Artículo Médico

Artículo Médico
Ciencias de la Salud I
Integrantes:
* Arias Carrera Grover
* Cordova Tapia Holkan Emmanuel
* García Beltrán Diego
* López Soto Iris Itzel
* Arias Carrera Grover
* Cordova Tapia Holkan Emmanuel
* García Beltrán Diego
* López Soto Iris Itzel

ORIGINAL ARTICLE
Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1β InhibitionRaphaela Goldbach-Mansky, M.D., Natalie J. Dailey, M.D., Scott W. Canna, M.D., Ana Gelabert, M.S.N., Janet Jones, B.S.N., Benjamin I. Rubin, M.D., H. Jeffrey Kim, M.D., Carmen Brewer, Ph.D., Christopher Zalewski, M.A., Edythe Wiggs, Ph.D., Suvimol Hill, M.D., Maria L. Turner, M.D., Barbara I. Karp, M.D., Ivona Aksentijevich, M.D., Frank Pucino, Pharm.D., Scott R. Penzak, Pharm.D., Margje H.Haverkamp, M.D., Leonard Stein, M.D., Barbara S. Adams, M.D., Terry L. Moore, M.D., Robert C. Fuhlbrigge, M.D., Ph.D., Bracha Shaham, M.D., James N. Jarvis, M.D., Kathleen O'Neil, M.D., Richard K. Vehe, M.D., Laurie O. Beitz, M.D., Gregory Gardner, M.D., William P. Hannan, M.D., Robert W. Warren, M.D., Ph.D., William Horn, M.D., Joe L. Cole, M.D., Scott M. Paul, M.D., Philip N. Hawkins, M.D., TuyetHang Pham, B.S., Christopher Snyder, B.S., Robert A. Wesley, Ph.D., Steven C. Hoffmann, M.S., Steven M. Holland, M.D., John A. Butman, M.D., Ph.D., and Daniel L. Kastner, M.D., Ph.D.
N Engl J Med 2006; 355:581-592August 10, 2006DOI: 10.1056/NEJMoa055137
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Abstract
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Citing Articles (243)
Neonatal-onset multisystem inflammatory disease (NOMID), also known as chronicinfantile neurologic cutaneous articular (CINCA) syndrome, is a rare chronic inflammatory disease.1,2 An urticaria-like rash develops within the first six weeks of life, and a characteristic bony overgrowth predominantly involving the knees develops in most affected children. Central nervous system (CNS) manifestations include chronic aseptic meningitis, increased intracranial pressure, cerebralatrophy, ventriculomegaly, and chronic papilledema, with associated optic-nerve atrophy and loss of vision, mental retardation, seizures, and sensorineural hearing loss. Other manifestations include short stature, hepatosplenomegaly, leukocytosis, and an elevation in serum levels of amyloid A and C-reactive protein and in the erythrocyte sedimentation rate. Therapies are aimed at suppressinginflammation and have included high-dose corticosteroids, disease-modifying antirheumatic drugs, and biologic agents targeting tumor necrosis factor (TNF). Although these medications are moderately effective, inflammation persists in most children, and a 20 percent mortality rate has been reported before adulthood.3
The discovery of the genetic basis of neonatal-onset multisystem inflammatory disease4,5has led to the inclusion of this syndrome in a group of hereditary systemic autoinflammatory disorders.6 Mutations in the gene for the cold-induced autoinflammatory syndrome 1 (CIAS1), mostly newly occurring ones, are present in about 60 percent of children who receive a clinical diagnosis of the disease. Patients with and those without CIAS1 mutations have similar disease phenotypes.5 CIAS1mutations were initially identified in two phenotypically milder familial syndromes,7 familial cold autoinflammatory syndrome2 and the Muckle–Wells syndrome.2 Both disorders are characterized by episodes of urticarial rash and systemic inflammation but not bony overgrowth, chronic meningitis, or mental retardation.
CIAS1 encodes cryopyrin (also known as NALP3),8 which belongs to a group of interactingproteins that form a macromolecular complex termed the “inflammasome.”8 Inflammasome assembly leads to the activation of caspase 1, which cleaves pro–interleukin-1β into its bioactive form (Figure 1 in the Supplementary Appendix, available with the full text of this article at www.nejm.org). There is conflicting evidence as to whether cryopyrin activates nuclear factor-κB (NF-κB), another...