Editorial [Autoinflammatory Disorders of Childhood: Continued Major Breakthroughs]

As a medical student in the 1970s, we were told about a mysterious entity characterized by relapsing fevers, arthritis and abdominal pain in young patients termed Familial Mediterranean Fever. Cloning of the MEFV gene on chromosome 16p13.3 in 1997 was a major step forward in our understanding of the disease. MEFV encodes pyrin, which plays a role in the regulation of the inflammasome which results in the production of pro-inflammatory cytokines, especially interleukin- 1β. Although case reports of other febrile, relapsing rheumatic related conditions in children were published, the last 5 years has represented a quantum leap in our classification, categorization and understanding of the etiopathogenesis of these disorders. There are now 9 closely related diseases, which are now temed “Autoinflammatory Diseases”. Gattorno and colleagues nicely review that these 9 diseases fall into four general categories: periodic recurrent fevers, cryopyrinopathies, granulomatous disorders and pyogeneic disorders [1]. Although quite rare, advances in this area are now moving at warp speed and investigators now are now nailing down the mutations responsible for these disorders and for the first time are able to manage them. The most exciting recent breakthroughs concern cryopyrin-associated periodic syndrome, or CAPS (not to be mistaken for catastrophic antiphospholipid syndrome). Consisting of Muckle- Wells syndrome, familial cold autoinflammatory syndrome, and neonatal onset multicystemic inflammatory disease, these reflect activation of the inflammasome via the NFκB pathway, IL-1β and caspase-1. Mutations of CIAS1 (coldinduced autoinflammatory syndrome 1) and its encoding protein, cryopyrin are thought to be responsible for massive secretion of IL-1β. CIAS1 is mainly expressed in monocytes, chrondrocytes and activated T cells. Thus, the impressive response of these patients to anakinra and no other agent except perhaps high doses of corticosteroids is a “proof of concept”. What's even more exciting is the development of more potent and effective IL-1β antagonists, which will greatly improve our patient's quality of life. REFERENCE [1] Gattorno M, Pelagatti MA, Federici S, et al. Clinical presentation of autoinflammatory syndromes in childhood, Curr Rheumatol Rev 2008; 4(1): 46-49.