Köhlmeier-Degos disease is an interferonopathy characterized by type I and II interferon-driven inflammatory vasculopathy.

Cudrici, Cornelia D; Goel, Shubham; Sakamoto, Keiko; Jin, Seon-Pil; Sekiguchi, Akiko; Rosing, Douglas R; Huffstutler, Rebecca; Hammoud, Dima A et al. · Cell Rep Med · 2026

case_report · Level V

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Abstract

Köhlmeier-Degos disease (Degos disease [DD]) is a rare vasculopathy with characteristic skin lesions and life-threatening gastrointestinal and cerebrovascular involvement. Although DD is often viewed as a thrombo-obliterative disorder, its immunopathology remains poorly defined. Here, single-cell RNA and T cell receptor sequencing of skin, blood, and cerebrospinal fluid from DD patients reveal pervasive type I and type II interferon activation, with an interferon-γ-biased program compared with systemic lupus erythematosus. Cytotoxic CD8A<sup>+</sup> T cells show interferon-responsive activation and restricted clonotypic diversity, implicating cellular immunity in the DD inflammatory landscape. In a single-patient interventional study, JAK inhibition with ruxolitinib is associated with suppression of interferon-responsive programs, improvement of cutaneous inflammation, and stabilization of neurological disease. These findings support DD as an interferon-driven inflammatory vasculopathy and provide a rationale for further evaluation of interferon-JAK-STAT signaling. This study has been registered at ClinicalTrials.gov (NCT05998395).