Anyone who has to suffer the intensely unpleasant symptoms of eczema will be itching for some news of a remedy. For years, palliative treatments have brought only mild relief from the irritation eczema brings. Help, though, might at last be on its way. Scientists in California have discovered a genetic link to itching, suggesting a way forward, they say, for powerful and effective new therapies.
Collaboration between teams at the Buck Institute for Research on Aging and the University of California at Berkeley has resulted in the identification of a serotonin receptor, HTR7, as a "key mediator" of eczema and other forms of itch. Their paper is published this week in the online journal Neuron.
Eczema is the term used for a number of debilitating skin conditions that can cause intense itching sensations, dry flaky skin and a flaming red rash. According to figures from the National Eczema Association (NEA), more than 30 million Americans may have it and it affects anyone from newborns to adults. The disease can erode quality of life as dramatically as does chronic pain by causing soreness, disfigurement and immobility. As a result of the appearance of symptoms, the disease often means significant social as well as physical discomfort. As yet, eczema is incurable and treatments to manage it are often less than fully effective.
Berkeley neuroscientist Dr. Diana Bautista focuses on research of the molecular basis of the sensations of itching, touch and pain while Buck's Dr. Rachel Brem is a geneticist who studies gene regulation. Bautista, Brem and their colleagues began by looking at genes that seemed to correlate with itching in genetically distinct mouse strains.
The scientists noticed that the itchiest mice had the greatest concentration of the serotonin receptor HTR7 in the neurons that allow communication with the skin. Serotonin is a chemical in the brain that acts as a neurotransmitter, sending nerve impulses around the body including to and from the skin. It has been linked with many physical functions, including migraine, mood regulation, pain perception, appetite and sexual desire. Because abnormal serotonin signaling has long been linked to a variety of human chronic itch disorders, including eczema, the scientists knew their discovery could be important.
The researchers conducted a host of follow-up experiments that substantiated the role of HTR7 in chronic itching. They discovered that, in mice, the reduction of HTR7 led to significantly less scratching and less severe skin lesions. "We are really excited about these results," says Bautista, "the dramatic decrease in itching suggests that HTR7 may represent a new drug target for chronic itch."
Itching and scratching can also be side effects of antidepressants that can elevate levels of serotonin in the skin. In the Buck/Berkeley study, this side effect was also observed in mice — the drug Zoloft caused intense scratching, which then stopped when levels of HTR7 were lowered. It is thought, therefore, that this newly discovered gene function may well be responsible for itching in patients taking antidepressants.
In addition to eczema, Brem says, altered serotonin is linked to other forms of itch, including psoriasis and the irritation of allergic reactions. "An estimated 10 to 20 percent of the population will suffer from chronic itch at some point in their lifetime," she says. "In addition to eczema, chronic itch can stem from systemic conditions including kidney failure, cirrhosis and some cancers. Understanding the molecular basis of chronic itch is of significant clinical interest, and now there is a new target available to explore."
If you have noticed an increase in the amount you itch or you are experiencing outbreaks of rash or dry and reddened skin, it might be time to talk to your doctor about possible causes, your allergies and their treatments.
In the meantime, the NEA offers some sensible advice on looking after sensitive skin: