Patients with Unexplainable Chronic Itch Have Unique Blood Biomarkers that Could Eventually Lead to New Targeted Treatments

Research Finds Low Levels of Certain Amino Acids in Blood of Patients with Chronic Itch

Millions of patients worldwide suffer from a chronic itching condition with no identifiable cause – a condition known as chronic pruritus of unknown origin (CPUO) – that has no targeted therapies approved to treat it. Many of these patients suffer for years with little relief, but a new University of Maryland School of Medicine study may provide hope for future treatments. Patients were found to have lower than normal levels of metabolite biomarkers in the blood plasma that could point to a cause of their excruciating symptoms.

Findings were published last week in the journal Scientific Reports.

“Our study found a distinct deficit in certain metabolite 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, the Joseph W. Burnett Endowed Professor and Chair of Dermatology at UMSOM and Chief of Service Dermatology at the University of Maryland Medical Center (UMMC). “This is an exciting finding because it provides novel insights into the cause of this condition and identifies potential future therapeutic targets to consider.”

Chronic pruritus of unknown origin is most prevalent among older adults and causes severe itching lasting longer than six weeks. Current therapies used to help manage symptoms are off-label and have poor efficacy, with many patients having a significantly impaired quality of life.

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

Previous animal studies have correlated low levels of these amino acids with 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. Providing mice with medications like antidepressants to boost neurotransmitters like serotonin was found to reduce itch symptoms.

“Many of these biomarkers that we found in depleted amounts in the blood of CPUO patients, like tryptophan and glycine, could contribute to the underlying pathogenesis of this condition, but we certainly need larger studies to investigate this further,” said Dr. Kwatra.

Study co-authors also included faculty 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), which is approved to treat eczema, provided significant improvement in itching symptoms in those with CPUO as well as another itching disorder called prurigo nodularis.  He also led a study, published last year in the New England Journal of Medicine, demonstrating the efficacy of the monoclonal antibody, nemolizumab, in treating prurigo nodularis. The drug was approved on August 13 by the US Food and Drug Administration and is one of the first FDA-approved treatments for this skin condition, which disproportionately affects African-American patients.

Dr. Kwatra is a consultant/advisor to several pharmaceutical companies, including the manufacturers of abrocitinib and nemolizumab.

Since beginning his position at UMSOM earlier this year, Dr. Kwatra has created the Maryland Itch Center at the University of Maryland Medical Center.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System ("University of Maryland Medicine") has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu.