The role of the NOD2/CARD15 gene in ACU is particularly intriguing: certain mutations (mainly R334W, R334Q and L469F) alter the NOD domain of the receptor, increase the activity of the NF-kB pathways and cause a rare autosomal dominant inflammatory disease, named “Blau Syndrome”, which is characterized by early-onset granulomatous arthritis, dermatitis and recurrent uveitis [7]. This evidence concerns the gene NOD2 and acquired cold urticaria.