PURPOSE OF REVIEW: Familial chilblain lupus belongs to the group of type I 
interferonopathies and is characterized by typical skin manifestations and acral 
ischaemia. This review aims to give an overview of clinical signs and the 
pathophysiological mechanisms.
RECENT FINDINGS: There are several mutations that can lead to this autosomal 
dominant disease. Most frequent is a mutation of the gene for TREX-1. However, 
as well cases of families with mutations in the SAMHD1 gene and, recently, with 
one for the gene that codes for the protein stimulator of interferon genes have 
been described. These genes are involved in the process of the detection of 
intracellular DNA, and their mutation results in an increased production of type 
I interferons and their gene products, resulting in auto-inflammation and 
auto-immunity. JAK inhibitors have been successfully used to treat this 
disorder. Familial chilblain is a rare disorder with very distinct clinical 
signs. Its pathophysiological mechanism gives insight into the process of 
interferon-induced inflammation in auto-immune diseases.