Unexplained chronic itch reveals unique blood biomarkers that could eventually lead to new targeted treatments

Millions of patients worldwide suffer from a chronic, itchy condition with no identifiable cause, called chronic pruritus of unknown origin (CPOI), for which there are no approved targeted therapies. Many of these patients suffer for years without much relief, but a new study from the University of Maryland School of Medicine may offer hope for future treatments. The patients were found to have lower-than-normal levels of metabolic biomarkers in their blood plasma, which could indicate a cause for their excruciating symptoms.

The results were recently published in the journal Scientific reports.

“Our study revealed a distinct deficit in certain metabolic biomarkers, including several important amino acids and other metabolites involved in immune system regulation in patients with CPUO compared to a healthy control group,” said study principal investigator Shawn Kwatra, MD, Joseph W. Burnett Professor and Chair of Dermatology at UMSOM and Chief of Dermatology at the University of Maryland Medical Center (UMMC). “This is an exciting finding because it provides new insights into the cause of this disease and identifies potential future therapeutic targets for consideration.”

Chronic pruritus of unknown origin is more common in older people and causes severe itching that lasts for more than six weeks. Current treatments used to help manage symptoms are off-label and have poor efficacy, with many patients experiencing significantly impaired quality of life.

In the latest study, Dr. Kwatra and colleagues compared blood plasma samples from CPUO patients and matched healthy control patients. They found lower levels of nine amino acids in CPUO patients compared with the control group, and that these lower levels correlated with the severity of itch.

Previous animal studies have linked low levels of these amino acids to itch symptoms in mice. These amino acids serve as building blocks for neurotransmitters, or brain chemicals, that play a role in the body’s itch response and other allergic skin reactions. Giving mice drugs such as antidepressants to boost neurotransmitters like serotonin has been shown to reduce itch symptoms.

“Many of these biomarkers that we found in reduced amounts in the blood of CPUO patients, such as tryptophan and glycine, could contribute to the underlying pathogenesis of this disease, but we certainly need larger studies to investigate this question in more detail,” Dr. Kwatra said.

The study’s co-authors also included professors from Johns Hopkins University School of Medicine and Duke University Medical Center.

In June, Dr. Kwatra published a study in JAMA Dermatology showing that a drug targeting inflammation (abrocitinib), approved to treat eczema, provided significant improvement in itch symptoms in people with CPUO as well as another itch disorder called prurigo nodularis.

He also led a study, published last year in the New England Journal of Medicinedemonstrating the efficacy of the monoclonal antibody nemolizumab in treating prurigo nodularis. The drug was approved on August 13 by the U.S. Food and Drug Administration and is one of the first FDA-approved treatments for the skin condition, which disproportionately affects African-American patients.

Dr. Kwatra serves as a consultant/advisor to several pharmaceutical companies, including the makers of abrocitinib and nemolizumab. Since assuming his position at UMSOM earlier this year, Dr. Kwatra has established the Maryland Itch Center at the University of Maryland Medical Center.