Newly Identified Pathway Explains Why Antihistamine Drugs Often Don’t Work in Eczema Patients

    By Kathleen Berger, Executive Producer for Science & Technology

    During the spring and summer, allergy sufferers take antihistamine drugs to keep allergies under control.

    Antihistamines are the standard treatment for allergies and itching, but often in the case of eczema patients with acute itch flares, the drugs don’t help.

    Dermatologist and associate professor of medicine Dr. Brian Kim, MD, is co-director of the Center for the Study of itch and Sensory Disorders at Washington University School of Medicine in St. Louis. His goal is to understand itch, which can lead to treatments and relief.  Current research is focused on helping eczema patients who suffer from debilitating itch.

    “Patients in the clinic show up and they say ‘hey, I had a terrible weekend, I went to my grandmother’s house and she has this cat and every time I go there, it just itches like crazy. And the itching is just unbearable!’,” said Kim. “We have patients say ‘when springtime comes my eczema flares terribly and I can’t really get outside, it’s so itchy.’ So we thought maybe this is the missing link. Not the rash, but it’s the itching.”

    His research shows allergens in the environment are often to blame for episodes of acute itch in eczema patients. Determined to get answers about why this happens and why antihistamines to treat allergies don’t always help, Kim became principal investigator for groundbreaking research.

    “You have antibodies circulating in your blood called IgE  (Immunoglobulin E, a substance produced by the immune system in response to allergens),” said Kim. “The thing that always bothers us about eczema is that we knew that patients with eczema have IgE against a whole host of environmental allergens, but we never knew what it did. We have traditionally attributed IgE to acting through one cell in particular. This cell is called the mast cell and these mast cells are in the skin. Well surprising is that when we modeled eczema, in the setting of eczema, the mast cells aren’t that important.”

    Kim discovered the itching doesn’t respond to antihistamines because the itch signals are being carried to the brain along a previously unrecognized pathway that current drugs don’t target.

    Kim’s observations were made in the laboratory after Kim’s team made a mouse model of eczema. Studying the animals, they found that when the mice made IgE, they began to itch. But unlike standard itch signals, in which mast cells in the skin release histamine, the IgE in mice with eczema activated a type of white blood cell called a basophil. Those cells then activated an entirely different set of nerve cells than the cells that carry itch signals that respond to antihistamines.

    “So this now starts to explain why maybe in some patients with eczema, taking antihistamines might be helpful for some of these acute itch flares,” said Kim.  “But for the majority of them it’s not helpful and it’s because it’s actually a different circuit. This really gets fundamentally at the idea – why do antihistamines not work? Why do I have acute itch flares? And why is eczema really truly an allergic disease.”

    The findings offer drug companies new targets for treating itch in eczema patients, as well as other forms of chronic itch and other conditions including hay fever, asthma, and food allergies.  The new drug targets include proteins and molecules Kim’s team identified along this newly identified neuro-immune pathway.

    Kim said if they can block this pathway with drugs, it may become a strategy for a possible new drug target.

    “So this is really the beginning. This whole field just started in the last 10 years. We used to think itch really wasn’t a symptom or even a sensation unto itself. We thought it was a mild form of pain. So this is really a new revolution. And now that we’ve uncorked the idea that not only can we target itch, there are many different forms of itch. This now just opened up a whole new way of thinking and developing drugs and going after these things. One by one, maybe multiple itches at once. “