Enterocolitis Followed by Recurrent Sepsis-Like Episodes

  • Tania Siahanidou
  • Sofia Tantou
  • Maria Kanariou


Autoinflammatory diseases should be included in the differential diagnosis of recurrent episodes of systemic inflammation, as early as in the neonatal age

NLRC4 mutations can cause life threatening macrophage activation syndrome

Early DNA analysis and identification of the responsible gene is crucial for early diagnosis in order to decide the most appropriate therapy and improve patients prognosis


NLRC4 Inflammasome IL-1β Whole exome sequencing 


  1. 1.
    Siahanidou T, Koutsounaki E, Skiathitou AV, Stefanaki K, Marinos E, Panajiotou I, Chouliaras G. Extraintestinal manifestations in an infant with microvillus inclusion disease: complications or features of the disease? Eur J Pediatr. 2013;172(9):1271–5.CrossRefGoogle Scholar
  2. 2.
    Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Puck JM, Sullivan KE, Tang ML, Franco JL, Gaspar HB. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35(8):696–726.CrossRefGoogle Scholar
  3. 3.
    Corridoni D, Arseneau KO, Cominelli F. Functional defects in NOD2 signaling in experimental and human Crohn disease. Gut Microbes. 2014;5(3):340–4.CrossRefGoogle Scholar
  4. 4.
    Man SM, Kanneganti TD. Regulation of inflammasome activation. Immunol Rev. 2015;265(1):6–21.CrossRefGoogle Scholar
  5. 5.
    Romberg N, Al Moussawi K, Nelson-Williams C, Stiegler AL, Loring E, Choi M, Overton J, Meffre E, Khokha MK, Huttner AJ, West B, Podoltsev NA, Boggon TJ, Kazmierczak BI, Lifton RP. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat Genet. 2014;46(10):1135–9.CrossRefGoogle Scholar
  6. 6.
    Khameneh HJ, Mortellaro A. NLRC4 gets out of control. Nat Genet. 2014;46(10):1048–9.CrossRefGoogle Scholar
  7. 7.
    Zhu G, Chen J, Tian J, Ge L, Xing A, Tang G. Expression of NLRC4 in children with septicaemia and mechanisms of NLRC4 in in vitro cytokine secretion. Mol Med Rep. 2016;14(1):509–14.CrossRefGoogle Scholar
  8. 8.
    Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B, Liu Y, DiMattia MA, Zaal KJ, Sanchez GA, Kim H, Chapelle D, Plass N, Huang Y, Villarino AV, Biancotto A, Fleisher TA, Duncan JA, O'Shea JJ, Benseler S, Grom A, Deng Z, Laxer RM, Goldbach-Mansky R. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014;46(10):1140–6.CrossRefGoogle Scholar
  9. 9.
    Romberg N, Vogel TP, Canna SW. NLRC4 inflammasomopathies. Curr Opin Allergy Clin Immunol. 2017;17(6):398–404.CrossRefGoogle Scholar
  10. 10.
    Canna SW, Girard C, Malle L, de Jesus A, Romberg N, Kelsen J, Surrey LF, Russo P, Sleight A, Schiffrin E, Gabay C, Goldbach-Mansky R, Behrens EM. Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. J Allergy Clin Immunol. 2017;139(5):1698–701.CrossRefGoogle Scholar
  11. 11.
    Liang J, Alfano DN, Squires JE, Riley MM, Parks WT, Kofler J, El-Gharbawy A, Madan-Kheterpal S, Acquaro R, Picarsic J. Novel NLRC4 mutation causes a syndrome of perinatal autoinflammation with hemophagocytic lymphohistiocytosis, hepatosplenomegaly, fetal thrombotic vasculopathy, and congenital anemia and ascites. Pediatr Dev Pathol. 2017;20(6):498–505.CrossRefGoogle Scholar
  12. 12.
    Kitamura A, Sasaki Y, Abe T, Kano H, Yasutomo K. An inherited mutation in NLRC4 causes autoinflammation in human and mice. J Exp Med. 2014;211(12):2385–96.CrossRefGoogle Scholar
  13. 13.
    Volker-Touw CM, de Koning HD, Giltay JC, de Kovel CG, van Kempen TS, Oberndorff KM, Boes ML, van Steensel MA, van Well GT, Blokx WA, Schalkwijk J, Simon A, Frenkel J, van Gijn ME. Erythematous nodes, urticarial rash and arthralgias in a large pedigree with NLRC4-related autoinflammatory disease, expansion of the phenotype. Br J Dermatol. 2017;176(1):244–8.CrossRefGoogle Scholar
  14. 14.
    Kawasaki Y, Oda H, Ito J, Niwa A, Tanaka T, Hijikata A, Seki R, Nagahashi A, Osawa M, Asaka I, Watanabe A, Nishimata S, Shirai T, Kawashima H, Ohara O, Nakahata T, Nishikomori R, Heike T, Saito MK. Identification of a high-frequency somatic NLRC4 mutation as a cause of autoinflammation by pluripotent cell-based phenotype dissection. Arthritis Rheumatol (Hoboken, NJ). 2017;69(2):447–59.CrossRefGoogle Scholar
  15. 15.
    Sleptsova TVAEI, Savost’yanov KV, Pushkov AA, Bzarova TM, Valieva SI, Lomakina OL, Denisova RV, Isaeva KB, Chistyakova EGE. Experience of the successful treatment with canakinumab of a patient with NLPC4-associated autoinflammatory syndrome with enterocolitis. Pediatr Pharmacol. 2016;13(2):143–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Tania Siahanidou
    • 1
  • Sofia Tantou
    • 2
  • Maria Kanariou
    • 2
  1. 1.First Department of PediatricsNational & Kapodistrian University of Athens, “Aghia Sophia” Children’s HospitalAthensGreece
  2. 2.Department of Immunology-HistocompatibilitySpecialized Center & Referral Center for Primary Immunodeficiencies, Pediatric Immunology, “Aghia Sophia” Children’s HospitalAthensGreece

Personalised recommendations