By Kathleen Berger
Itching and scratching consumed Karen Berger’s life until she met dermatologist Dr. Brian Kim. The itching was debilitating for two years, deeply diminishing Karen’s quality of life. The itching started with rashes on her back, but then it spread to most areas of her body. She described the itching as unbearable, unrelenting, uncontrollable and untreatable. It never went away.
“You would scratch until you bleed. I would wake up in the morning and there would be blood on the sheets because I would scratch during the night and wasn’t even aware of it,” Karen said.
No one could diagnose the cause. Karen went to specialists, including dermatologists and allergists. She tried every test and cream they offered, but nothing worked. In fact, her condition got worse. Eventually, Karen was sent to see Dr. Kim.
Kim prescribed the anti-inflammatory drug Xeljanz, a rheumatoid arthritis medication. It’s a potential new therapy for chronic itch. While off label for itching, Karen said she didn’t have issues with insurance coverage because she has rheumatoid arthritis. It was just a matter of switching her arthritis medication to Xeljanz.
“Once I started taking it, within 24 hours the intensity of the itch started to subside,” said Karen. “Within two to three days, it was like watching it go away. And within a week, I was fairly clear. But within two weeks, I was completely clear. I was back to my normal skin then.”
Dr. Kim is an assistant professor of dermatology and co-director of the Center for the Study of Itch (CSI) at Washington University School of Medicine in St. Louis. As a researcher for the world’s first center dedicated to itch, he understands the frustration of chronic itch that doctors can’t diagnose or effectively treat. Kim is able to help Karen and some other chronic itch patients who have a type of itch from an unknown cause, a condition called idiopathic pruritus.
He said about 15% of people suffer from chronic itch, most often caused by inflammatory conditions like eczema and psoriasis, or associated with cancers and nerve disorders. Itching may accompany rashes or not. He said chronic itching without a known cause is more of a problem as people age.
“Your nervous system starts to wear out,” he explained. “That wiring gets a little bit rusty and off, and your nerves start firing in ways that they probably shouldn’t, or don’t regulate the way that they should. The other thing we also recognize is that your skin gets weaker and drier, more wrinkly and thinner. So you’re now much more susceptible to environmental insults to your skin and to the nerves that go to your skin. We also know that your immune system changes. It’s really a combination of those things that lead to some level of inflammation, your nerves going haywire, your skin barrier not being able to recover from insults that we think results in this kind of itch and why it’s so prevalent.”
As a CSI researcher, Kim and his research team had a breakthrough discovering an itch molecule. The team showed that sensory neurons in mice and people are activated by an immune signaling molecule called interleukin-4 (IL-4).
“We found a link between the immune system and the nervous system that wasn’t previously appreciated, showing that this immune molecule directly stimulates nerve cells to cause itching,” Kim said.
Further, the researchers show that IL-4 signaling can jump-start chronic itching in the setting of inflammation but also independently of pathways directly linked to inflammation. Chronic idiopathic pruritus, for example, isn’t associated with inflammation, which is why anti-inflammatory treatments, such as steroid creams, are ineffective.
Kim’s team, led by MD/PhD student and first author Landon K. Oetjen, also engineered mice to have sensory neurons that lacked the ability to respond to IL-4. When these mice were exposed to stimuli that should have made them itch, they didn’t scratch. These findings may help explain why the new drug dupilumab has had such remarkable success in improving itch in patients with eczema.
The researchers then determined that IL-4 stimulates a key protein within nerve cells- JAK1- that is a critical component of chronic itching. That finding led the team to suspect that JAK1 may be a uniquely sensitive target for multiple types of itch, even itching of unknown cause. The existing arthritis drug tofacitinib blocks this protein, so several of Kim’s patients with chronic idiopathic pruritus were given the drug.
“It’s a drug called tofacitinib, its brand name is Xeljanz. This JAK1 enzyme it blocks is known to be a great target for an anti-inflammatory agent,” he explained. “So as a result, this drug is used for rheumatoid arthritis which is an inflammatory disease of the joints.”
This led to a small study providing proof that the medication works for chronic itch patients. On average, patients in the study experienced 80% improvement. Kim said many people suffering from severe itching, who do not have rheumatoid arthritis, could not afford Xeljanz unless it’s covered by insurance for chronic itch.
“It’s very rare that a patient can get a drug like this approved. To get an on label, you’d have to do a big clinical trial and prove it’s really effective,” he explained.
In the meantime, Karen said she feels fortunate that she has her quality of life back to where it was before that first rash. She said the medication is also effective treating her arthritis.