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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, …
CB and MLF contributed equally.
Handling editor Josef S Smolen
Contributors CB, DB, AC and BN collected clinical data. MLF, GIR, VB, DD and LC performed the experiments and analysed the data. CB and MLF wrote the paper. SB, YJC and BN supervised the study. All authors have read the final approval of the version published.
Funding MLF is supported by the Institut National de la Santé et de la Recherche Médicale (grant number 000427993). YJC acknowledges the European Research Council (GA 309449), and a state subsidy managed by the National Research Agency (France) under the 'Investments for the Future' programme bearing the reference ANR-10-IAHU-01. YJC and DD acknowledge the ANR (grant CE17001002).
Competing interests None declared.
Patient consent Parental/guardian obtained.
Ethics approval The study was approved by the Comité de Protection des Personnes (ID-RCB/EUDRACT: 2014-A01017-40).
Provenance and peer review Not commissioned; externally peer reviewed.