Variant STAT4 and Response to Ruxolitinib in an Autoinflammatory Syndrome

Disabling pansclerotic morphea (DPM) is a rare inflammatory disorder characterized by fibrosis, poor wound healing, and increased mortality. In a study of four patients from unrelated families, researchers identified three novel gain-of-function variants in the gene encoding signal transducer and activator of transcription 4 (STAT4), suggesting an autosomal dominant inheritance pattern for DPM. In vitro experiments using primary skin fibroblasts showed enhanced interleukin-6 secretion and impaired wound healing, which were improved by inhibiting Janus kinase (JAK)–STAT signaling with ruxolitinib. Treatment with ruxolitinib also led to the resolution of inflammatory markers and clinical symptoms in the patients. These findings suggest that JAK inhibition may be a potential therapeutic approach for DPM.