Clinical Rheumatology

, Volume 37, Issue 7, pp 2007–2009 | Cite as

Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade

  • Donato Rigante
  • Raffaele Manna
  • Elena Verrecchia
  • Raffaella Marrocco
  • Antonio Leone
Case Based Review


Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare autoinflammatory disorder driven by uncontrolled hypersecretion of interleukin (IL)-1, which can be clinically depicted by striking cutaneous, neurologic, and skeletal features. Little is known about the exact pathogenesis of CINCA bone disease, which mainly involves the knees. We report a 20-year-old CINCA patient, who was consecutively treated firstly with anakinra, started at 7 years, then with full dose canakinumab, started at 17 years, focusing on the typical bone abnormalities of the syndrome: the comparison of radiographs of knees performed at 7 and 20 years has shown the disappearance of a typical metaphyseal dysplasia occurring in the femurs of this CINCA patient, regularly treated with IL-1 blockade for a period of 13 years. A review of the medical literature reveals poor information on the skeletal response of CINCA syndrome to IL-1-inhibiting therapies. This contribution confirms the protean striking effects of IL-1 blockade in this peculiar autoinflammatory disorder, showing for the first time the reversal of the characteristic CINCA metaphyseal dysplasia over long-term treatment.


Anakinra Canakinumab CINCA syndrome Knee Radiography 


Compliance with ethical standards



Informed consent

A formal written informed consent was released by both patient’s parents and patient himself for the publication of this case based review.


  1. 1.
    Rigante D (2017) A systematic approach to autoinflammatory syndromes: a spelling booklet for the beginner. Expert Rev Clin Immunol 13:571–597CrossRefPubMedGoogle Scholar
  2. 2.
    Cantarini L, Lucherini OM, Frediani B, Brizi MG, Bartolomei B, Cimaz R, Galeazzi M, Rigante D (2011) Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes. Int J Immunopathol Pharmacol 24:827–836CrossRefPubMedGoogle Scholar
  3. 3.
    Rigante D (2018) A developing portrait of hereditary periodic fevers in childhood. Expert Opin Orphan Drugs 6:47–55CrossRefGoogle Scholar
  4. 4.
    Rigante D, Vitale A, Lucherini OM, Cantarini L (2014) The hereditary autoinflammatory disorders uncovered. Autoimmun Rev 13:892–900CrossRefPubMedGoogle Scholar
  5. 5.
    Rigante D (2018) New mosaic tiles in childhood hereditary autoinflammatory disorders. Immunol Lett 193:67–76CrossRefPubMedGoogle Scholar
  6. 6.
    Lopalco G, Cantarini L, Vitale A et al (2015) Interleukin-1 as a common denominator from autoinflammatory to autoimmune disorders: premises, perils, and perspectives. Mediat Inflamm 2015:194864CrossRefGoogle Scholar
  7. 7.
    Federico G, Rigante D, Pugliese AL, Ranno O, Catania S, Stabile A (2003) Etanercept induces improvement of arthropathy in chronic infantile neurological cutaneous articular (CINCA) syndrome. Scand J Rheumatol 32:312–314CrossRefPubMedGoogle Scholar
  8. 8.
    Rigante D, Ansuini V, Caldarelli M, Bertoni B, La Torraca I, Stabile A (2006) Hydrocephalus in CINCA syndrome treated with anakinra. Childs Nerv Syst 22:334–337CrossRefPubMedGoogle Scholar
  9. 9.
    Rigante D, Stabile A, Minnella A, Avallone L, Ziccardi L, Bersani G, Stifano G, Compagnone A, Falsini B (2010) Post-inflammatory retinal dystrophy in CINCA syndrome. Rheumatol Int 30:389–393CrossRefPubMedGoogle Scholar
  10. 10.
    Rigante D, Verrecchia E, Falsini B, Manna R (2016) Switch from anakinra to canakinumab in a severe case of CINCA syndrome. Int J Rheum Dis 19:1354–1356CrossRefPubMedGoogle Scholar
  11. 11.
    Cantarini L, Iacoponi F, Lucherini OM, Obici L, Brizi MG, Cimaz R, Rigante D, Benucci M, Sebastiani GD, Brucato A, Sabadini L, Simonini G, Giani T, Pasini FL, Baldari CT, Bellisai F, Valentini G, Bombardieri S, Paolazzi G, Galeazzi M (2011) Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults. Int J Immunopathol Pharmacol 24:695–702CrossRefPubMedGoogle Scholar
  12. 12.
    ter Haar NM, Annink KV, Al-Mayouf SM et al (2017) Development of the autoinflammatory disease damage index (ADDI). Ann Rheum Dis 76:821–830CrossRefPubMedGoogle Scholar
  13. 13.
    Aksentijevich I, Putnam CD, Remmers EF et al (2007) The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 56:1273–1285CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Miyamae T, Inaba Y, Nishimura G, Kikuchi M, Kishi T, Hara R, Kaneko U, Shinoki T, Imagawa T, Yokokta S (2010) Effect of anakinra on arthropathy in CINCA/NOMID syndrome. Pediatr Rheumatol Online J 8:9CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Hill SC, Namde M, Dwyer A, Poznanski A, Canna S, Goldbach-Mansky R (2007) Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA). Pediatr Radiol 37:45–52Google Scholar
  16. 16.
    Koné-Paut I, Galeotti C (2015) Current treatment recommendations for cryopyrin-associated periodic syndrome. Expert Rev Clin Immunol 11:1083–1092CrossRefPubMedGoogle Scholar
  17. 17.
    Kullenberg T, Löfqvist M, Leinonen M, Goldbach-Mansky R, Olivecrona H (2016) Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatology (Oxford) 55:1499–1506CrossRefGoogle Scholar
  18. 18.
    Sibley CH, Chioato A, Felix S, Colin L, Chakraborty A, Plass N, Rodriguez-Smith J, Brewer C, King K, Zalewski C, Kim HJ, Bishop R, Abrams K, Stone D, Chapelle D, Kost B, Snyder C, Butman JA, Wesley R, Goldbach-Mansky R (2015) A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease. Ann Rheum Dis 74:1714–1719CrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  1. 1.Institute of Pediatrics, Fondazione Policlinico Universitario A. GemelliUniversità Cattolica Sacro CuoreRomeItaly
  2. 2.Institute of Internal Medicine, Fondazione Policlinico Universitario A. GemelliUniversità Cattolica Sacro CuoreRomeItaly
  3. 3.Institute of Orthopaedics and Traumatology, Fondazione Policlinico Universitario A. GemelliUniversità Cattolica Sacro CuoreRomeItaly
  4. 4.Institute of Radiology, Fondazione Policlinico Universitario A. GemelliUniversità Cattolica Sacro CuoreRomeItaly

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