Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA)
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Neonatal onset multisystem inflammatory disease (NOMID), an autoinflammatory disease, is characterized by fever, chronic urticarial rash, CNS manifestations, and arthropathy. Approximately 50% of patients with NOMID have de novo missense mutations in CIAS1, which is associated with modulation of the IL-1b and apoptotic pathways. Approximately 60% of NOMID patients have prominent arthropathy, most commonly involving the knees, the cause of which remains poorly understood.
To more fully describe the findings of NOMID arthropathy on MRI and radiography and to provide a better understanding of the origin of the bony lesions.
Materials and methods
We imaged 20 patients with NOMID to further investigate NOMID-associated bony lesions.
Bony abnormalities were seen in the knees of 11/20 patients. The knee findings included enlarged, deformed femora and patellae in all and tibiae in the majority, without evidence of synovitis. Some patients had other joint involvement. Most had short stature and valgus or varus knee deformities. No association was noted between bony abnormalities and CIAS1 mutations. The abnormalities appeared to be the result of a mass-producing process. The resulting heterogeneously calcified masses appeared to originate in the physis and deformed the adjacent metaphysis and epiphysis.
These findings suggest that the arthropathy of NOMID is the result of abnormal endochondral bone growth. Further investigation is needed to determine whether this deformity is triggered by inflammation early in development or by CIAS1 mutations causing abnormal chondrocyte apoptosis.
- Lorber J (1973) Syndrome for diagnosis: dwarfing, persistently open fontanelle; recurrent meningitis; recurrent subdural effusions with temporary alternate-sided hemiplegia; high-tone deafness; visual defect with pseudopapilloedema; slowing intellectual development; recurrent acute polyarthritis; erythema marginatum, splenomegaly and iron-resistant hypochromic anaemia. Proc R Soc Med 66:1070–1071
- Prieur AM (2001) A recently recognised chronic inflammatory disease of early onset characterised by the triad of rash, central nervous system involvement and arthropathy. Clin Exp Rheumatol 19:103–106
- Hull KM, Shoham N, Chae JJ et al (2003) The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol 15:61–69 CrossRef
- Leone V, Presani G, Perticarari S et al (2003) Chronic infantile neurological cutaneous articular syndrome: CD10 over-expression in neutrophils is a possible key to the pathogenesis of the disease. Eur J Pediatr 162:669–673 CrossRef
- Stojanov S, Kastner DL (2005) Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol 17:586–599 CrossRef
- Aksentijevich I, Nowak M, Mallah M et al (2002) De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 46:3340–3348 CrossRef
- Feldmann J, Prieur AM, Quartier P et al (2002) Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet 7:198–203 CrossRef
- Hoffman HM, Mueller JL, Broide DH et al (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 29:301–305 CrossRef
- Torbiak RP, Dent PB, Cockshott WP (1989) NOMID – a neonatal syndrome of multisystem inflammation. Skeletal Radiol 18:359–364 CrossRef
- Kaufman RA, Lovell DJ (1986) Infantile-onset multisystem inflammatory disease: radiologic findings. Radiology 160:741–746
- DeCunto C, Liberatore D, San Roman J et al (1997) Infantile-onset multisystem inflammatory disease: a differential diagnosis of systemic juvenile rheumatoid arthritis. J Pediatr 130:513–515
- Ballock RT, O’Keefe RJ (2003) Physiology and pathophysiology of the growth plate. Birth Defects Res C Embryo Today 69:123–143 CrossRef
- Masumoto J, Dowds TA, Schaner P et al (2003) ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis. Biochem Biophys Res Commun 303:69–73 CrossRef
- Dowds TA, Masumoto J, Zhu L et al (2004) Cryopyrin-induced interleukin 1beta secretion in monocytic cells: enhanced activity of disease-associated mutants and requirement for ASC. J Biol Chem 279:21924–21928 CrossRef
- Yarom A, Rennebohm RM, Levinson JE (1985) Infantile multisystem inflammatory disease: a specific syndrome? J Pediatr 106:390–396 CrossRef
- Shumate ML, Yumet G, Ahmed TA et al (2005) Interleukin-1 inhibits the induction of insulin-like growth factor-I by growth hormone in CWSV-1 hepatocytes. Am J Physiol Gastrointest Liver Physiol 289:G227–G239 CrossRef
- Martensson K, Chrysis D, Savendahl L (2004) Interleukin-1beta and TNF-alpha act in synergy to inhibit longitudinal growth in fetal rat metatarsal bones. J Bone Miner Res 19:1805–1812 CrossRef
- Dinarello CA (1991) Interleukin-1 and interleukin-1 antagonism. Blood 77:1627–1652
- Hashkes PJ, Lovell DJ (1997) Recognition of infantile-onset multisystem inflammatory disease as a unique entity. J Pediatr 130:513–515
- Frenkel J, Wulffraat NM, Kuis W (2004) Anakinra in mutation-negative NOMID/CINCA syndrome: comment on the articles by Hawkins et al and Hoffman and Patel. Arthritis Rheum 50:3738–3739; author reply 3739–3740 CrossRef
- Lovell DJ, Bowyer SL, Solinger AM (2005) Interleukin-1 blockade by anakinra improves clinical symptoms in patients with neonatal-onset multisystem inflammatory disease. Arthritis Rheum 52:1283–1286 CrossRef
- Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA)
Volume 37, Issue 2 , pp 145-152
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Diagnostic Radiology, National Institutes of Health (NIH), Warren G. Magnuson Clinical Center, 10 Center Drive, Rm # N242, Bethesda, MD, 20892, USA
- 2. National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD, USA
- 3. Department of Radiology, Medical Imaging, Children’s Memorial Hospital, Northwestern University, Chicago, IL, USA