Autoinflammatory diseases are characterized by dysregulation of the innate immune system. This article provides an updated overview of autoinflammatory diseases with gastrointestinal manifestations and outlines the clinical situations in which gastroenterologists should consider these conditions. The most prevalent form worldwide is familial Mediterranean fever (FMF), which is associated with mutations in the MEFV (MEditerranean FeVer) gene and presents with recurrent episodes of serositis, primarily peritonitis, accompanied by systemic inflammation. From a biological standpoint, a peripheral inflammatory syndrome is typically observed during acute attacks; however, in some cases inflammation may persist chronically. At the molecular level, these diseases involve numerous genes encoding proteins that participate in the activation or regulation of inflammatory pathways within innate immune cells.

Initially, four monogenic disorders were described FMF, TNF receptor–associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), and cryopyrin-associated periodic syndromes (CAPS) collectively referred to as the four historical autoinflammatory diseases. Each year, new monogenic autoinflammatory diseases are identified thanks to rapid advances in genetic sequencing technologies. The recent identification of somatic forms of monogenic diseases, including certain cryopyrinopathies and, in 2020, VEXAS syndrome, has added a new level of complexity to the field.