title: Current status of understanding the pathogenesis and management of patients with NOMID/CINCA.
abstract: Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, and arthritis (CINCA) syndrome is the most severe clinical phenotype in the spectrum of cryopyrin- (NLRP3/NALP3) associated periodic syndromes (CAPS). The study of patients with NOMID/CINCA has been instrumental in characterizing the extent of organ-specific inflammatory manifestations and damage that can occur with chronic interleukin (IL)-1β overproduction. Mutations in CIAS1/NLRP3 lead to constitutive activation of the "NLRP3 inflammasome," an intracellular platform that processes and secretes increased amounts of IL-1β. The pivotal role of IL-1β in NOMID/CINCA has been demonstrated in several clinical studies using IL-1--blocking agents that lead to rapid resolution of the inflammatory disease manifestations. NOMID/CINCA is a monogenic autoinflammatory syndrome; and the discovery of the role of IL-1 in NOMID has led to the exploration in the role of IL-1 in other disorders including gout and Type II diabetes. The inflammation in NOMID/CINCA is continuous with intermittent flares, and organ manifestations encompus the central nervous system, eye, inner ear, and bones. This review discusses updates on the pathogenesis of NOMID/CAPS, emerging long term-outcome data regarding IL-1--blocking agents that have influenced our considerations for optimal treatment, and a monitoring approach tailored to the patient's disease severity and organ manifestations.
authors.affiliation: Translational Autoinflammatory Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health, Building 10, Room 6D-47B, 10 Center Drive, Bethesda, MD 20892, USA. goldbacr@mail.nih.gov
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
mesh_terms: D000293:Adolescent; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D058847:Inflammasomes / Q000187:drug effects; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D013577:Syndrome
chemical_list: D018501:Antirheumatic Agents; D002352:Carrier Proteins; D058847:Inflammasomes; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human