Systemic autoinflammatory syndromes

Abstract

Systemic autoinflammatory disorders (SAID) are characterized by chronic systemic or tissue inflammation, in the absence of in­fection or neoplasia. Their clinical presentation is heterogeneous and can be characterized by episodes of recurrent fever, severe systemic inflammation with macrophage activation, persistent bone or skin inflammation, among others. The study of autoinflammatory syndromes began with the description of periodic fever syndromes and the discovery of familial Mediterranean fever. Since then, more than 40 monogenic causes of SAID have been described. They can disturb different molecules that participate in the inflammatory response, resulting in constitutive activation of these molecules or failure in regulatory mechanisms. SAIDs can be classified from a clinical point of view or according to the inflammatory pathways that is predominantly dysregulated. However, both of these clas­sifications can be complex due to the heterogeneity of symptoms and dysregulated inflammatory pathways can be overlapping in the same individual. Advances in understanding inflammatory mechanisms in SAID have contributed to the identification of important therapeutic targets that are not only relevant in SAID but also in other diseases with a significant inflammatory compo­nent. The aim of this article is to discuss recent advances in the understanding of autoinflammatory diseases from a genetic point of view and the underlying mechanisms. The main inflammatory pathways involved in different clinical phenotypes of SAID and the specific therapies for each of these defects will be addressed.