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

Contact dermatitis, delayed allergies, and eczema

Contact dermatitis is a more important and complex factor than I thought for patients with atopic dermatitis, I learned from reading a presentation given by Dr. Luz Fonacier at the annual meeting of the American College of Allergy, Asthma and Immunology, held this year in Anaheim, CA. (I was not present at the meeting.)

Fonacier is head of the allergy section of the Division of Rheumatology, Allergy & Immunology at Winthrop University Hospital in Mineola, NY. Her talk, titled “Food Allergy and Atopic Dermatitis: Generating a Common Approach with the Dermatologist,” covered many well-known techniques to diagnose food allergy. She also devoted a large section to a controversial test: the atopy patch test.

What stood out for me was the role of contact dermatitis in atopic dermatitis. According to Fonacier, contact dermatitis, a specific type of allergic reaction to substances such as certain metals and fragrances, affects roughly two-thirds of young (infant to teenage) patients with chronic eczema. Rash and inflammation from contact dermatitis can intensify AD and change the long-term course of the disease, presumably for the worse--by exposing you to more allergens and pathogens.

While contact dermatitis often affects the hands, arms, and face, a systemic exposure to an allergen to which a person has a contact allergy can affect skin over the entire body. Metals, fragrances, and other substances that cause contact dermatitis are often present in foods. When a person eats a food containing a substance to which he or she has a contact allergy, it can manifest as a body-wide skin inflammation.

So how is this different from “classic” food allergy?

The differences lie in the timing and pathway of the reaction. “Type I” allergens such as wheat, soy, milk, and the usual culprits provoke a specific type of allergy, initiated by IgE-class antibodies, that appears over 30 minutes to two hours.

“Type IV” allergens—and I am not even sure I am using the correct term for these substances—cause a “delayed-type hypersensitivity” reaction driven by T cells that manifests hours or days later.

Nickel. You probably don't want to eat this stuff.
But it's in your cutlery and tofu.

Fonacier lists several allergens in food that can cause systemic contact dermatitis: the most common are nickel sulfate and something called “balsam of Peru,” a natural resin that contains a mixture of oils and chemicals and is used in many processed products.

Nickel is overwhelmingly found in soy and a small number of other foods, according to Fonacier’s slides. (That means that you can have a type IV allergy to soy but not necessarily test positive on a skin prick test or IgE assay.) Balsam of Peru, in contrast, is found in a wide variety of foods. Check out slide 15 of the presentation—see spices, citrus, tomatoes? I have no idea how balsam of Peru ends up in citrus peel or tomatoes; maybe it's an agriculture or food industry thing [update: Fonacier says that tomatoes contain chemicals similar to those in balsam of Peru].

Now, how to diagnose contact dermatitis? Patch testing, in which a nurse applies an array of patches containing potential allergens to a patient’s back. About two days later, an allergist looks for inflamed spots, and the corresponding patches indicate which items you should avoid.

Balsam of Peru. Appearing soon in toothpaste near you.
(And spices, and citrus, and tomatoes, and fragrances...)

Fonacier does explain patch testing in her slides, probably because it’s so obvious to an allergist. Instead, she devotes a large section of the presentation to the “atopy patch test,” or APT, which is a patch test in which the allergens are dairy, wheat, soy, and so on--those commonly assessed for type I allergies by skin prick tests and specific IgE measurements. But an APT tests for type IV hypersensitivity reactions, the delayed ones.

The advantages of the APT are that it apparently can predict type IV allergies to cow’s milk, egg, and wheat pretty well. The disadvantages are that it takes a long time and the person observing the results has to be well-trained. According to one slide, an NIAID expert panel recommends that the APT not be routinely used in the clinic because it is not as reliable as oral food challenges.

So when does Fonacier recommend using the APT? If a patient has a history of severe and persistent AD, and skin prick and IgE tests have been done, and no trigger has been identified—or if there are multiple instances of IgE reactions that have no apparent connection to AD—then it's time to try the APT.

Jon Hanifin: Barrier defects come first in eczema; allergies follow

Atopic dermatitis is a disease that arises primarily because of a breakdown in the barrier properties of the skin, and allergic reactions typical of AD are a consequence of this breakdown, Jon Hanifin told an audience last week at the annual meeting of the American Academy of Dermatology, held in San Diego.

Hanifin is one of the US's leading dermatologists, and practices at Oregon Health and Science University in Portland. He was kind enough to send me the Powerpoint of his talk, which I wanted to read because I figured from its title ("AD Pathogenesis: What's New") that it would give me a good picture of the field.

His talk was encyclopedic and technical and I'm not going to attempt to cover the whole thing. But it did make clear to me that the standard model for how eczema arises and develops is in a state of flux.

For a long time, it was thought that allergy was the dominant factor in eczema. But a key paper in 2006 linked higher risk of developing eczema and asthma to mutations in the gene coding for the protein filaggrin. Filaggrin is a long protein, consisting of a string of subunits, that has an important structural role in skin cells, especially in the uppermost layer (the stratum corneum), and also gets broken down at the surface into something called "natural moisturizing factor." From that first paper came a flood of research into filaggrin, which has helped paint a fuller picture.

One thing that jumped out at me from Hanifin's talk was that the relationship between filaggrin mutation and eczema is not simple. The severity of eczema depends on where mutations are within the protein; it's possible to have more than one mutation, which greatly increases the likelihood that you'll get eczema.

Hanifin cautions that filaggrin is not the only genetic culprit in the origins of eczema. Mutations in certain other proteins can compromise the skin barrier.

If filaggrin is messed up, your skin barrier will be too--it'll be leaky--and this means that your body gets exposed early on to a wide variety of antigens that it otherwise wouldn't be. Recently I wrote about the "hygiene hypothesis," which posits that it's good for kids to get exposed to germs because that helps prevent allergies later on, but it seems that it's not good to get exposed to too many germs, because that leads to allergies later on. There's a Goldilocks-just-right amount of germs that your immune system needs to encounter to develop properly. Hanifin laid out the current thinking, which goes as follows:

• Defects in skin cell proteins let in irritants, microbes, allergens
• This causes skin cells to release a signaling molecule called "TSLP"
• TSLP stimulates white blood cells to develop an immune system dominated by type 2 helper T cells (which act via antibodies and inflammation, rather than by macrophages that eat pathogens)
• Th2 cells induce production of IgE antibodies, and then you have classic allergies linked to eczema.

It's just a logical progression. Allergy caused by skin defects seems generally to make more sense to clinicians and researchers these days than skin defects caused by allergy.

Now, is it possible to have atopic dermatitis without abnormal IgE/Th2? Hanifin replied by email:

Yes, roughly 20% of AD patients have typical eczema without any Th2/IgE abnormalities or asthma, etc. ( I call that "pure AD" but allergists tend to call it "intrinsic.") It's been known for years and is the reason we've always doubted that allergy was causative for the skin disease--IgE is clearly involved with hay fever, food allergy and some cases of asthma that usually accompany AD.

Hanifin lays a lot of stress on the precise definition of food allergy, which is specifically defined as an adverse health effect, rather than an adverse immune response. (He refers you, and me, to the NIAID Food Allergy Guidelines.) A positive IgE test for a food doesn't necessarily mean you're allergic. You have to get ill after eating something to be truly allergic to it. Hanifin clarifies:

Not necessarily ill, but usually rapid onset of hives, maybe nausea, cough--sometimes anaphylaxis...The tests are often imprecise and not everyone with high specific IgE levels reacts to that food. Whether they have become tolerant or never were allergic can only be speculated.

My guess is that Hanifin and other dermatologists are increasingly under siege from overinformed patients such as myself who have garnered information from the internet and are now demanding that their doctors conduct allergy tests to nail down the one or two things they're convinced must be causing their eczema. In his email, he comments that there are currently "enormous financial incentives associated with the belief of allergy causation of AD." Patients, and the insurance system, are paying a lot of money for test results that aren't useful.

What I'd like to see an explanation of is why most children grow out of eczema. What is it that's happening to their skin barrier and immune systems as they mature over the ages of 3-8 or so that is freeing them from the disease? Maybe, if we knew, we could capture and intensify that process and apply it to at-risk children and adults who have remained affected.