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The type I interferonopathies, Mendelian disorders characterised by constitutive upregulation of the type I interferon (IFN) pathway, are associated with a spectrum of phenotypes particularly involving the brain and the skin.1 Mutations in the 3′−5′ DNA exonuclease TREX1 were the first described cause of the severe encephalopathy Aicardi-Goutières syndrome (AGS),2 of which acral vasculitic lesions are a well-recognised feature. Familial chilblain lupus (FCL) is the name given where such lesions occur in the absence of neurological disease.3 TREX1 dysfunction, due to biallelic loss of function or dominant negative heterozygous mutations, is postulated to lead to aberrant immune recognition of self-nucleic acids inducing the production of type I IFNs. These potent cytokines drive the expression of IFN-stimulated genes (ISGs) through the engagement of a common receptor and the subsequent activation of Janus kinase 1 (JAK1) and tyrosine kinase 2. We describe, to our knowledge for the first time, the efficacy of the JAK1/2 inhibitor ruxolitinib in a patient with TREX1-related skin disease. Parental consent was obtained for the use of ruxolitinib on a compassionate basis.
The patient carried a previously recorded dominant negative heterozygous mutation in TREX1 (c.52G>A, …
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