A considerable number of Americans suffer from chronic inflammatory skin conditions that lack a definitive cause and often have no effective treatments beyond symptom management. However, recent research could lead to more precise diagnostic methods and targeted therapies.
In a study published in the Nature journal Scientific Reports, researchers from the University of Maryland School of Medicine identified a new form of severe and potentially life-threatening skin disease in a male patient with erythroderma. The patient’s condition was characterized by 80% of his skin being covered with red, exfoliating lesions that itched and burned. Despite months of treatment using traditional therapies such as prednisone, anti-itch creams, and immunosuppressive drugs, the patient experienced little relief.
Study corresponding author Shawn Kwatra, MD, described how they isolated individual circulating blood cells from the patient to create a new blood test using flow cytometry. This method enabled them to identify specific cytokine signatures that were unique to this condition. The researchers received a patent for their approach involving “peripheral blood flow cytometry-based immunophenotyping,” which helped in identifying the novel skin disease.
Erythroderma is an uncommon but severe inflammatory disorder affecting most of the body’s skin surface. It causes redness and scaling that spread over the body, leading to skin peeling (sloughing) off. This can result in issues with temperature regulation and protein fluid loss, causing serious complications.
To determine which immune system components were driving the inflammatory disease, Dr. Kwatra and his team used a new flow cytometry platform technique for immunophenotyping of skin diseases for which they received a patent. They discovered that two cytokines—interleukin-13 (IL-13) and interleukin-17 (IL-17)—were at elevated levels in this patient compared to healthy controls as well as other erythroderma patients with known causes.
Following targeted treatment with biologic inhibitors of IL-13 and IL-17, the patient’s condition significantly improved. Study first author Hannah Cornman, MD, explained that “These cytokines appeared to be key in defining the disease.” Subsequently, a dual therapy using two monoclonal antibodies—dupilumab and secukinumab—led to dramatic improvements and eventual resolution of the patient’s erythroderma.
The researchers also identified the cell sources of these pathological cytokines and monitored changes in immunopathogenic (disease-causing) cells, as well as declining levels of IL-13 and IL-17 throughout the treatment course. This led to development of a new diagnostic test aimed at discovering previously unknown skin diseases and initiating appropriate treatments.
Dr. Shawn Kwatra commented that they are now exploring extending their diagnostic test to various other inflammatory skin conditions, emphasizing its potential for precision-based therapies tailored to patients’ needs.
The study was funded by the National Institutes of Health, with contributions from researchers at Duke University School of Medicine, George Washington University School of Medicine, and Johns Hopkins University School of Medicine. Mark T. Gladwin, MD—a professor and dean at the University of Maryland School of Medicine—highlighted that this research marks a significant advancement toward developing sophisticated diagnostic tools using immunophenotyping to pinpoint causes for non-specific inflammatory conditions.
