioner," I suppose) puts a droplet of solubilized allergen under your tongue. You process the allergen and the idea is that your immune system, after a controlled overdosing, becomes tolerant of it--in the same way that our immune systems are generally tolerant of self-antigens.

Our bodies have the ability to become tolerant of allergens, it would appear. I am not familiar with the mechanism (time to dig out my copy of Kuby) but evidently I'm in the company of the medical profession; otherwise this type of therapy would be more successful and, you'd think, approved by the FDA.

SLIT, as those in the know call it, isn't approved by the FDA. That doesn't mean it doesn't work in some cases, or couldn't work in more cases if the dosage, formulation, etc., were optimized. (It does seem to me that SLIT would only work for you if your eczema is primarily due to one allergen.) Many FDA-approved treatments don't work or have nasty side effects. And sublingual immunotherapy, although perhaps less effective than the kind that involves a needle, does no harm to most patients (see: Hippocratic oath). Mind you, don't be the one who goes into anaphylactic shock.

So, I say, go for it, if you have the money to spare-- your insurance won't cover it in the U.S.-- and good luck. That is my attitude to eczema therapy and I've applied it to myself over the years. For example, my dad, a globe-trotting geologist, came back from Morocco with a small bottle of black cumin oil. He'd been in some street bazaar and had told a fez-wearing purveyor of unguents (see: wellness practitioner) that his son, who lived in the U.S., had always suffered from eczema. The merchant advised him that he had a guaranteed cure: "huile de nigelle," or black cumin oil. I think it's this stuff.

Read that Wikipedia entry. There's a quote from the Prophet Mohammad.

"Aisha has narrated to me that she heard the Prophet saying, 'This black seed is healing for all diseases except As-Sam.' 'Aisha said, 'What is As-Sam?' He said, 'Death.'"

It sure sounds like black cumin ought to work for eczema. (For "death" see: disease to end all diseases.)

For one week, I rubbed black cumin oil on my eczematous patches on one side, and left the other side untreated. No effect, unfortunately. It could be that it doesn't work on atheists.