Here’s how dust mites give dermatitis sufferers the itch

Some eczema patients react to house dust mites digesting their skin

house dust mites, magnified

These house dust mites give eczema sufferers a nasty itch.

Gilles San Martin/Flickr (CC BY-SA 2.0)

House dust mites surround us. Burrowing cheerfully into our pillowcases, rugs and furniture, the mites feast on our dead skin cells, breaking them down into small particles they can digest.

Now that your skin is crawling, relax. If you’re like most people, you will never know they are there.

An unlucky minority, however, is very aware of dust mites. Some of these unfortunate folks have a simple dust allergy. But others have an additional condition called atopic dermatitis, often referred to as eczema. They react to the presence of dust — or rather, dust mites — with hideous itching and redness. It wasn’t totally clear what, exactly, caused people with dermatitis to react so badly to dust mites.

It turns out that these people react not to the dust mite, but to its dinner — to the breakdown products of the person’s own skin. The finding helps explain why people with atopic dermatitis react so badly to dust mites, and it provides several new options to help treat the itch. It also resolves a decade-long debate in dermatology — why people with dermatitis are scratching in the first place.

Inside out vs. outside in

Atopic dermatitis is known for producing red, cracked and dry skin and, of course, the itching. People usually get diagnosed in childhood. Sometimes it goes away as kids get older, but it still affects between 9 and 30 percent of adults in the United States.  Patients with dermatitis who react to dust are told to avoid dusty places and use special pillowcases. For the worst outbreaks, they are often prescribed a steroid cream. In some cases, they can end up in the hospital.

But what causes the itch in the first place? For the past 10 years, scientists have been scratching away at two hypotheses — one called “inside out,” and the other called “outside in.”

The “inside out” hypothesis came first, explains Graham Ogg, a dermatologist with the Medical Research Council Human Immunology Unit at the University of Oxford. The idea was that the immune system was overreacting to normal things: Dermatitis was an inside problem with the immune system itself.

In 2006, however, researchers reported in Nature Genetics that deficiencies in a protein called filaggrin were associated with atopic dermatitis. Now, it’s estimated that 20 to 30 percent of people with atopic dermatitis are also deficient in filaggrin, a protein in the outermost layer of the skin.

“It’s important for moisturizing the skin, keeping the skin hydrated,” explains Ogg. If people with dermatitis are deficient in filaggrin, then “the primary problem isn’t the immune system, it’s the barrier function in the skin.” If the barrier breaks down, more irritants can get in, prompting the immune response and the intolerable itch. So, the “outside in” hypothesis was born. In this view, the immune system wasn’t overreacting; instead it was reacting properly to the avalanche of aggravations it was faced with.

But what if these two hypotheses weren’t at odds, Ogg wondered, and instead were two sides of the same coin? To find out, Ogg and his group began by looking at a molecule called CD1a. This molecule is produced in the skin, and specializes in presenting bits of foreign matter to T cells — the immune system responders that mount attacks against foreign invaders.

It turns out that the CD1a molecules responded to extract-of-house-dust-mite — the delightful concoction that people get scratched with when they are tested for a dust allergy. And when they react, it’s because of CD1a molecules.

To find out if people with dermatitis had more CD1a than people without the condition, the scientists used suction to give eczema sufferers and healthy volunteers large blisters on their arms. The blisters were harvested for their skin and blood cells. And in patients with atopic dermatitis, those skin and blood cells were stuffed with CD1a, far more than in healthy controls.

But what was the CD1a reacting to? Usually CD1a senses fat molecules, presenting bits of them to the immune system to prep it for attack. Ogg and his group assumed that if they analyzed house dust mites, they would find the lipid or fat responsible.

Not quite. Instead, they found a protein called phospholipase A2. Phospholipase is an enzyme that dust mites produce that breaks down skin cells, producing fat molecules the mites can digest. CD1a, it turns out, responds to those lipids — reacting to the house dust mite’s dinner. Reacting, really, to the breakdown products of human skin.

This seems like support for the “inside out” hypothesis. CD1a is part of the immune system, and the immune system does seem to be over-reacting.

Filaggrin also had a role to play. The protein doesn’t just create a barrier to keep the skin moisturized — it’s also anti-inflammatory, Ogg’s group showed. If a skin sample was challenged with essence of dust mite, adding filaggrin could damp down the immune response. But eczema patients with low or no filaggrin had no defense. Their skin was more permeable, and there was nothing to stop the inflammation. The “outside in” hypothesis —the idea that the barrier function is the broken part of the system – is true too. Ogg and his colleagues report their findings February 10 in Science Translational Medicine.

“It links together the observations very nicely,” says Muzalifah Haniffa, a dermatologist at Newcastle University in England. It never was a matter of “inside out” or “outside in.” The two are inextricably linked. 

Eat like a dust mite, sting like a bee?

So, to recap: As dust mites chow down on human skin, they cause damage to the cells. People with dermatitis have immune systems that detect the products of the damage and react, causing itching and pain. Filaggrin, when present, can tamp down the response. But when absent, nothing stops the itch.

The study shows filaggrin is far more than a simple barrier protein. Instead it directly affects immune responses in the skin, something that’s never been seen before, Haniffa notes.

This isn’t the first time that Ogg’s group has come across phospholipase A2. “Bee venom also contains phospholipase. In fact it contains massive amounts,” Ogg explains. Knowing that bee venom and dust mites have something in common helps scientists to understand one of the ways that the immune system senses damage to skin — and gives them another option to consider for treatment.

Right now, clinical trials are focused on stopping the inflammatory proteins produced further down the line.  But, Haniffa says, scientists might try methods to increase the amount of filaggrin in the skin — beefing up the barrier against dust mite incursions and reducing the immune response at the same time. Other drugs or creams could target phospholipase A2, inactivating it. Without phospholipase, dust mites wouldn’t be able to break down skin cells, halting any immune reaction.

And that means we can hope for a new day. One with, hopefully, no itch.

Bethany was previously the staff writer at Science News for Students. She has a Ph.D. in physiology and pharmacology from Wake Forest University School of Medicine.

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