Hereditary periodic fever syndromes

Autoinflammatory diseases are characterized by chronic recurrent generalized inflammation without an infectious or autoimmune etiology. The rather rare genetic autoinflammatory diseases are known as hereditary periodic fever syndromes. Over the past decade, the genetic cause of most hereditary periodic fevers has been elucidated. Familial Mediterranean Fever (FMF) due to MEFV mutations, Hyper-IgD and Periodic Fever Syndrome (HIDS) due to MVK mutations, TNF Receptor Associated Periodic Syndromes (TRAPS) due to TNFRSF1A mutations, and Cryopyrin Associated Periodic Syndromes (MAPS) due to CIAS1 mutations. The phenotypic distinctions that had been defined in the past did not translate simply into the newly established genetic disease entities. The discovery of the proteins encoded by MEFV and CIAS1 led to the recognition of a novel class of intracellular proteins, involved in cytokine production and regulation of apoptosis. The insight thus gained has enabled clinical studies of apparently effective drugs in hitherto therapy-resistant disorders. As it appears, the cellbiological pathways affected in FMF and CAPS are also involved in other hereditary periodic fever syndromes and possibly even in the more common sporadic autoinflammatory diseases like systemic JIA.