Under the term of monogenic autoinflammatory syndromes are gathered a number of different conditions secondary to mutations of genes coding for proteins that play a pivotal role in the regulation of the inflammatory response. Some of them are characterized by recurrent flares of systemic inflammation presenting as sudden fever episodes associated with a dramatic elevation of acute phase reactants and with a number of clinical manifestations, such as rash, serositis (peritonitis, pleuritis), lymphadenopathy, arthritis. Familial Mediterranean Fever (FMF), Mevalonate-kinase deficiency (MKD), and Tumour necrosis factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) are the three monogenic disorders gathered under the term of hereditary recurrent fevers. In other disorders, systemic inflammation is dominated by a characteristic urticarial rash that may be associated with a number of other clinical manifestations. Familiar Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS) and Chronic Infantile Neurological Cutaneous and Articular Syndrome (CINCA) represent the clinical spectrum associated to gain-of-function mutations of a gene named NLRP3 coding for a protein called Cryopyrin. Cryopyrin is crucial for the activation and secretion of the active form of one of the most potent pro-inflammatory cytokines, interleukin (IL)-1b. A clinical phenotype similar to that observed in Familiar Cold Autoinflammatory Syndrome (FCAS2) has been observed also in patients carrying mutation of NLRP12 gene. Blau’s syndrome, includes noncaseating granulomatous inflammation affecting the joint, skin, and uveal tract and is associated with mutations of the NACHT domain of the gene CARD15 (or NOD2). Finally, other very rare disorders are dominated by the presence of sterile pyogen abscesses prevalently affecting skin, joints and bones (pyogenic disorders). This include the Pyogenic Sterile Arthritis, Pyoderma Gangrenosum and Acne (PAPA) syndrome associated to mutations of the CD2-binding protein 1 (CD2BP1) gene. Deficiency of the interleukin-1–receptor antagonist (DIRA) is the more recently identified autosomal recessive autoinflammatory syndrome. It is characterized by very severe systemic inflammation that begins around birth with multifocal osteomyelitis, periostitis, and pustulosis.
Disclosure of Interest M. Gattorno Grant/Research support from: Novartis for Eurofever, Consultant for: Novartis, Sobi, Speakers Bureau: Novartis, Sobi