Eczema Q&A with Zimbabwean immunologist Elopy Sibanda

When developing countries appear in news stories about eczema, they mostly serve as contrast with industrialized countries, where allergic disease is on the rise. We also tend to hear only from scientists in the US, the UK, Europe, and Japan. That is why I was fascinated to read a recent story about eczema in The Herald, a government newspaper published in Harare, Zimbabwe.

The story focuses on the physical and social costs of eczema that we are so familiar with. It quotes Odwell Gwengo, founder of the Eczema Association of Zimbabwe Trust:

"Judging by the numerous cases attended to, eczema is common in our communities than we had anticipated."

Which makes you think that perhaps Western scientists have not got a complete handle on the statistics of allergic disease in the developing world. This is understandable, when HIV/AIDS, malaria, Ebola, cholera, etc., claim priority. 

The story also quoted Dr. Elopy Sibanda, a professor of clinical immunology and allergy at the University of Zimbabwe. I wrote to Dr. Sibanda with a few questions--I am well aware of my own first-wold slant--and he graciously responded to the cold call. Here's the Q&A:

Spanish Key: In the USA and elsewhere there is a perception that our societies are too clean--this is the "hygiene hypothesis"-- and that infants are not exposed to enough microbes in their early years, so that their immune systems tend toward an allergic response, and we develop eczema and asthma as a result. What is your perspective on the hygiene hypothesis?

Elopy Sibanda: I am familiar with the hygiene hypothesis but I am unsure about the extent to which it applies to our population. In immunological parlance this boils down to a Th1 to Th2 lymphocyte shift. We have seen no evidence of such a shift. The hypothesis is not an adequate explanation for the  the increase in allergic diseases. [SK comment: I'd guess in the end we will find that antibiotic overuse is to blame.]

Spanish Key: There is also a small, but vocal, anti-vaccine movement that claims that the relatively large number of vaccines given to children predisposes them to develop allergic diseases and even autism. As a result quite a few people, some of whom I have met personally, do not vaccinate their children. What is your perspective on this phenomenon?

Elopy Sibanda: There are pockets of religious sects that are against the immunization of children for various reasons. Immunization rates in Zimbabwe are quite high. I have not seen any convincing evidence of immunization influencing allergic trends. The anti-vaccine advocates just have to provide us with the evidence. [SK comment: I would love to see Dr. Sibanda in conversation with a Marin County anti-vaccine advocate.]

Spanish Key: I have read that eczema may be an evolutionary development to protect the body against helminthic worms. What is your opinion?

Elopy Sibanda: My experience is that  people with eczema are at no lesser risk of helminthic infections than those without. If it was developed for that purpose it is failing in its role. [SK comment: very interesting. I wonder why eczema has persisted in our DNA despite being so debilitating in some cases, if it does not have some hidden benefit. But then look at all the other hereditary diseases we are passing along to our children--diabetes, Tay-Sachs, Huntington's, multiple sclerosis, etc.]

Spanish Key: What do you think are the most important therapies that African children and adults with eczema lack?

Elopy Sibanda: Before we can address the issue of therapies, the challenge we face is patient education and disease awareness. Once the people understand the disease, they will begin to appreciate the interventions and establish treatment options and priorities. Like everywhere in the world medical interventions aim to stop the itch (anti-histamines), reduce the dryness (mosturisers and ointments) and prevent infection. [SK comment: very similar to the NEA's outlook here in the US. Although antihistamines generally not considered useful for treating itch of chronic eczema, as I have discussed in earlier blog posts.]

I am grateful to Dr Sibanda for replying and I hope to add other voices to this blog to build a truly global perspective on eczema.

Filaggrin mutations cause distinct pattern of eczema in children

The giant protein filaggrin has several vital functions in skin. People with mutated copies of the filaggrin gene (FLG) are at risk of developing eczema that begins earlier and is more severe than usual. A new population study by Danish scientists (published in the journal PLoS ONE) now shows that children with FLG mutations develop a distinct variety of eczema, with emphasis on exposed areas such as the cheeks and the backs of the hands.

The research, led by Hans Bisgaard at the University of Copenhagen, could in the future help doctors diagnose children at risk of developing eczema and design personalized treatment for them—including therapy that could change the course of the disease.

The researchers analyzed data from the Copenhagen Study on Asthma in Childhood, which comprised 411 children born to mothers with asthma and followed them over the course of seven years, with checkups every six months (or more often, if eczema flares warranted). The scientists tested DNA from the children, checking to see if they had one of the two most common FLG mutations, known as R501X and 2282del4.

The results were not as cleancut as one might like. Roughly 15% of the 170 children who developed eczema had FLG mutations. But so did 7% of the 212 children who did not develop eczema. So clearly having mutated FLG does not guarantee eczema, and there are other factors at work to compensate for the mutation or cause disease to develop even if you have good filaggrin.

The researchers found that, in general, short- and long-term symptoms of eczema were worse in children with mutated FLG; and the disease set in earlier and flares tended to cluster in certain areas, most importantly  the cheeks and backs of the hands.

What is your child’s eczema like? Or what was yours like as a child? Does it fit this pattern? I seem to remember it concentrated on the backs of my knees and the insides of my elbows. But over the years it has moved around a lot. Maybe we will see scientists develop a catalog of eczema subtypes caused by known mutations.

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.

"Do not scratch your itch. Ever."

When characters like Donald Trump set the standard on Twitter it's hard to get worked up about any single tweet in particular.

Nonetheless, yesterday a tweet in my feed got me riled.

Claudia Aguirre is scientific communications manager at Dermalogica, a skincare/cosmetics company headquartered in California.

The tweet apparently came from an audience member in a talk Aguirre was giving in Antwerp, Belgium. [update: via Twitter, Aguirre implied that I took her words out of context, since she says the talk was not about eczema.]

Aguirre has tweeted the "don't scratch"/eczema message a couple times that I've seen, so my conclusion is that she believes it.

For the record, Aguirre does understand that eczema is a complex problem with many causes and treatments. If you like 17-minute YouTube videos, she's got one for you.

But “don't scratch”? That would be nice. I've spent my whole life trying to pull that off. 

With my customary tact, I made my opinion known. Aguirre replied. My man Gary beat me to the punch.

The problem: you can TELL someone not to scratch, but it doesn't work. It’s not that you won’t stop, it’s that you can’t stop. Google "eczema don't scratch" and the results fall into two main categories: pages advising you not to scratch your eczema, and pages from outraged eczema patients and parents saying that this is bullshit. (See this recent discussion on the NEA forum.)

Not only does it not work, telling people to stop scratching makes them feel bad. They already suffer from the itch, sores, and shame of eczema; now you’re telling them they don’t have any self-control. They then believe it’s their fault they look and feel the way they do.

The urge to itch in cases of extreme eczema is so intense that willpower is no defense. Not to mention that willpower is irrelevant while you're asleep, which is when many patients scratch.The intensity of eczema itch is hard to believe. I know, because I and my daughter have eczema, and when she’s itchy and I’m not, I can hardly understand what she’s going through. But when I’m itchy, it’s like a demon has possessed me, like Linda Blair’s character in The Exorcist.

So is it possible to exorcise the demon?

• Topical steroids give you some control, but not many people would claim they are the answer.
• Yoga and meditation: meh.
• Keeping your hands busy with art or a musical instrument might work  as long as you keep doing that activity. Once you stop, the itch starts.
• I am aware of a handful of psychiatric techniques, including habit reversal, made popular by Christopher Bridgett in the UK. I like habit reversal, and believe that it works to reduce habitual, nervous scratching—and thereby calm the itch/scratch cycle and bring overall relief to a degree. But it’s not a solution for everyone. It takes work, and commitment, and for some people, habitual scratching is not the dominant factor in their eczema. (E.g. I get eczema on my face which is caused by pollen. I get outbreaks caused by weather, exercise, food triggers, dust mites, animal dander and stress.)

Dr. Aguirre, you say it’s possible for eczema patients to stop scratching. Would you mind telling us how?

Antibody therapy for extreme eczema

I just wrote a short post on the NEA website about the use of omalizumab, an anti-IgE antibody, as an experimental therapy for patients with refractory (hard-to-treat) eczema. Omalizumab is currently approved in the US for treating extreme asthma--it knocks IgE levels down and thereby reduces the immune system's tendency to flare up. It appears to work for around 20% of eczema patients, but the current evidence is pretty slim so I'd wait a few years before calling it a real therapy.