Evidence Growing That Eczema Itch More Than Skin Deep

Emily Willingham

November 01, 2019

"My patients understand itch is transferred like nerve pain," said Gil Yosipovitch, MD, director of the Miami Itch Center and chair of the National Eczema Association scientific advisory committee.

But clinicians have argued whether atopic dermatitis is a "rash that itches" or an "itch that rashes," he acknowledged.

New evidence supports the patient-reported sensation that "eczema is the itch that rashes," Yosipovitch told Medscape Medical News.

The research, published in Nature and presented during the President's Symposium at the 28th European Academy of Dermatology and Venereology Congress in Madrid, shows that neurons serving the skin directly interact with mast cells to trigger the massive histamine release associated with atopic dermatitis inflammation.

These new findings confirm a direct role for the nervous system, which is responsible for the itchiness and was already implicated in the inflammation.

"We, as a profession, have this thinking that eczema is an immune condition, and we forget that the immune system works with nerves," Yosipovitch explained. "Ten years ago, you wouldn't accept it because there weren't any data."

"Eczema Is the Itch That Rashes"

Atopic dermatitis, a form of eczema, is far more than just itching skin. The condition cycles through flares and remissions and can take over the entire body, leading to discomfort and inflammation. In fact, the root of "eczema" is a Greek word for boiling, which is an apt description of the burning inflammation and itching people experience.

Eczema affects about one in five children, some of whom show signs of it shortly after birth. Genetic variants can increase susceptibility.

For newborns at high risk for eczema, the pre-emptive application of petroleum jelly might delay onset or limit escalation, one study suggests. However, studies on the use of cream emollients and oil baths have yielded disappointing results, as reported by Medscape Medical News.

The investigators used dust mite antigens from the skin of reactive patients to induce a reaction in mice.

The condition is so similar in mice and humans that it is difficult to distinguish samples from one another at the microscopic level, presenter Nicolas Gaudenzio, PhD, an immunologist at INSERM in Toulouse, France, told Medscape Medical News.

For their study, Gaudenzio and his colleagues used several mouse models to show that sensory neurons and immune cells work together to detect allergens related to the common dust mite.

The team pursued this research question because levels of neuropeptides — signaling molecules produced by sensory neurons called nociceptors — are elevated in people with atopic dermatitis, as are markers for mast cells.

To examine the association between neurons and mast cells, the researchers exposed mice to dust mite allergens and monitored their skin. They found that nociceptors, which transmit pain and itch messages, and mast cells do not chat with each other from a distance. Instead, they cluster together and make physical contact, with the mast cells gathering around the nociceptors like bees around a hive.

We don't really know why some people are reacting and others are not.

We don't really know why some people are reacting and others are not.

Although these neuron–mast cell units seem to be part of normal immune defense, not everyone reacts to ubiquitous dust mite allergens. In some people, "they can literally fire up the nerve fibers," he pointed out, "but we don't really know why some people are reacting and others are not. That's a black box."

Nociceptors and mast cells occur in other tissues that show an allergic response, the researchers explain, including the lungs, upper airways, and gut.

After his presentation, audience questions to Gaudenzio homed in on the same subject: Does this discovery mean new therapeutic possibilities for this sometimes-intractable condition?

That is not clear, Gaudenzio said, but the next steps will be to block the interaction between the sensory neuron and the mast cells to see if doing so forestalls the cascade of events that leads to the inflammation.

28th European Academy of Dermatology and Venereology (EADV) Congress. Presented October 12, 2019.

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