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: Raphaela Goldbach-Mansky
• Journal: Current rheumatology reports (Curr Rheumatol Rep) Vol. 13 Issue 2 Pg. 123-31 (Apr 2011) ISSN: 1534-6307 [Electronic] United States
• PMID: 21538043 (Publication Type: Journal Article, Review)

Chemical References

• Antirheumatic Agents
• Carrier Proteins
• Inflammasomes
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human

Topics

• Adolescent
• Animals
• Antirheumatic Agents (therapeutic use)
• Carrier Proteins (genetics)
• Child
• Cryopyrin-Associated Periodic Syndromes (drug therapy, genetics, pathology)
• Drug Evaluation, Preclinical
• Humans
• Infant, Newborn
• Infant, Newborn, Diseases (drug therapy, genetics, pathology)
• Inflammasomes (drug effects)
• Interleukin 1 Receptor Antagonist Protein (therapeutic use)
• Interleukin-1beta (antagonists & inhibitors, metabolism)
• Mutation
• NLR Family, Pyrin Domain-Containing 3 Protein
• Syndrome