Constantly needing to scratch your skin is a hallmark of common conditions like eczema. You repeatedly feel a sudden and unwavering itch, so you scratch the affected area and feel immediate relief. But shortly thereafter, the demanding itch returns.
Where does this relentless need to scratch come from?
Isaac Chiu, a professor of Immunology at Harvard Medical School, and Liwen Deng, a postdoctoral research fellow in Chiu’s lab, said they are the first to discover that a common skin bacteria can cause the urge to scratch by acting directly on nerve cells.
“Many people experience itch,” said Chiu, senior author of the study, which was published Wednesday in the journal Cell. “This study effectively opens up this mystery of itch and potential treatment for kids and adults who have these common skin diseases.”
In conditions like eczema, which causes itchy, dry, and inflamed skin, the balance of microscopic organisms that keeps skin healthy is thrown off, allowing some to flourish. The main culprit behind itch in their study was the bacteria Staphylococcus aureus.
When the bacteria comes in contact with skin, it releases an enzyme that triggers itch by activating a protein called PAR1 on the skin’s nerve fibers. Those fibers then transmit signals from the skin to the brain, telling it to scratch the itch.
Chiu and Deng zeroed in on the reaction by exposing mice to multiple modified versions of staph and observing their scratching behavior and skin damage.
Until Chiu and Deng’s discovery, many believed that itch was sparked by skin inflammation. But the researchers’ findings suggest that the itch actually precedes skin inflammation in the itch-scratch cycle.
PAR1 is also involved in blood-clotting, so the researchers explored whether Vorapaxar, a Food and Drug Administration-approved anti-clotting oral medication that blocks PAR1, would stop itch. It did.
By treating the mice and human skin with Vorapaxar, Chiu and Deng blocked the activation of the protein, mitigating the need to scratch and minimizing skin damage.
Chiu said the drug is already being used by humans long-term and is relatively safe, but suggested its active ingredient could be reformulated and repurposed as a topical anti-itch medication.
Dr. Shawn Kwatra, a dermatology professor at the Johns Hopkins University School of Medicine who did not contribute to the study, deemed the research “one of the most fundamental studies on itch that [he has] seen in many years” because it “fills a key gap” in the understanding of the itch-scratch cycle.
“In a lot of these diseases, we see an intractable itch-scratch cycle, and the question has always been ‘Why does this happen, and what are the key drivers of it?’,” he said.
While Chiu and Deng’s work uncovered how this specific bacteria sparks the need for eczema patients to scratch, Chiu said that it is unknown whether their research relates to patients who have other skin conditions or common itchiness from other causes, like dry skin.
“Itch is still relatively mysterious in that there are many causes of itch, so we don’t know if there is [an imbalance of bacteria] in people who have dry-skin itch,” Chiu said. “Staphylococcus aureus could be present in people with those conditions and there are many conditions where [an imbalance] occurs, but we don’t know that from this study.”
Nonetheless, Kwatra said that Chiu and Deng’s discovery is “fundamental” because it introduces a new way of understanding the itch-scratch cycle, how itch can be treated, and how researchers can approach clinical trials in the future.
“Itch is the primary complaint of patients, but skin inflammation has been the endpoint in clinical trials,” said Kwatra, who is also the director of the Johns Hopkins Itch Center. “But based on this study, the endpoint of clinical trials could rather be itch.”
The findings can inform the design of oral medicines and topical creams to treat persistent itch that occurs with various conditions linked to an imbalance in the skin microbiome, such as eczema and psoriasis.
In future work, Chiu and Deng plan to explore whether other microbes can trigger itch.
“I think this research is the future for a lot of our skin diseases, because it helps trigger a new line of inquiry for what we are always searching for — the primary driver of disease,” Kwatra said.