The mechanisms behind acute itch flare-ups and why antihistamine drugs often don’t work to control them are explained in a paper published in Cell yesterday.
According to a team from Washington University School of Medicine in St. Louis, allergens in the environment often are to blame for episodes of acute itch in eczema patients, and the itching often 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. "Years ago, 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 weren't, and these new findings show there's another pathway entirely that's causing these episodes of acute itching in eczema patients," said principal investigator Brian S. Kim.
The typical pathway for itching in eczema patients involves cells in the skin that are activated and then release histamine, which can be inhibited with antihistamine drugs. But with this 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 don't work in response to such signals.
In recent years, several clinical studies have tested a strategy that involves blocking Immunoglobulin E (IgE). Patients with allergies produce IgE, causing allergic reactions, but its role in itch has been unclear. Reviewing data from clinical studies of drugs aimed at treating chronic itching, Kim found a pattern in which patients reported episodes of acute itching, often after exposure to environmental allergens. He 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.
Kim's team took these observations to the laboratory, where his 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 release histamine, the IgE in mice with eczema activated basophils. Those cells then activated an entirely different set of nerve cells than the cells that carry itch signals that respond to antihistamines.