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A Vaccine against Poison Ivy Misery Is in the Works as Scientists Also Explore New Treatment Paths - Scientific American
Eleven summers ago I moved into a small house surrounded by woods but with enough sunshine to indulge my gardening habit. It was my own little Eden, complete, as it turned out, with a botanical snake in the garden: poison ivy. I learned to avoid its red shoots of spring, waxy green triad of leaves in summer, crimson foliage of autumn, and hairy vines still lurking in winter. I wore gloves to weed and sow, but still I'd wind up with the devilishly itchy rash a few times a year, lasting three weeks at a stretch. Every year 10 million to 50 million Americans share my woes. According to some older studies, poison ivy and its cousins poison oak and poison sumac cause 10 percent of lost-time injuries among U.S. Forest Service workers and lead one third of them in California, Oregon and Washington to miss work during fire seasons. To make matters worse, the climate crisis is turning poison ivy more toxic and expanding its range. A six-year study conducted at Duke University in the early 2000s found that elevated levels of carbon dioxide, a driver of climate change, induce the plant to produce a more allergenic form of urushiol, the oily resin responsible for the rash. Given the toll in suffering and dollars, you would think serious attention would be paid to this worsening public health issue. You'd be wrong. “This condition is really underappreciated,” observes biochemist Sven-Eric Jordt, whose lab at Duke investigates pain and itch mechanisms. Contact dermatitis from poison ivy is usually treated by local doctors, not in big research centers, he says. And pharma companies see more profit in developing drugs for chronic skin condittions such as eczema than for an ephemeral rash. Jordt is one of a handful of scientists who take this nemesis seriously, and I am happy to report that they have made progress. Among recent discoveries: surprising pathways that cause the itchy rash, new targets for treatment and—be still, my heart—a vaccine in development that aims to prevent the urushiol reaction. If you Google poison ivy, you will get a torrent of treatment advice such as to take antihistamines and apply cortisone cream. Neither does much good. (Cortisone pills do help if given early and in sufficient doses.) Why not? Animal studies indicate that the response to urushiol has nothing to do with histamines—bodily chemicals involved in many allergic reactions—so antihistamines are useless. Working with urushiol-exposed mice, Jordt and his colleagues found that an immune chemical called interleukin 33 (IL-33) plays a key role in causing the infernal itch. Released by skin cells, it acts directly on sensory neurons in the skin. If either IL-33 or its receptor is blocked, the mice stop scratching—a finding that suggests a new route for treatment. Because IL-33 is involved in asthma and eczema, at least two companies already are working on drugs to block it, but its role in poison ivy was a surprise. Dermatologist Brian Kim, co-director of the Center for the Study of Itch & Sensory Disorders at Washington University in St. Louis, has identified a second, nonhistamine pathway involved in poison ivy rashes. Also working with mice, Kim, along with scientists at Johns Hopkins University, has shown that immune system components called mast cells trigger itch neurons in the skin. The mast-cell and IL-33 pathways are both “very new mechanisms,” Kim says. In the past, dermatologists believed that urushiol rashes and itch were triggered by the immune system's T cells, which rally antibodies to attack the skin irritant. Kim believes that T cells do cause the inflamed rash of poison ivy but that these other pathways provoke the itch: “In other words, what causes the itch is very different from what causes the rash.” Both recently discovered mechanisms present new targets for treatment, but first scientists need to extend the work in humans. Jordt says it's been difficult to attract study funding and to obtain tissue samples from poison ivy patients. Human research is proceeding with a compound called PDC-APB, which would be injected as a vaccine once every year or two to prevent poison ivy misery. Developed at the University of Mississippi, it is a synthetic version of urushiol's active component. “We believe the shot will lead to desensitization and reduce or eliminate reactions to poison ivy, oak and sumac,” says Ray Hage, CEO of Hapten Sciences, which has licensed the compound. It works well in guinea pigs (I've seen photos), passed initial safety testing in humans and is about to be evaluated in a small randomized controlled trial . People are beating down the door to try the vaccine, Hage reports: “Every March I start to get e-mails from people asking, ‘Where is the drug? Can I be in a trial?’” My feelings exactly. .
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