Your parents were onto something: Scratching an itchy rash can indeed make it worse. We have new insights into this phenomenon thanks to a recent study that explores the relationship between scratching and inflammation in a type of eczema known as allergic contact dermatitis, using a mouse model.
Your parents were onto something: Scratching an itchy rash can indeed make it worse. We have new insights into this phenomenon thanks to a recent study published in the journal Science, which investigates how scratching exacerbates inflammation and swelling in a mouse model of a specific type of eczema known as allergic contact dermatitis.
“At first, these findings seemed to present a contradiction: If scratching an itch is harmful, why does it feel pleasurable?” said senior author Daniel Kaplan, M.D., Ph.D., a professor of dermatology and immunology at the University of Pittsburgh. “The act of scratching produces a pleasurable sensation, indicating that it must have some evolutionary benefit. Our research provides clarity by demonstrating that scratching can also serve to protect against bacterial skin infections.”
Allergic contact dermatitis is an allergic response triggered by allergens or irritants—like poison ivy or certain metals, including nickel—resulting in an itchy and swollen rash. The strong urge to scratch can lead to increased inflammation, worsening symptoms and slowing the healing process.
To uncover the factors in this damaging cycle, Kaplan, first author Andrew Liu—a student in Pitt’s Medical Scientist Training Program—and their research team used allergens that induce itch to create eczema-like symptoms in both normal mice and mice that lack itch-sensing neurons.
When the normal mice were allowed to scratch, their ears swelled and became filled with inflammatory immune cells known as neutrophils. In contrast, inflammation and swelling were significantly reduced in normal mice that were prevented from scratching by wearing small Elizabethan collars, akin to a dog’s “cone of shame,” and in those without the itch-sensing neurons. This confirmed that scratching aggravates skin inflammation.
Additionally, the researchers discovered that scratching prompts pain-sensing neurons to release a substance called substance P. This compound, in turn, activates mast cells—critical players in inflammation—that promote both itchiness and inflammation by attracting neutrophils.
“In contact dermatitis, mast cells are directly triggered by allergens, resulting in minor inflammation and itchiness,” Kaplan explained. “When we scratch, substance P further activates mast cells through a separate pathway. Thus, scratching exacerbates skin inflammation because mast cells are activated through two different mechanisms.”
Mast cells are involved in various inflammatory skin conditions and allergic responses but are also essential for defending against bacteria and other pathogens. Consequently, the researchers sought to determine if scratching-related activation of mast cells influences the skin’s microbiome.
In experiments directed by coauthor Marlies Meisel, Ph.D., an assistant professor of immunology at Pitt, the team found that scratching decreased the presence of Staphylococcus aureus, the most common bacteria responsible for skin infections.
“The discovery that scratching enhances defenses against Staphylococcus aureus indicates it might have some advantageous effects in certain situations,” noted Kaplan. “However, the harm that scratching inflicts on the skin likely exceeds this benefit, particularly in cases of chronic itching.”
The researchers are now exploring new treatment options for dermatitis and other inflammatory skin disorders such as rosacea and urticaria, focusing on therapies that reduce inflammation by targeting receptors on mast cells.
Other contributors to the study included Youran Zhang, Chien-Sin Chen, Ph.D., Tara N. Edwards, Ph.D., Torben Ramcke, M.D., Lindsay M. McKendrick, Eric S. Weiss, Jacob E. Gillis, Colin R. Laughlin, Simran K. Randhawa, Catherine M. Phelps, Kazuo Kurihara, M.D., Ph.D., Hannah M. Kang, Sydney-Lam N. Nguyen, Jiwon Kim, Tayler D. Sheahan, Ph.D., Sarah E. Ross, Ph.D., and Tina L. Sumpter, Ph.D., all associated with Pitt and UPMC; alongside Sumeyye Ozyaman from Pitt and Istanbul Medipol University.
This study received funding from the National Institutes of Health (T32NS73548, T32CA0820840, R01DK130897, U24EY035102, K99NS126569, R01AR071720, and R01AR077341) as well as the German Research Foundation.
