Researchers at Washington University School of Medicine in St. Louis have found that allergens in the environment can cause episodes of acute pruritus in eczema patients. Further, the itching can fail to respond to antihistamines because the itch signals are being carried to the brain along a previously unrecognized pathway not targeted by current treatments.
In the study published online ahead of print in the journal Cell (Jan. 6, 2021), the investigators suggest the findings could point to a possible new treatment target and strategy for eczema patients with episodes of acute itch.
“We used to think that itch and pain were carried along the same subway lines in the nerves to the brain, but it turned out they were not, and these new findings show there is another pathway entirely that is causing these episodes of acute itching in eczema patients,” said Dr. Brian S. Kim, the study’s principal investigator, in a press release. Dr. Kim is a dermatologist and an associate professor of medicine in the Division of Dermatology at the Department of Medicine at the Washington University School of Medicine.
“The itch can be maddening. Patients may rate their chronic itch at around a 5 on a scale of 10, but that goes up to 10 during acute itch flares,” Dr. Kim added. “Now that we know those acute flares are being transmitted in an entirely different way, we can target that pathway, and maybe we can help those patients.”
The typical pathway for itching in eczema patients involves cells in the skin that are activated and then release histamine, which can be treated with antihistamine therapies.
However, with acute itching, a different type of cell in the bloodstream transmits itch signals to the nerves. Those cells produce too much of another non-histamine substance that triggers itch; therefore, antihistamines do not work in response to such signals.
“We have connected acute itching in eczema to allergic reactions transmitted by an entirely different population of cells,” said Dr. Kim, who is also the co-director of the Center for the Study of Itch & Sensory Disorders at the Washington University School of Medicine. “In patients who experience episodes of acute itching, their bodies react in the same way as in people with acute allergy. If we can block this pathway with [proper treatments], it might represent a strategy for treating not only itch but other problems, including perhaps hay fever and asthma.”
There have been several clinical studies conducted to test a strategy that involves blocking Immunoglobulin E (IgE), a substance produced by the immune system in response to allergens. Patients with allergies produce IgE, causing allergic reactions, but its role in itch has been unclear.
Dr. Kim and his team of researchers reviewed data from clinical studies of treatments aimed at treating chronic itching. The investigators found a pattern in which patients reported episodes of acute itching, often after exposure to environmental allergens. The study’s authors also found that eczema patients who make IgE in response to allergens in the environment were more likely to experience those episodes of severe, acute itch.
“Environmental allergens actually promote this type of itch,” Dr. Kim explained. “Say a patient with eczema goes to grandma’s house, where there is a cat, and that person’s itching just goes crazy. It is likely cat dander is activating IgE, and IgE is activating itch.”
The study’s investigators took these observations to the laboratory, where they made a mouse model of eczema. Studying the animals, researchers found that when the mice made IgE, they began to itch. But unlike standard itch signals, in which mast cells release histamine, the IgE in mice with eczema activated the white blood cell, basophil. Those cells then activated an entirely different set of nerve cells than the cells that carry itch signals that respond to antihistamines. The discovery that acute itching in eczema is linked to exposure to allergens may guide patients to avoid triggers that make them itch intensely, including animals, dust, mould or certain foods. According to the study’s authors, the finding could also offer pharmaceutical companies new targets for treating itch in eczema patients, including proteins and molecules that were identified along this newly identified neuro-immune pathway.