Neuropeptide in Blood to Help Diagnose Chronic Itch

B-type natriuretic peptide (BNP) plays a key role in chronic itch severity and can help to identify certain types of itch with a simple blood test, according to a new study led by Gil Yosipovitch, M.D., director of the Miami Itch Center, and Santosh Mishra, Ph.D., a neuroscientist and associate professor at the North Carolina State College of Veterinary Medicine.

The finding holds promise for a targeted treatment for chronic itch, which leads to more than 7 million clinic visits annually in the U.S. and is among the world’s 50 most prevalent conditions.

Leigh A. Nattkemper, Ph.D., research assistant professor of dermatology and cutaneous surgery at the Miller School, coauthored the study. Brian Kim, M.D., from the Icahn School of Medicine at Mount Sinai and Mark Hoon, Ph.D., from the National Institutes of Health, also contributed to this research.

Searching for an Itch Biomarker

Itch can be challenging to diagnose and treat because it has lacked any biomarkers, but this study may change that.

“We propose that BNP could be the first chronic itch biomarker,” said Dr. Yosipovitch, also professor of dermatology and cutaneous surgery and Stiefel Chair in Medical Dermatology at the Miller School.

New research associates BNP, which Dr. Mishra first identified as a cause of itch in mice, with chronic itch in humans. BNP and its metabolite, aminoterminal pro B-type natriuretic peptide (NT-proBNP), correlate with itch intensity. The correlation is particularly strong in patients with chronic pruritus of unknown origin, a term Dr. Yosipovitch coined in a paper published 11 years ago in the New England Journal of Medicine.

“The majority of patients with chronic pruritus of unknown origin are elderly and their itch is challenging to diagnose and treat because the cause is unknown and they do not have a primary skin rash,” Dr. Yosipovitch said. “Their lives are often miserable from the unrelenting itching and there is no targeted treatment.”

Studying BNP and NT-proBNP Levels

Researchers studied plasma BNP levels in 77 human tissue samples and an additional 33 patients with different chronic itch types. BNP and NT-proBNP levels correlated with itch severity in all patients, but patients with chronic pruritus of unknown origin were most impacted.

In an accompanying animal model study, researchers showed that increased BNP levels induced significant scratching. They also found that BNP activates the natriuretic peptide receptor A in the spinal cord. High levels of BNP can induce itch through central pathways in the spinal cord of mice, which suggests, at certain concentrations, systemic BNP may gain access to the spinal cord and stimulate central itch sensory pathways.

“It will be interesting to find the mechanism behind BNP hijacking into the central nervous system, specifically the spinal cord, in disease conditions,” Dr. Mishra said. 

Interestingly, BNP serves as biomarker for congestive heart failure, cardiac dysfunction and kidney failure.

In this study, researchers did not find an association between cardiac dysfunction and itch. The majority of patients did not have congestive heart failure, but exploring that association is an avenue for future research, according to Dr. Yosipovitch.

Dr. Yosipovitch and colleagues are conducting a study to see if reducing BNP reduces itch in humans. Those results could lead to studies with larger groups of patients to develop treatments that target the neuropeptide.