Researchers at the U.S. National Institutes of Health have identified a previously underappreciated immune pathway involved in Köhlmeier-Degos disease, an extremely rare disorder that can damage blood vessels supplying the skin, brain and digestive system.
The findings suggest that the disease may be driven not only by blocked or narrowed blood vessels, but also by persistent activation of immune signals called interferons.
A disease seen in only a small number of people
Köhlmeier-Degos disease, also known as Degos disease or malignant atrophic papulosis, is exceptionally uncommon. Fewer than 200 to 300 cases have been reported in the medical literature worldwide, with estimates suggesting that fewer than 50 people may have active disease at any given time.
The systemic form can be particularly serious. When blood-vessel damage affects internal organs, patients can develop complications involving the gastrointestinal tract or central nervous system, including intestinal perforation, stroke and bleeding in the brain.
Because so few patients have been studied, researchers have had limited opportunities to understand what drives the disease.
Scientists find widespread interferon activity
In the new study, NIH researchers analyzed cells from the skin, blood and cerebrospinal fluid of patients using single-cell RNA sequencing and T-cell receptor sequencing.
The analysis found widespread activation of both type I and type II interferon pathways. The researchers also identified activated cytotoxic CD8A-positive T cells, suggesting that immune-cell activity may play a larger role in the disease than previously recognized.
The findings led the researchers to describe Degos disease as an interferon-driven inflammatory vasculopathy, opening a potential new direction for treatment research.
One patient showed a response to ruxolitinib
The researchers also conducted a proof-of-concept intervention involving one patient with systemic Degos disease.
The patient received ruxolitinib, a JAK inhibitor that interferes with cellular signaling used by interferons and other immune pathways.
Following treatment, researchers observed reduced interferon-related gene activity, improvement in active skin inflammation and stabilization of neurological disease.
The result is promising, but it does not establish ruxolitinib as a proven treatment for Degos disease. The evidence comes from a single patient, and larger studies will be needed to determine whether the approach is safe and effective across a wider group of patients.
Why the finding matters
The study gives researchers a more detailed picture of a disease that has remained difficult to study because of its extreme rarity.
Rather than focusing solely on vascular blockage, future research can investigate whether the interferon-JAK-STAT signaling pathway contributes directly to inflammation and tissue damage.
The study is registered under ClinicalTrials.gov identifier NCT05998395 and was published in Cell Reports Medicine with the DOI 10.1016/j.xcrm.2026.102947.
For patients with systemic Degos disease, the findings do not yet represent a new standard treatment. They do, however, provide a specific biological pathway that researchers can investigate in larger clinical studies.
